HNRNPUheterogeneous nuclear ribonucleoprotein U
Autism Reports / Total Reports
11 / 41Rare Variants / Common Variants
129 / 0Aliases
HNRNPU, EIEE54-AS1, HNRPU, SAF-A, SAFA, U21.1, hnRNP U, pp120, HNRNPUAssociated Syndromes
-Chromosome Band
1q44Associated Disorders
DD/NDD, ID, EP, EPS, ASDGenetic Category
Rare Single Gene Mutation, Syndromic, FunctionalRelevance to Autism
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017).
Molecular Function
This gene encodes a member of a family of proteins that bind nucleic acids and function in the formation of ribonucleoprotein complexes in the nucleus with heterogeneous nuclear RNA (hnRNA). The encoded protein has affinity for both RNA and DNA, and binds scaffold-attached region (SAR) DNA. Mutations in this gene have been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391).
External Links
SFARI Genomic Platforms
Reports related to HNRNPU (41 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Support | Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 | Carvill GL , et al. (2013) | No | ID, epilepsy/seizures |
2 | Support | De novo mutations in epileptic encephalopathies | Epi4K Consortium , et al. (2013) | No | ID, epilepsy/seizures, ASD |
3 | Support | De novo mutations in moderate or severe intellectual disability | Hamdan FF , et al. (2014) | No | ID, epilepsy/seizures, autistic features |
4 | Support | - | Zhu X et al. (2015) | No | - |
5 | Support | Targeted sequencing of 351 candidate genes for epileptic encephalopathy in a large cohort of patients | de Kovel CG , et al. (2016) | No | ID, epilepsy/seizures |
6 | Support | De novo genic mutations among a Chinese autism spectrum disorder cohort | Wang T , et al. (2016) | Yes | - |
7 | Support | Prevalence and architecture of de novo mutations in developmental disorders | et al. (2017) | No | - |
8 | Support | - | Depienne C et al. (2017) | No | ASD |
9 | Recent Recommendation | Heterozygous HNRNPU variants cause early onset epilepsy and severe intellectual disability | Bramswig NC , et al. (2017) | No | - |
10 | Support | Genomic diagnosis for children with intellectual disability and/or developmental delay | Bowling KM , et al. (2017) | Yes | - |
11 | Support | Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients | Chrot E , et al. (2017) | No | - |
12 | Primary | Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder | Lim ET , et al. (2017) | Yes | - |
13 | Support | Clinical and molecular characterization of de novo loss of function variants in HNRNPU | Leduc MS , et al. (2017) | No | ASD |
14 | Support | De novo mutations in HNRNPU result in a neurodevelopmental syndrome | Yates TM , et al. (2017) | No | Epilepsy/seizures, ASD |
15 | Support | HRPU-2, a Homolog of Mammalian hnRNP U, Regulates Synaptic Transmission by Controlling the Expression of SLO-2 Potassium Channel in Caenorhabditis elegans | Liu P , et al. (2017) | No | - |
16 | Support | - | Oates S et al. (2018) | No | - |
17 | Support | An episode of acute encephalopathy with biphasic seizures and late reduced diffusion followed by hemiplegia and intractable epilepsy observed in a patient with a novel frameshift mutation in HNRNPU | Shimada S , et al. (2018) | No | Epilepsy/seizures, DD, ID, autistic behavior, ster |
18 | Support | - | et al. (2019) | No | - |
19 | Support | - | Demos M et al. (2019) | Yes | - |
20 | Support | Clinical utility of multigene panel testing in adults with epilepsy and intellectual disability | Borlot F , et al. (2019) | No | Autistic features |
21 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
22 | Support | - | Fernández-Marmiesse A et al. (2019) | No | - |
23 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
24 | Support | Clinical findings of 21 previously unreported probands with HNRNPU-related syndrome and comprehensive literature review | Durkin A et al. (2020) | No | - |
25 | Support | - | Johannesen KM et al. (2020) | No | - |
26 | Support | Clinical and genetic characteristics of patients with Doose syndrome | Hinokuma N et al. (2020) | No | - |
27 | Support | Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders | Wang T et al. (2020) | Yes | - |
28 | Support | - | Brunet T et al. (2021) | No | - |
29 | Support | - | Gillentine MA et al. (2021) | No | ASD, DD |
30 | Support | - | Taylor J et al. (2022) | No | ASD or autistic features, OCD |
31 | Support | - | Chuan Z et al. (2022) | No | - |
32 | Support | - | Sapir T et al. (2022) | No | - |
33 | Support | - | Zhou X et al. (2022) | Yes | - |
34 | Support | - | Ressler AK et al. (2022) | No | - |
35 | Support | - | Rooney K et al. (2023) | No | ASD or autistic features, epilepsy/seizures |
36 | Support | - | Lee S et al. (2023) | Yes | ID |
37 | Support | - | Sanchis-Juan A et al. (2023) | No | - |
38 | Support | - | Sarah A Dugger et al. (2023) | No | - |
39 | Support | - | Francesca Mastropasqua et al. (2023) | No | - |
40 | Support | - | Tamam Khalaf et al. (2024) | Yes | - |
41 | Support | - | Erika Nicole Dreikorn et al. (2024) | Yes | - |
Rare Variants (129)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | copy_number_loss | De novo | - | - | 37120726 | Rooney K et al. (2023) | |
- | - | copy_number_loss | De novo | - | - | 31273778 | Borlot F , et al. (2019) | |
- | - | copy_number_gain | Unknown | - | - | 28393272 | Bramswig NC , et al. (2017) | |
- | - | copy_number_loss | De novo | - | Simplex | 35138025 | Taylor J et al. (2022) | |
c.1615-1G>A | - | splice_site_variant | De novo | - | - | 25590979 | Zhu X et al. (2015) | |
c.2365C>T | p.Arg789Ter | stop_gained | De novo | - | - | 37407733 | Lee S et al. (2023) | |
c.1681C>T | p.Gln561Ter | stop_gained | De novo | - | - | 33004838 | Wang T et al. (2020) | |
c.1714C>T | p.Arg572Ter | stop_gained | De novo | - | - | 33004838 | Wang T et al. (2020) | |
c.1852C>T | p.Gln618Ter | stop_gained | De novo | - | - | 33004838 | Wang T et al. (2020) | |
c.508C>T | p.Gln170Ter | stop_gained | De novo | - | - | 35138025 | Taylor J et al. (2022) | |
c.2425-2A>G | - | splice_site_variant | De novo | - | - | 35138025 | Taylor J et al. (2022) | |
c.878-9T>G | - | intron_variant | De novo | - | Simplex | 35138025 | Taylor J et al. (2022) | |
- | - | loss_of_function_variant | De novo | - | Simplex | 35138025 | Taylor J et al. (2022) | |
- | - | loss_of_function_variant | De novo | - | Unknown | 35138025 | Taylor J et al. (2022) | |
c.1060+1G>A | - | splice_site_variant | De novo | - | - | 28944577 | Yates TM , et al. (2017) | |
c.67C>T | p.Arg23Ter | stop_gained | Unknown | - | - | 28554332 | Bowling KM , et al. (2017) | |
c.1681C>T | p.Gln561Ter | stop_gained | De novo | - | - | 28283832 | Depienne C et al. (2017) | |
c.508C>T | p.Gln170Ter | stop_gained | De novo | - | - | 31452935 | Feliciano P et al. (2019) | |
c.2425-3C>A | - | splice_region_variant | De novo | - | - | 28283832 | Depienne C et al. (2017) | |
c.523C>T | p.Gln175Ter | stop_gained | De novo | - | - | 28393272 | Bramswig NC , et al. (2017) | |
c.817C>T | p.Gln273Ter | stop_gained | De novo | - | - | 28393272 | Bramswig NC , et al. (2017) | |
c.1569dup | p.Lys524Ter | frameshift_variant | De novo | - | - | 37407733 | Lee S et al. (2023) | |
c.1169A>C | p.Asn390Thr | missense_variant | Unknown | - | - | 35571021 | Chuan Z et al. (2022) | |
c.2219G>C | p.Gly740Ala | missense_variant | Unknown | - | - | 35571021 | Chuan Z et al. (2022) | |
c.893A>G | p.His298Arg | missense_variant | De novo | - | - | 35138025 | Taylor J et al. (2022) | |
c.67C>T | p.Arg23Ter | stop_gained | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.1450C>T | p.Arg484Ter | stop_gained | Unknown | - | - | 38438125 | Tamam Khalaf et al. (2024) | |
c.481C>T | p.Gln161Ter | stop_gained | Unknown | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.2425-2A>G | - | splice_site_variant | De novo | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.253dup | p.Glu85GlyfsTer60 | frameshift_variant | Unknown | - | - | 30951195 | et al. (2019) | |
c.692-1G>A | - | splice_site_variant | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.418G>A | p.Glu140Lys | missense_variant | De novo | - | - | 28944577 | Yates TM , et al. (2017) | |
c.1744-2del | - | splice_site_variant | Familial | Maternal | - | 33004838 | Wang T et al. (2020) | |
c.804-9_804-6del | - | splice_region_variant | De novo | - | - | 35138025 | Taylor J et al. (2022) | |
c.619C>T | p.Gln207Ter | stop_gained | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.575C>A | p.Ser192Ter | stop_gained | De novo | - | Unknown | 33619735 | Brunet T et al. (2021) | |
c.1686+1G>C | - | splice_site_variant | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.2365C>T | p.Arg789Ter | stop_gained | De novo | - | Multiplex | 33004838 | Wang T et al. (2020) | |
c.817C>T | p.Gln273Ter | stop_gained | De novo | - | Multiplex | 31164858 | Demos M et al. (2019) | |
c.1089G>A | p.Trp363Ter | stop_gained | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.1450C>T | p.Arg484Ter | stop_gained | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.1801C>T | p.Arg601Ter | stop_gained | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.960G>A | p.Trp320Ter | stop_gained | De novo | - | Simplex | 28944577 | Yates TM , et al. (2017) | |
c.1089G>A | p.Trp363Ter | stop_gained | De novo | - | Simplex | 28815871 | Leduc MS , et al. (2017) | |
c.1714C>T | p.Arg572Ter | stop_gained | De novo | - | Simplex | 28815871 | Leduc MS , et al. (2017) | |
c.511C>T | p.Gln171Ter | stop_gained | De novo | - | Simplex | 25356899 | Hamdan FF , et al. (2014) | |
c.970A>G | p.Arg324Gly | missense_variant | De novo | - | - | 28393272 | Bramswig NC , et al. (2017) | |
c.2140_2142del | p.Arg714del | inframe_deletion | Unknown | - | - | 29760947 | Oates S et al. (2018) | |
c.1088G>A | p.Trp363Ter | stop_gained | De novo | - | Multiplex | 32319732 | Durkin A et al. (2020) | |
c.1132T>C | p.Ser378Pro | missense_variant | De novo | - | - | 28393272 | Bramswig NC , et al. (2017) | |
c.325G>C | p.Glu109Gln | missense_variant | Unknown | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.1142A>G | p.Tyr381Cys | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
c.359C>T | p.Pro120Leu | missense_variant | De novo | - | Simplex | 28714951 | Lim ET , et al. (2017) | |
c.469G>C | p.Gly157Arg | missense_variant | De novo | - | Simplex | 28714951 | Lim ET , et al. (2017) | |
c.1720_1722del | p.Lys574del | inframe_deletion | De novo | - | - | 37120726 | Rooney K et al. (2023) | |
c.1368A>C | p.Glu456Asp | missense_variant | Unknown | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.1435G>A | p.Val479Ile | missense_variant | Unknown | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.1516C>T | p.Pro506Ser | missense_variant | Unknown | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.2199G>T | p.Arg733Ser | missense_variant | Unknown | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.2408A>G | p.Asn803Ser | missense_variant | Unknown | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.334dup | p.Ala112GlyfsTer33 | frameshift_variant | De novo | - | - | 33004838 | Wang T et al. (2020) | |
c.1142A>G | p.Tyr381Cys | missense_variant | De novo | - | - | 31981491 | Satterstrom FK et al. (2020) | |
- | - | complex_structural_alteration | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
c.1834G>A | p.Asp612Asn | missense_variant | Unknown | - | Simplex | 35138025 | Taylor J et al. (2022) | |
c.2425-2A>G | - | splice_site_variant | Unknown | - | - | 38846959 | Erika Nicole Dreikorn et al. (2024) | |
c.1211A>G | p.Asp404Gly | missense_variant | Familial | Paternal | - | 27824329 | Wang T , et al. (2016) | |
c.1507C>T | p.Pro522Ser | missense_variant | Familial | Paternal | - | 27824329 | Wang T , et al. (2016) | |
c.1624del | p.Gln542SerfsTer45 | frameshift_variant | De novo | - | - | 29760947 | Oates S et al. (2018) | |
c.1561dup | p.Ala521GlyfsTer4 | frameshift_variant | De novo | - | - | 35138025 | Taylor J et al. (2022) | |
c.2167+35_*4156del | p.? | copy_number_loss | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.878A>G | p.Tyr293Cys | missense_variant | De novo | - | Simplex | 32913952 | Hinokuma N et al. (2020) | |
c.16delinsATT | p.Val6IlefsTer4 | frameshift_variant | De novo | - | - | 28708303 | Chrot E , et al. (2017) | |
c.837_839del | p.Glu279del | inframe_deletion | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.2357G>A | p.Trp786Ter | stop_gained | Unknown | Not maternal | - | 23708187 | Carvill GL , et al. (2013) | |
c.1865_1867del | p.Glu622del | inframe_deletion | Unknown | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.1050_1051del | p.Thr351LysfsTer4 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.673_674del | p.Arg225GlyfsTer3 | frameshift_variant | De novo | - | - | 35138025 | Taylor J et al. (2022) | |
c.1868dup | p.Glu624ArgfsTer24 | frameshift_variant | De novo | - | - | 28283832 | Depienne C et al. (2017) | |
c.1755_1756insCCTCT | p.Ala586ProfsTer22 | frameshift_variant | De novo | - | - | 28135719 | et al. (2017) | |
c.906_907del | p.Asp304SerfsTer33 | frameshift_variant | De novo | - | - | 37120726 | Rooney K et al. (2023) | |
c.23del | p.Val8GlufsTer4 | frameshift_variant | De novo | - | Simplex | 28944577 | Yates TM , et al. (2017) | |
c.1755dup | p.Val586CysfsTer7 | frameshift_variant | De novo | - | - | 27652284 | de Kovel CG , et al. (2016) | |
c.2093dup | p.Asn698LysfsTer4 | frameshift_variant | Unknown | - | - | 38438125 | Tamam Khalaf et al. (2024) | |
c.29_30del | p.Lys10ThrfsTer17 | inframe_deletion | Unknown | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.198del | p.Ala67LeufsTer40 | frameshift_variant | De novo | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.596dup | p.Pro200AlafsTer24 | frameshift_variant | De novo | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.1812dup | p.Val605CysfsTer7 | frameshift_variant | Unknown | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.1863del | p.Phe621LeufsTer6 | frameshift_variant | Unknown | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.2085dup | p.Gly696TrpfsTer6 | frameshift_variant | Unknown | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.1665_1666del | p.Leu556AlafsTer12 | frameshift_variant | De novo | - | - | 35138025 | Taylor J et al. (2022) | |
c.2304_2305del | p.Gly769GlufsTer83 | frameshift_variant | De novo | - | - | 35138025 | Taylor J et al. (2022) | |
c.742dup | p.Arg248LysfsTer12 | frameshift_variant | De novo | - | Simplex | 35138025 | Taylor J et al. (2022) | |
c.1641del | p.Asp548IlefsTer5 | frameshift_variant | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.1243del | p.Asp415MetfsTer3 | frameshift_variant | De novo | - | Simplex | 35138025 | Taylor J et al. (2022) | |
c.76del | p.Ser26LeufsTer35 | frameshift_variant | De novo | - | Simplex | 29858110 | Shimada S , et al. (2018) | |
c.1957del | p.Glu653LysfsTer162 | frameshift_variant | De novo | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.1687-4_1692del | - | splice_site_variant | De novo | - | Simplex | 23934111 | Epi4K Consortium , et al. (2013) | |
c.1681del | p.Gln561SerfsTer45 | frameshift_variant | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.1836del | p.Tyr613IlefsTer11 | frameshift_variant | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.2299_2302del | p.Asn767GlufsTer66 | frameshift_variant | De novo | - | - | 28283832 | Depienne C et al. (2017) | |
c.149_156del | p.Arg50HisfsTer32 | frameshift_variant | De novo | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.815_820del | p.Thr273_Tyr274del | inframe_deletion | De novo | - | - | 31981491 | Satterstrom FK et al. (2020) | |
c.1571dup | p.Lys525GlufsTer25 | frameshift_variant | De novo | - | Simplex | 28944577 | Yates TM , et al. (2017) | |
c.1664del | p.Leu555ArgfsTer51 | frameshift_variant | De novo | - | Simplex | 28944577 | Yates TM , et al. (2017) | |
c.324_328del | p.Glu109ArgfsTer34 | frameshift_variant | De novo | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.547_560del | p.Ala183GlnfsTer36 | frameshift_variant | De novo | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.706_707del | p.Glu236ThrfsTer6 | frameshift_variant | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.847_857del | p.Phe283SerfsTer5 | frameshift_variant | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.395_401del | p.Asn132ThrfsTer63 | frameshift_variant | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.454_466del | p.Ala152ThrfsTer41 | frameshift_variant | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.2247_2248del | p.Gly750GlufsTer83 | frameshift_variant | De novo | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.2299_2302del | p.Asn767GlufsTer66 | frameshift_variant | Unknown | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.2304_2305del | p.Gly769GlufsTer83 | frameshift_variant | De novo | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.2319_2320del | p.Gly774TrpfsTer78 | frameshift_variant | De novo | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.712_715del | p.Lys238AlafsTer100 | frameshift_variant | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.1925_1926del | p.Leu642ProfsTer5 | frameshift_variant | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.2083_2084del | p.Ser695TrpfsTer6 | frameshift_variant | De novo | - | Simplex | 32319732 | Durkin A et al. (2020) | |
c.2213_2214del | p.Pro738ArgfsTer7 | frameshift_variant | De novo | - | Simplex | 35138025 | Taylor J et al. (2022) | |
c.1171_1172TG[1] | p.Cys391_Glu392delinsTer | stop_gained | De novo | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.1846_1847insCA | p.Arg616ThrfsTer9 | frameshift_variant | De novo | - | - | 33874999 | Gillentine MA et al. (2021) | |
c.651_660del | p.Gly218AlafsTer118 | frameshift_variant | De novo | - | Simplex | 28815871 | Leduc MS , et al. (2017) | |
c.2270_2271del | p.Pro757ArgfsTer7 | frameshift_variant | De novo | - | Simplex | 28815871 | Leduc MS , et al. (2017) | |
c.16delinsATT | p.Val6IlefsTer4 | frameshift_variant | Familial | Paternal | - | 28283832 | Depienne C et al. (2017) | |
c.2072del | p.Asn691IlefsTer143 | frameshift_variant | Unknown | Not maternal | - | 37120726 | Rooney K et al. (2023) | |
c.706_707del | p.Glu236ThrfsTer6 | frameshift_variant | De novo | - | Not simplex | 32319732 | Durkin A et al. (2020) | |
c.1367_1368insGA | p.Phe456LeufsTer8 | frameshift_variant | De novo | - | Simplex | 28944577 | Yates TM , et al. (2017) | |
c.1756_1757insGT | p.Val586GlyfsTer2 | frameshift_variant | Unknown | Not maternal | - | 33004838 | Wang T et al. (2020) | |
c.401_402del | p.Asp134GlyfsTer10 | frameshift_variant | De novo | - | - | 31780880 | Fernández-Marmiesse A et al. (2019) | |
c.914_916del | p.Arg305_Ala306delinsThr | inframe_indel | Unknown | Not paternal | - | 32427350 | Johannesen KM et al. (2020) |
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
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017; Yates et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder in Epi4K Consortium; Epilepsy Phenome/Genome Project 2013, Bramswig et al., 2017, Leduc et al., 2017, and Yates et al., 2017.
Reports Added
[Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios2015] [Prevalence and architecture of de novo mutations in developmental disorders2017] [Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU2017] [Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of two clinical units and 216 patients.2017] [Incorporating epilepsy genetics into clinical practice: a 360ðevaluation2018] [The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield2019] [Diagnostic Yield and Treatment Impact of Targeted Exome Sequencing in Early-Onset Epilepsy2019] [Rare Variants in 48 Genes Account for 42% of Cases of Epilepsy With or Without Neurodevelopmental Delay in 246 Pediatric Patients2019] [Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020] [Utility of genetic testing for therapeutic decision-making in adults with epilepsy2020] [Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders2021]1/1/2021
Score remained at 1
Description
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017; Yates et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder in Epi4K Consortium; Epilepsy Phenome/Genome Project 2013, Bramswig et al., 2017, Leduc et al., 2017, and Yates et al., 2017.
10/1/2020
Score remained at 1
Description
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017; Yates et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder in Epi4K Consortium; Epilepsy Phenome/Genome Project 2013, Bramswig et al., 2017, Leduc et al., 2017, and Yates et al., 2017.
4/1/2020
Score remained at 1
Description
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017; Yates et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder in Epi4K Consortium; Epilepsy Phenome/Genome Project 2013, Bramswig et al., 2017, Leduc et al., 2017, and Yates et al., 2017.
10/1/2019
Decreased from 4S to 1
New Scoring Scheme
Description
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017; Yates et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder in Epi4K Consortium; Epilepsy Phenome/Genome Project 2013, Bramswig et al., 2017, Leduc et al., 2017, and Yates et al., 2017.
7/1/2019
Decreased from 4S to 4S
Description
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017; Yates et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder in Epi4K Consortium; Epilepsy Phenome/Genome Project 2013, Bramswig et al., 2017, Leduc et al., 2017, and Yates et al., 2017.
7/1/2018
Decreased from 4S to 4S
Description
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017; Yates et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder in Epi4K Consortium; Epilepsy Phenome/Genome Project 2013, Bramswig et al., 2017, Leduc et al., 2017, and Yates et al., 2017.
7/1/2017
Increased from to 4S
Description
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder.
Krishnan Probability Score
Score 0.57111211166452
Ranking 825/25841 scored genes
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ExAC Score
Score 0.99990332258243
Ranking 673/18225 scored genes
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Sanders TADA Score
Score 0.7919757025084
Ranking 2076/18665 scored genes
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Zhang D Score
Score 0.38266856349508
Ranking 1654/20870 scored genes
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