SYNE1spectrin repeat containing, nuclear envelope 1
Autism Reports / Total Reports
17 / 24Rare Variants / Common Variants
44 / 2Aliases
SYNE1, 8B, CPG2, ARCA1, EDMD4, MYNE1, SCAR8Associated Syndromes
-Chromosome Band
6q25.2Associated Disorders
-Relevance to Autism
Rare mutations in the SYNE1 gene have been identified with autism (O'Roak et al., 2011) as well as with cerebellar ataxia and myogenic arthrogryposis multiplex congenita.
Molecular Function
Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization.
External Links
SFARI Genomic Platforms
Reports related to SYNE1 (24 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | Syne-1, a dystrophin- and Klarsicht-related protein associated with synaptic nuclei at the neuromuscular junction | Apel ED , et al. (2000) | No | - |
| 2 | Highly Cited | Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia | Gros-Louis F , et al. (2006) | No | - |
| 3 | Recent Recommendation | Mutation of SYNE-1, encoding an essential component of the nuclear lamina, is responsible for autosomal recessive arthrogryposis | Attali R , et al. (2009) | No | - |
| 4 | Recent Recommendation | SUN1/2 and Syne/Nesprin-1/2 complexes connect centrosome to the nucleus during neurogenesis and neuronal migration in mice | Zhang X , et al. (2009) | No | - |
| 5 | Primary | Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations | O'Roak BJ , et al. (2011) | Yes | - |
| 6 | Support | Association at SYNE1 in both bipolar disorder and recurrent major depression | Green EK , et al. (2012) | No | - |
| 7 | Recent Recommendation | Using whole-exome sequencing to identify inherited causes of autism | Yu TW , et al. (2013) | Yes | - |
| 8 | Positive Association | Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis | Cross-Disorder Group of the Psychiatric Genomics Consortium (2013) | Yes | - |
| 9 | Support | Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing | Jiang YH , et al. (2013) | Yes | - |
| 10 | Support | Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders | Cukier HN , et al. (2014) | Yes | - |
| 11 | Support | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
| 12 | Support | Excess of rare, inherited truncating mutations in autism | Krumm N , et al. (2015) | Yes | - |
| 13 | Support | Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease | Karaca E , et al. (2015) | No | Brain abnormalities, microcephaly |
| 14 | Support | Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability | Riazuddin S , et al. (2016) | No | - |
| 15 | Support | Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder | Krupp DR , et al. (2017) | Yes | - |
| 16 | Support | Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort | Wu H , et al. (2019) | Yes | Microcephaly |
| 17 | Support | A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders | Suzuki T et al. (2020) | Yes | - |
| 18 | Support | - | Tuncay IO et al. (2022) | Yes | - |
| 19 | Support | - | Woodbury-Smith M et al. (2022) | Yes | - |
| 20 | Support | - | Kim IB et al. (2022) | Yes | - |
| 21 | Support | - | N.Y.) (07/2) | Yes | - |
| 22 | Support | - | Zhou X et al. (2022) | Yes | - |
| 23 | Support | - | Cirnigliaro M et al. (2023) | Yes | - |
| 24 | Support | - | Yasser Al-Sarraj et al. (2024) | Yes | - |
Rare Variants (44)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.7926C>T | p.Ala2642%3D | synonymous_variant | De novo | - | - | 35901164 | N.Y.) (07/2) | |
| c.23282G>A | p.Trp7761Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.19479+3G>A | - | intron_variant | Familial | - | Simplex | 26539891 | Karaca E , et al. (2015) | |
| c.16024-3dup | - | splice_site_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
| c.23093A>G | p.Gln7698Arg | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1437T>C | p.Pro479%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2685G>A | p.Thr895%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.10041C>T | p.Val3347%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.6670G>A | p.Val2224Ile | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
| c.22520G>A | p.Arg7507His | missense_variant | De novo | - | Simplex | 31674007 | Wu H , et al. (2019) | |
| c.9080G>C | p.Cys3027Ser | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.546G>A | p.Lys182%3D | synonymous_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.11414G>A | p.Arg3805Gln | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
| c.10774C>G | p.Gln3592Glu | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.1437T>C | p.Pro479%3D | synonymous_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.6367T>C | p.Trp2123Arg | missense_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
| c.8236G>A | p.Glu2746Lys | missense_variant | Unknown | - | Simplex | 32530565 | Suzuki T et al. (2020) | |
| c.2330C>T | p.Ala777Val | missense_variant | De novo | - | Simplex | 28867142 | Krupp DR , et al. (2017) | |
| c.845A>G | p.Tyr282Cys | missense_variant | De novo | - | Simplex | 21572417 | O'Roak BJ , et al. (2011) | |
| c.11476A>G | p.Lys3826Glu | missense_variant | De novo | - | Simplex | 25961944 | Krumm N , et al. (2015) | |
| c.15170C>T | p.Ala5057Val | missense_variant | De novo | - | Simplex | 25961944 | Krumm N , et al. (2015) | |
| c.26029G>A | p.Glu8677Lys | missense_variant | Unknown | - | Simplex | 32530565 | Suzuki T et al. (2020) | |
| c.3229C>T | p.Pro1077Ser | missense_variant | De novo | - | Simplex | 23849776 | Jiang YH , et al. (2013) | |
| c.11668G>A | p.Val3890Ile | missense_variant | Unknown | - | - | 35205252 | Woodbury-Smith M et al. (2022) | |
| c.18052A>G | p.Asn6018Asp | missense_variant | Unknown | - | - | 35205252 | Woodbury-Smith M et al. (2022) | |
| c.18549G>A | p.Leu6183%3D | synonymous_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
| c.10748G>A | p.Arg3583Gln | missense_variant | Familial | - | Simplex | 26539891 | Karaca E , et al. (2015) | |
| c.3951G>A | p.Leu1317%3D | synonymous_variant | Unknown | - | - | 35205252 | Woodbury-Smith M et al. (2022) | |
| c.9604C>T | p.Arg3202Cys | missense_variant | Familial | Maternal | Simplex | 35840799 | Kim IB et al. (2022) | |
| c.91C>T | p.Arg31Ter | stop_gained | Familial | Maternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
| c.11072T>C | p.Leu3691Pro | missense_variant | Familial | Paternal | Simplex | 35840799 | Kim IB et al. (2022) | |
| c.4162C>T | p.Arg1388Trp | missense_variant | Familial | Maternal | Simplex | 35190550 | Tuncay IO et al. (2022) | |
| c.6031C>T | p.Arg2011Cys | missense_variant | Familial | Paternal | Simplex | 35190550 | Tuncay IO et al. (2022) | |
| c.16177-2A>G | - | splice_site_variant | Familial | Both parents | Unknown | 17159980 | Gros-Louis F , et al. (2006) | |
| c.9616C>A | p.Leu3206Met | missense_variant | Familial | Both parents | Multiplex | 23352163 | Yu TW , et al. (2013) | |
| c.8716A>T | p.Arg2096Ter | stop_gained | Familial | Both parents | Unknown | 17159980 | Gros-Louis F , et al. (2006) | |
| c.15705-12A>G | - | splice_site_variant | Familial | Both parents | Unknown | 17159980 | Gros-Louis F , et al. (2006) | |
| c.22918C>T | p.Gln7640Ter | stop_gained | Familial | Both parents | Unknown | 17159980 | Gros-Louis F , et al. (2006) | |
| c.939G>C | p.Lys313Asn | missense_variant | Familial | Both parents | Multiplex | 27457812 | Riazuddin S , et al. (2016) | |
| c.682C>T | p.Arg228Ter | stop_gained | Familial | Maternal | Extended multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
| c.7076C>A | p.Thr2359Asn | missense_variant | Familial | Both parents | Unknown | 38572415 | Yasser Al-Sarraj et al. (2024) | |
| 3343338-3343342delATTTG | - | frameshift_variant | Familial | Both parents | Unknown | 17159980 | Gros-Louis F , et al. (2006) | |
| c.24313-2A>G | p.His8105ValfsTer8 | splice_site_variant | Familial | Both parents | Extended multiplex | 19542096 | Attali R , et al. (2009) | |
| c.2548C>T | p.Leu850Phe | missense_variant | Familial | - | Extended multiplex (at least one pair of ASD affec | 24410847 | Cukier HN , et al. (2014) |
Common Variants (2)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.1653+2159C>A;c.1632+2159C>A;c.1602+2159C>A;c.1581+2159C>A;c.1512+2159C>A | T/G | intron_variant | - | - | - | 22565781 | Green EK , et al. (2012) | |
| c.3048+688C>T;c.3027+688C>T;c.2997+688C>T;c.2976+688C>T;c.2907+688C>T;c.2889+688C>T | A/G | intron_variant | - | - | - | 23453885 | Cross-Disorder Group of the Psychiatric Genomics Consortium (2013) |
SFARI Gene score
2
Strong Candidate
Rare mutations in the SYNE1 gene have been identified with autism (PMID 21572417) as well as with cerebellar ataxia and myogenic arthrogryposis multiplex congenita.
Score Delta: Score remained at 2
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.
4/1/2022
3S
2S
Decreased from 3S to 2S
Description
Rare mutations in the SYNE1 gene have been identified with autism (PMID 21572417) as well as with cerebellar ataxia and myogenic arthrogryposis multiplex congenita.
7/1/2020
3S
3S
Decreased from 3S to 3S
Description
Rare mutations in the SYNE1 gene have been identified with autism (PMID 21572417) as well as with cerebellar ataxia and myogenic arthrogryposis multiplex congenita.
10/1/2019
4S
3S
Decreased from 4S to 3S
New Scoring Scheme
Description
Rare mutations in the SYNE1 gene have been identified with autism (PMID 21572417) as well as with cerebellar ataxia and myogenic arthrogryposis multiplex congenita.
10/1/2017
4S
4S
Decreased from 4S to 4S
Description
Rare mutations in the SYNE1 gene have been identified with autism (PMID 21572417) as well as with cerebellar ataxia and myogenic arthrogryposis multiplex congenita.
7/1/2016
4S
4S
Decreased from 4S to 4S
Description
Rare mutations in the SYNE1 gene have been identified with autism (PMID 21572417) as well as with cerebellar ataxia and myogenic arthrogryposis multiplex congenita.
1/1/2016
4S
4S
Decreased from 4S to 4S
Description
Rare mutations in the SYNE1 gene have been identified with autism (PMID 21572417) as well as with cerebellar ataxia and myogenic arthrogryposis multiplex congenita.
Reports Added
[Mutation of SYNE-1, encoding an essential component of the nuclear lamina, is responsible for autosomal recessive arthrogryposis.2009] [Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia.2006] [Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.2011] [Using whole-exome sequencing to identify inherited causes of autism.2013] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders.2014] [Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.2013] [Association at SYNE1 in both bipolar disorder and recurrent major depression.2012] [Syne-1, a dystrophin- and Klarsicht-related protein associated with synaptic nuclei at the neuromuscular junction.2000] [SUN1/2 and Syne/Nesprin-1/2 complexes connect centrosome to the nucleus during neurogenesis and neuronal migration in mice.2009] [Excess of rare, inherited truncating mutations in autism.2015] [Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.2015] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014]4/1/2015
4S
4S
Decreased from 4S to 4S
Description
Rare mutations in the SYNE1 gene have been identified with autism (PMID 21572417) as well as with cerebellar ataxia and myogenic arthrogryposis multiplex congenita.
7/1/2014
No data
4S
Increased from No data to 4S
Description
Rare mutations in the SYNE1 gene have been identified with autism (PMID 21572417) as well as with cerebellar ataxia and myogenic arthrogryposis multiplex congenita.
4/1/2014
No data
4S
Increased from No data to 4S
Description
Rare mutations in the SYNE1 gene have been identified with autism (PMID 21572417) as well as with cerebellar ataxia and myogenic arthrogryposis multiplex congenita.
Krishnan Probability Score
Score 0.57114739143528
Ranking 818/25841 scored genes
[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning
approach on a human brain-specific gene network. The method was first presented in Nat
Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed
in column G of supplementary table 3 (see:
http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser,
with the ability to view networks of associated ASD risk genes, can be found at
asd.princeton.edu.
ExAC Score
Score 3.7506813929906E-27
Ranking 18124/18225 scored genes
[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has
been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by
Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at
exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of-
function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of-
function mutations in autism in such a gene would be more likely to confer risk. For a full list of
pLI scores see:
ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle
aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score
Score 0.95078609464839
Ranking 18628/18665 scored genes
[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013),
and is a statistic that integrates evidence from both de novo and transmitted mutations.
It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233
(2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper
(the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Larsen Cumulative Evidence Score
Score 18
Ranking 117/461 scored genes
[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available
ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size,
and variant frequency in the general population. The approach was first presented in Mol Autism
7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from
that paper.
Zhang D Score
Score 0.53291319441683
Ranking 323/20870 scored genes
[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures),
or D score, was developed to combine evidence from de novo loss-of- function mutation with
evidence from cell-type- specific gene expression in the mouse brain (specifically translational
profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with
positive D scores are more likely to be associated with autism risk, with higher-confidence genes
having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204-
215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in
supplementary table 2 from that paper.
External PIN Data
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 |
|---|---|---|---|---|---|
| emerin | Emerin | Human | Direct Regulation | 2010 | P50402 |
| Sh3glb2 | SH3 domain-containing GRB2-like endophilin B2 | Rat | Protein Binding | 311848 | Q5PPJ9 |
| SUN3 | Sad1 and UNC84 domain containing 3 | Human | Protein Binding | 256979 | Q8TAQ9 |
| SYNE3 | spectrin repeat containing, nuclear envelope family member 3 | Human | Protein Binding | 161176 | Q6ZMZ3 |
| US3 | N/A | HHV-1 | Protein Binding | 2703401 | B9VQJ7 |