ASXL3Additional sex combs like 3 (Drosophila)
Autism Reports / Total Reports
26 / 51Rare Variants / Common Variants
110 / 0Aliases
ASXL3, KIAA1713Associated Syndromes
Bainbridge-Ropers syndrome, Bainbridge-Ropers syndrome, ASD, DD, ID, Bainbridge-Ropers syndrome, DD, epilepsy/seizuresChromosome Band
18q12.1Associated Disorders
DD/NDD, ID, EP, EPS, ASDGenetic Category
Rare Single Gene Mutation, SyndromicRelevance to Autism
Four de novo loss-of-function (LoF) variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760, 28263302). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720, 27901041). Balasubramanian et al., 2017 reported 12 new patients with de novo heterozygous loss-of-function variants in ASXL3 and a diagnosis of Bainbridge-Ropers syndrome; nine of these patients were either formally diagnosed with autism or ASD, or were described as having autistic features (PMID 28100473). A de novo likely gene-disruptive variant in ASXL3 was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019; a meta-analysis of de novo variants in 4773 published ASD trios and 465 SPARK trios using TADA in the same report identified ASXL3 as an ASD candidate gene with a false discovery rate (FDR) 0.01. A detailed clinical and molecular analysis of 45 previously unpublished individuals with ASXL3-related syndrome in Schirwani et al., 2021 found that a diagnosis of autism spectrum disorder was made in 30% of individuals, and autistic traits including stereotypies, poor eye contact, hand flapping, rocking, and head shaking were present in the majority of individuals. A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified ASXL3 as a gene reaching exome-wide significance (P < 2.5E-06).
Molecular Function
Putative Polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development. PcG proteins are not required to initiate repression, but to maintain it during later stages of development. They probably act via methylation of histones, rendering chromatin heritably changed in its expressibility. Heterozygous de novo truncating variants in this gene were recently identified in patients with a novel clinical phenotype similar to Bohring-Opitz syndrome (Bainbridge et al., 2013).
External Links
SFARI Genomic Platforms
Reports related to ASXL3 (51 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Recent Recommendation | De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome | Bainbridge MN , et al. (2013) | No | ID |
2 | Primary | De novo frameshift mutation in ASXL3 in a patient with global developmental delay, microcephaly, and craniofacial anomalies | Dinwiddie DL , et al. (2013) | Yes | DD |
3 | Recent Recommendation | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
4 | Recent Recommendation | Low load for disruptive mutations in autism genes and their biased transmission | Iossifov I , et al. (2015) | Yes | - |
5 | Support | De novo dominant ASXL3 mutations alter H2A deubiquitination and transcription in Bainbridge-Ropers syndrome | Srivastava A , et al. (2015) | No | DD, ID |
6 | Support | Novel splicing mutation in the ASXL3 gene causing Bainbridge-Ropers syndrome | Hori I , et al. (2016) | No | ASD, DD |
7 | Support | Bainbridge-Ropers syndrome caused by loss-of-function variants in ASXL3: a recognizable condition | Kuechler A , et al. (2016) | No | ID |
8 | Recent Recommendation | Delineating the phenotypic spectrum of Bainbridge-Ropers syndrome: 12 new patients with de novo, heterozygous, loss-of-function mutations in ASXL3 and review of published literature | Balasubramanian M , et al. (2017) | No | ID, ASD or autistic features |
9 | Support | Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder | C Yuen RK et al. (2017) | Yes | - |
10 | Support | A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology | Vissers LE , et al. (2017) | No | - |
11 | Support | Global developmental delay and postnatal microcephaly: Bainbridge-Ropers syndrome with a new mutation in ASXL3 | Contreras-Capetillo SN , et al. (2017) | No | DD, microcephaly |
12 | Support | Genomic diagnosis for children with intellectual disability and/or developmental delay | Bowling KM , et al. (2017) | Yes | - |
13 | Support | Novel compound heterozygous ASXL3 mutation causing Bainbridge-ropers like syndrome and primary IGF1 deficiency | Giri D , et al. (2017) | No | ASD, DD |
14 | Support | Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders | Li J , et al. (2017) | Yes | - |
15 | Support | Exome sequencing reveals NAA15 and PUF60 as candidate genes associated with intellectual disability | Zhao JJ , et al. (2017) | Yes | Hypotonia, dysmorphic features |
16 | Support | A de novo nonsense mutation in ASXL3 shared by siblings with Bainbridge-Ropers syndrome | Koboldt DC , et al. (2018) | No | DD, ID, epilepsy/seizures, autistic features |
17 | Support | Phenotypic characterization of an older adult male with late-onset epilepsy and a novel mutation in ASXL3 shows overlap with the associated Bainbridge-Ropers syndrome | Verhoeven W , et al. (2018) | No | Autistic features, behavioral abnormalities |
18 | Support | Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model | Guo H , et al. (2018) | Yes | - |
19 | Support | Neurological Diseases With Autism Spectrum Disorder: Role of ASD Risk Genes | Xiong J , et al. (2019) | Yes | ID |
20 | Support | Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort | Callaghan DB , et al. (2019) | Yes | - |
21 | Support | Novel de novo frameshift variant in the ASXL3 gene in a child with microcephaly and global developmental delay | Wayhelova M , et al. (2019) | No | DD, ID, microcephaly, autistic features |
22 | Support | Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks | Ruzzo EK , et al. (2019) | Yes | - |
23 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
24 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
25 | Support | Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use | Husson T , et al. (2020) | Yes | - |
26 | Support | Bainbridge-ropers syndrome caused by loss-of-function variants in ASXL3: Clinical abnormalities, medical imaging features, and gene variation in infancy of case report | Yang L et al. (2020) | No | - |
27 | Support | Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders | Wang T et al. (2020) | Yes | - |
28 | Support | - | Li JR et al. (2020) | Yes | - |
29 | Support | - | Taà Ÿkñran EZ et al. (2021) | No | Epilepsy/seizures, autistic features |
30 | Support | - | Schirwani S et al. (2021) | No | ASD |
31 | Support | - | Mahjani B et al. (2021) | Yes | - |
32 | Support | - | Aguilera C et al. (2021) | No | Stereotypy |
33 | Support | - | Chen S et al. (2021) | Yes | DD, ID |
34 | Support | - | Wu K et al. (2021) | No | Autistic features |
35 | Support | - | Khan TR et al. (2022) | No | Autistic features |
36 | Support | - | Gerges P et al. (2022) | Yes | - |
37 | Support | - | Verberne EA et al. (2022) | No | - |
38 | Support | - | Brea-Fernández AJ et al. (2022) | No | - |
39 | Support | - | Hu C et al. (2022) | Yes | - |
40 | Support | - | Zhou X et al. (2022) | Yes | - |
41 | Support | - | Miyake N et al. (2023) | Yes | - |
42 | Support | - | Spataro N et al. (2023) | Yes | - |
43 | Support | - | Hu C et al. (2023) | Yes | DD, ID |
44 | Support | - | Wang J et al. (2023) | Yes | - |
45 | Support | - | Bartolomaeus T et al. (2023) | No | - |
46 | Support | - | Cirnigliaro M et al. (2023) | Yes | - |
47 | Support | - | Sanchis-Juan A et al. (2023) | No | - |
48 | Support | - | Amerh S Alqahtani et al. (2023) | No | - |
49 | Support | - | Maya C Ayoub et al. (2023) | No | - |
50 | Support | - | Tamam Khalaf et al. (2024) | No | - |
51 | Support | - | Axel Schmidt et al. (2024) | No | Epilepsy/seizures |
Rare Variants (110)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.4360C>T | p.Gln1454Ter | stop_gained | De novo | - | - | 37007974 | Hu C et al. (2023) | |
c.1083-1G>A | - | splice_site_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.2801T>G | p.Leu934Ter | stop_gained | De novo | - | - | 33004838 | Wang T et al. (2020) | |
c.3039+1G>A | - | splice_site_variant | De novo | - | - | 27075689 | Hori I , et al. (2016) | |
c.3106C>T | p.Arg1036Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.3364C>T | p.Gln1122Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.4144C>T | p.Gln1382Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.4322C>G | p.Ser1441Ter | stop_gained | De novo | - | - | 33004838 | Wang T et al. (2020) | |
c.1612G>T | p.Glu538Ter | stop_gained | De novo | - | - | 35172777 | Khan TR et al. (2022) | |
c.3039+1G>T | - | splice_site_variant | Unknown | - | - | 35253369 | Verberne EA et al. (2022) | |
c.3106C>T | p.Arg1036Ter | stop_gained | De novo | - | - | 34653234 | Aguilera C et al. (2021) | |
c.1369G>T | p.Glu457Ter | stop_gained | De novo | - | - | 27901041 | Kuechler A , et al. (2016) | |
c.1682C>A | p.Ser561Ter | stop_gained | Unknown | - | - | 28554332 | Bowling KM , et al. (2017) | |
c.3043C>T | p.Gln1015Ter | stop_gained | De novo | - | Simplex | 34886823 | Wu K et al. (2021) | |
c.1795G>T | p.Glu599Ter | stop_gained | De novo | - | Simplex | 33392332 | Li JR et al. (2020) | |
c.6647G>A | p.Arg2216Gln | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.3106C>T | p.Arg1036Ter | stop_gained | De novo | - | - | 27901041 | Kuechler A , et al. (2016) | |
c.3613G>T | p.Glu1205Ter | stop_gained | De novo | - | - | 27901041 | Kuechler A , et al. (2016) | |
c.1669G>T | p.Glu557Ter | stop_gained | Unknown | - | - | 39039281 | Axel Schmidt et al. (2024) | |
c.1570G>T | p.Glu524Ter | stop_gained | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
c.5467C>T | p.Arg1823Ter | stop_gained | Unknown | - | - | 38438125 | Tamam Khalaf et al. (2024) | |
c.3777T>C | p.Asp1259%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.5467C>T | p.Arg1823Ter | stop_gained | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
c.4399C>T | p.Arg1467Ter | stop_gained | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
c.3364C>T | p.Gln1122Ter | stop_gained | De novo | - | - | 26647312 | Srivastava A , et al. (2015) | |
c.1210C>T | p.Gln404Ter | stop_gained | De novo | - | - | 23383720 | Bainbridge MN , et al. (2013) | |
c.1396C>T | p.Gln466Ter | stop_gained | De novo | - | - | 23383720 | Bainbridge MN , et al. (2013) | |
c.169A>G | p.Met57Val | missense_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
c.4906C>T | p.Gln1636Ter | stop_gained | De novo | - | Simplex | 28263302 | C Yuen RK et al. (2017) | |
c.6640T>C | p.Ser2214Pro | missense_variant | Unknown | - | - | 28554332 | Bowling KM , et al. (2017) | |
c.1074T>A | p.Tyr358Ter | stop_gained | De novo | - | - | 28100473 | Balasubramanian M , et al. (2017) | |
c.1783C>T | p.Gln595Ter | stop_gained | De novo | - | - | 28100473 | Balasubramanian M , et al. (2017) | |
c.3136G>A | p.Gly1046Arg | missense_variant | Familial | Maternal | - | 35741772 | Hu C et al. (2022) | |
c.5695C>T | p.Arg1899Trp | missense_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
c.3526C>T | p.Arg1176Trp | missense_variant | Unknown | - | Simplex | 33004838 | Wang T et al. (2020) | |
c.3635T>G | p.Leu1212Ter | stop_gained | De novo | - | - | 28100473 | Balasubramanian M , et al. (2017) | |
c.4144C>T | p.Gln1382Ter | stop_gained | De novo | - | - | 28100473 | Balasubramanian M , et al. (2017) | |
c.4330C>T | p.Arg1444Ter | stop_gained | De novo | - | - | 28100473 | Balasubramanian M , et al. (2017) | |
c.3833del | p.Asn1278IlefsTer2 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.3493_3494deTG | p.Cys1165Ter | frameshift_variant | De novo | - | - | 32517662 | Yang L et al. (2020) | |
c.3106C>T | p.Arg1036Ter | stop_gained | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.3178C>T | p.Arg1060Trp | missense_variant | Familial | Maternal | - | 33004838 | Wang T et al. (2020) | |
c.5560G>A | p.Val1854Ile | missense_variant | Unknown | - | Simplex | 35205231 | Gerges P et al. (2022) | |
c.3737C>A | p.Ser1246Ter | stop_gained | De novo | - | Not simplex | 32094338 | Husson T , et al. (2020) | |
c.3106C>T | p.Arg1036Ter | stop_gained | De novo | - | Multiplex | 29305346 | Koboldt DC , et al. (2018) | |
c.1083-1G>A | - | splice_site_variant | De novo | - | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
c.1422dup | p.Glu475Ter | frameshift_variant | De novo | - | - | 23383720 | Bainbridge MN , et al. (2013) | |
c.3106C>T | p.Arg1036Ter | stop_gained | De novo | - | - | 35322241 | Brea-Fernández AJ et al. (2022) | |
c.4399C>T | p.Arg1467Ter | stop_gained | De novo | - | - | 35322241 | Brea-Fernández AJ et al. (2022) | |
c.182A>T | p.Asn61Ile | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
c.274G>A | p.Gly92Ser | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
c.3464C>A | p.Ser1155Ter | stop_gained | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
c.4400_4403dup | p.Pro1470AsnfsTer4 | frameshift_variant | De novo | - | - | 37007974 | Hu C et al. (2023) | |
c.1311_1315dup | p.Ser439TrpfsTer7 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.1219del | p.Ser407AlafsTer2 | frameshift_variant | De novo | - | - | 27901041 | Kuechler A , et al. (2016) | |
c.3494_3495del | p.Cys1165Ter | frameshift_variant | De novo | - | - | 27901041 | Kuechler A , et al. (2016) | |
c.2153C>T | p.Pro718Leu | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
c.2923T>G | p.Cys975Gly | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
c.1579C>T | p.Gln527Ter | stop_gained | Unknown | - | Simplex | 37799141 | Amerh S Alqahtani et al. (2023) | |
c.1118_1128dup | p.Asn377LeufsTer36 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.1982_1985del | p.Lys661ThrfsTer15 | frameshift_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
c.3753_3756del | p.Glu1251AspfsTer4 | frameshift_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
c.1897_1898del | p.Gln633ValfsTer13 | frameshift_variant | De novo | - | - | 34800434 | Chen S et al. (2021) | |
c.4466T>A | p.Val1489Asp | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
c.6374A>G | p.Tyr2125Cys | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
c.1491dup | p.Asn498Ter | frameshift_variant | De novo | - | - | 28100473 | Balasubramanian M , et al. (2017) | |
c.6200_6201del | p.Leu2067GlnfsTer10 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.2094dup | p.Pro699ThrfsTer5 | frameshift_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
c.4330C>T | p.Arg1444Ter | stop_gained | Unknown | Not maternal | - | 26647312 | Srivastava A , et al. (2015) | |
c.1448dup | p.Thr484AsnfsTer5 | frameshift_variant | De novo | - | - | 26647312 | Srivastava A , et al. (2015) | |
c.1897_1898del | p.Gln633ValfsTer13 | frameshift_variant | De novo | - | - | 31031587 | Xiong J , et al. (2019) | |
c.3006del | p.Arg1004GlufsTer21 | frameshift_variant | De novo | - | - | 31180560 | Wayhelova M , et al. (2019) | |
c.2965C>T | p.Arg989Trp | missense_variant | Familial | Maternal | Simplex | 28785287 | Giri D , et al. (2017) | |
c.1088del | p.Gly363AlafsTer8 | frameshift_variant | De novo | - | Simplex | 36973392 | Miyake N et al. (2023) | |
c.4890_4893del | p.Lys1631AsnfsTer3 | frameshift_variant | De novo | - | - | 36980980 | Spataro N et al. (2023) | |
c.3078G>C | p.Lys1026Asn | missense_variant | Familial | Paternal | Simplex | 28785287 | Giri D , et al. (2017) | |
c.4211_4212del | p.Thr1404ArgfsTer23 | frameshift_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
c.4072_4073del | p.Val1358LeufsTer8 | frameshift_variant | De novo | - | - | 27901041 | Kuechler A , et al. (2016) | |
c.1485_1488dup | p.Asp497Ter | frameshift_variant | De novo | - | - | 28100473 | Balasubramanian M , et al. (2017) | |
c.4219_4220del | p.Leu1407GlyfsTer20 | frameshift_variant | De novo | - | - | 28333917 | Vissers LE , et al. (2017) | |
c.5970_5973dup | p.Pro1992IlefsTer10 | frameshift_variant | De novo | - | - | 31452935 | Feliciano P et al. (2019) | |
c.3827_3830dup | p.Asn1278LeufsTer2 | frameshift_variant | De novo | - | - | 39039281 | Axel Schmidt et al. (2024) | |
c.4839_4890del | p.Met1614LysfsTer4 | frameshift_variant | De novo | - | - | 39039281 | Axel Schmidt et al. (2024) | |
c.1201del | p.Ala401GlnfsTer8 | frameshift_variant | De novo | - | - | 28100473 | Balasubramanian M , et al. (2017) | |
c.4172_4173del | p.Val1391GlufsTer8 | frameshift_variant | De novo | - | Simplex | 30564305 | Guo H , et al. (2018) | |
c.4143dup | p.Gln1382ThrfsTer18 | frameshift_variant | De novo | - | Multiplex | 28990276 | Zhao JJ , et al. (2017) | |
c.1082dup | p.Leu362AlafsTer23 | frameshift_variant | De novo | - | - | 28100473 | Balasubramanian M , et al. (2017) | |
c.3355dup | p.His1119ProfsTer7 | frameshift_variant | De novo | - | - | 28100473 | Balasubramanian M , et al. (2017) | |
c.2396C>T | p.Ser799Phe | missense_variant | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.2773C>G | p.His925Asp | missense_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.4170dup | p.Val1391CysfsTer9 | frameshift_variant | De novo | - | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.1978_1981del | p.Asp660AsnfsTer16 | frameshift_variant | De novo | - | - | 23383720 | Bainbridge MN , et al. (2013) | |
c.3178dup | p.Arg1060ProfsTer50 | frameshift_variant | De novo | - | - | 28100473 | Balasubramanian M , et al. (2017) | |
c.4180_4181del | p.Ala1394ProfsTer5 | frameshift_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
c.3407A>G | p.Lys1136Arg | missense_variant | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.4817G>A | p.Arg1606Gln | missense_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.5309G>A | p.Gly1770Glu | missense_variant | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.5468G>A | p.Arg1823Gln | missense_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.6724G>T | p.Val2242Leu | missense_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
c.4376del | p.Gly1459AlafsTer7 | frameshift_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
c.6737T>C | p.Val2246Ala | missense_variant | Familial | Paternal | Multiplex | 25363760 | De Rubeis S , et al. (2014) | |
c.1627_1628del | p.Leu543TyrfsTer12 | frameshift_variant | De novo | - | - | 33739554 | Taà Ÿkñran EZ et al. (2021) | |
c.3127_3128dup | p.Gly1045ValfsTer99 | frameshift_variant | De novo | - | - | 28100473 | Balasubramanian M , et al. (2017) | |
c.1897_1898del | p.Gln633ValfsTer13 | frameshift_variant | De novo | - | Simplex | 24044690 | Dinwiddie DL , et al. (2013) | |
c.704dup | p.Ser236ValfsTer12 | frameshift_variant | Familial | Paternal | Multiplex | 31398340 | Ruzzo EK , et al. (2019) | |
c.6697_6710dup | p.Ser2238ThrfsTer3 | frameshift_variant | Unknown | - | Multiplex | 29628764 | Verhoeven W , et al. (2018) | |
c.4888_4892del | p.Gln1630ArgfsTer14 | frameshift_variant | Unknown | - | Simplex | 31038196 | Callaghan DB , et al. (2019) | |
c.2992_2995del | p.Glu998LysfsTer26 | frameshift_variant | De novo | - | - | 28431838 | Contreras-Capetillo SN , et al. (2017) | |
c.5092_5096delinsTACAACAAACTCCGG | p.Gly1698TyrfsTer7 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.4462_4465del | p.Thr1488SerfsTer17 | frameshift_variant | Familial | Paternal | Multiplex | 37460657 | Bartolomaeus T et al. (2023) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence, Syndromic
Score Delta: Score remained at 1S
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
4/1/2021
Score remained at 1
Description
Four de novo loss-of-function (LoF) variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760, 28263302). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720, 27901041). Balasubramanian et al., 2017 reported 12 new patients with de novo heterozygous loss-of-function variants in ASXL3 and a diagnosis of Bainbridge-Ropers syndrome; nine of these patients were either formally diagnosed with autism or ASD, or were described as having autistic features (PMID 28100473).
1/1/2021
Score remained at 1
Description
Four de novo loss-of-function (LoF) variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760, 28263302). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720, 27901041). Balasubramanian et al., 2017 reported 12 new patients with de novo heterozygous loss-of-function variants in ASXL3 and a diagnosis of Bainbridge-Ropers syndrome; nine of these patients were either formally diagnosed with autism or ASD, or were described as having autistic features (PMID 28100473).
10/1/2020
Score remained at 1
Description
Four de novo loss-of-function (LoF) variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760, 28263302). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720, 27901041). Balasubramanian et al., 2017 reported 12 new patients with de novo heterozygous loss-of-function variants in ASXL3 and a diagnosis of Bainbridge-Ropers syndrome; nine of these patients were either formally diagnosed with autism or ASD, or were described as having autistic features (PMID 28100473).
7/1/2020
Score remained at 1
Description
Four de novo loss-of-function (LoF) variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760, 28263302). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720, 27901041). Balasubramanian et al., 2017 reported 12 new patients with de novo heterozygous loss-of-function variants in ASXL3 and a diagnosis of Bainbridge-Ropers syndrome; nine of these patients were either formally diagnosed with autism or ASD, or were described as having autistic features (PMID 28100473).
1/1/2020
Score remained at 1
Description
Four de novo loss-of-function (LoF) variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760, 28263302). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720, 27901041). Balasubramanian et al., 2017 reported 12 new patients with de novo heterozygous loss-of-function variants in ASXL3 and a diagnosis of Bainbridge-Ropers syndrome; nine of these patients were either formally diagnosed with autism or ASD, or were described as having autistic features (PMID 28100473).
10/1/2019
Score remained at 1
New Scoring Scheme
Description
Four de novo loss-of-function (LoF) variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760, 28263302). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720, 27901041). Balasubramanian et al., 2017 reported 12 new patients with de novo heterozygous loss-of-function variants in ASXL3 and a diagnosis of Bainbridge-Ropers syndrome; nine of these patients were either formally diagnosed with autism or ASD, or were described as having autistic features (PMID 28100473).
7/1/2019
Score remained at 1S
Description
Four de novo loss-of-function (LoF) variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760, 28263302). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720, 27901041). Balasubramanian et al., 2017 reported 12 new patients with de novo heterozygous loss-of-function variants in ASXL3 and a diagnosis of Bainbridge-Ropers syndrome; nine of these patients were either formally diagnosed with autism or ASD, or were described as having autistic features (PMID 28100473).
4/1/2019
Score remained at 1S
Description
Four de novo loss-of-function (LoF) variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760, 28263302). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720, 27901041). Balasubramanian et al., 2017 reported 12 new patients with de novo heterozygous loss-of-function variants in ASXL3 and a diagnosis of Bainbridge-Ropers syndrome; nine of these patients were either formally diagnosed with autism or ASD, or were described as having autistic features (PMID 28100473).
1/1/2019
Score remained at 1S
Description
Four de novo loss-of-function (LoF) variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760, 28263302). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720, 27901041). Balasubramanian et al., 2017 reported 12 new patients with de novo heterozygous loss-of-function variants in ASXL3 and a diagnosis of Bainbridge-Ropers syndrome; nine of these patients were either formally diagnosed with autism or ASD, or were described as having autistic features (PMID 28100473).
10/1/2017
Score remained at 1S
Description
Four de novo loss-of-function (LoF) variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760, 28263302). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01 < FDR ? 0.05, meaning that this gene had a ? 95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720, 27901041). Balasubramanian et al., 2017 reported 12 new patients with de novo heterozygous loss-of-function variants in ASXL3 and a diagnosis of Bainbridge-Ropers syndrome; nine of these patients were either formally diagnosed with autism or ASD, or were described as having autistic features (PMID 28100473).
7/1/2017
Score remained at 1S
Description
Four de novo loss-of-function (LoF) variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760, 28263302). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01 < FDR ? 0.05, meaning that this gene had a ? 95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720, 27901041). Balasubramanian et al., 2017 reported 12 new patients with de novo heterozygous loss-of-function variants in ASXL3 and a diagnosis of Bainbridge-Ropers syndrome; nine of these patients were either formally diagnosed with autism or ASD, or were described as having autistic features (PMID 28100473).
4/1/2017
Score remained at 1S
Description
Three de novo LoF variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01< FDR ?0.05, meaning that this gene had a ?95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Balasubramanian et al., 2017 reported 12 new patients with de novo heterozygous loss-of-function variants in ASXL3 and a diagnosis of Bainbridge-Ropers syndrome; nine of these patients were either formally diagnosed with autism or ASD, or were described as having autistic features.
Reports Added
[De novo frameshift mutation in ASXL3 in a patient with global developmental delay, microcephaly, and craniofacial anomalies.2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome.2013] [De novo Dominant ASXL3 Mutations Alter H2A Deubiquitination and Transcription in Bainbridge-Ropers Syndrome.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Novel splicing mutation in the ASXL3 gene causing Bainbridge-Ropers syndrome.2016] [Bainbridge-Ropers syndrome caused by loss-of-function variants in ASXL3: a recognizable condition.2016] [Delineating the phenotypic spectrum of Bainbridge-Ropers syndrome: 12 new patients with de novo, heterozygous, loss-of-function mutations in ASXL3 ...2017] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017] [A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.2017] [Global developmental delay and postnatal microcephaly: Bainbridge-Ropers syndrome with a new mutation in ASXL3.2017] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]1/1/2017
Score remained at 1S
Description
Three de novo LoF variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01 < FDR ?0.05, meaning that this gene had a ?95% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Balasubramanian et al., 2017 reported 12 new patients with de novo heterozygous loss-of-function variants in ASXL3 and a diagnosis of Bainbridge-Ropers syndrome; nine of these patients were either formally diagnosed with autism or ASD, or were described as having autistic features.
10/1/2016
Score remained at 1S
Description
Three de novo LoF variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01
4/1/2016
Score remained at 1S
Description
Three de novo LoF variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01
Reports Added
[De novo frameshift mutation in ASXL3 in a patient with global developmental delay, microcephaly, and craniofacial anomalies.2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome.2013] [De novo Dominant ASXL3 Mutations Alter H2A Deubiquitination and Transcription in Bainbridge-Ropers Syndrome.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Novel splicing mutation in the ASXL3 gene causing Bainbridge-Ropers syndrome.2016]1/1/2016
Score remained at 1S
Description
Three de novo LoF variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01
Reports Added
[De novo frameshift mutation in ASXL3 in a patient with global developmental delay, microcephaly, and craniofacial anomalies.2013] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome.2013] [De novo Dominant ASXL3 Mutations Alter H2A Deubiquitination and Transcription in Bainbridge-Ropers Syndrome.2015] [Low load for disruptive mutations in autism genes and their biased transmission.2015]10/1/2014
Increased from to 1S
Description
Three de novo LoF variants in the ASXL3 gene have been identified in ASD probands (PMIDs 24044690, 25363760). De novo truncating variants in this gene have also been identified in individuals presenting with a syndrome that shares characteristics with Bohring-Opitz syndrome, including developmental delay, post-natal growth retardation and feeding problems (PMID 23383720). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified ASXL3 as a gene meeting high statistical significance with a 0.01
Krishnan Probability Score
Score 0.49389101063994
Ranking 3932/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.99997704847346
Ranking 523/18225 scored genes
[Show Scoring Methodology]
Iossifov Probability Score
Score 0.976
Ranking 46/239 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.10499768511766
Ranking 67/18665 scored genes
[Show Scoring Methodology]
Larsen Cumulative Evidence Score
Score 47
Ranking 37/461 scored genes
[Show Scoring Methodology]
Zhang D Score
Score 0.42624965938137
Ranking 1163/20870 scored genes
[Show Scoring Methodology]
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
---|---|---|---|---|---|
BAP1 | BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) | Human | Protein Binding | 8314 | Q92560 |