Human Gene Module / Chromosome 6 / SYNE1

SYNE1spectrin repeat containing, nuclear envelope 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
16 / 23
Rare Variants / Common Variants
43 / 2
Aliases
SYNE1, 8B,  CPG2,  ARCA1,  EDMD4,  MYNE1,  SCAR8
Associated Syndromes
-
Chromosome Band
6q25.2
Associated 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.

SFARI Genomic Platforms
Reports related to SYNE1 (23 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 -
Rare Variants   (43)
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)
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

2

Strong Candidate

See all Category 2 Genes

We 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
icon
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
icon
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
icon
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
icon
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
icon
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
icon
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.

4/1/2015
4S
icon
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
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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
icon
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.
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
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