Human Gene Module / Chromosome 6 / SYNE1

SYNE1spectrin repeat containing, nuclear envelope 1

Score
4S
Minimal Evidence, Syndromic Criteria 4.1, Syndromic
Autism Reports / Total Reports
8 / 15
Rare Variants / Common Variants
17 / 2
Aliases
SYNE1, 8B,  CPG2,  ARCA1,  EDMD4,  MYNE1,  SCAR8
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
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.

Reports related to SYNE1 (15 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 -
Rare Variants   (17)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
insA - splice_site_variant De novo - - 25363760 De Rubeis S , et al. (2014)
A310067G - splice_site_variant Familial - - 17159980 Gros-Louis F , et al. (2006)
c.22918C>T p.Gln7640Ter stop_gained Familial - - 17159980 Gros-Louis F , et al. (2006)
c.6670G>A p.Val2224Ile missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.11414G>A p.Arg3805Gln missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
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.3229C>T p.Pro1077Ser missense_variant De novo - Simplex 23849776 Jiang YH , et al. (2013)
A to G - splice_site_variant Familial Both parents Multi-generational 19542096 Attali R , et al. (2009)
c.[10748G>A];[19479+3G>A] p.[Arg3583Gln];[?] missense_variant;intron_variant Familial - Simplex 26539891 Karaca E , et al. (2015)
c.[9616C>A];[9616C>A] p.[Leu3206Met];[Leu3206Met] missense_variant Familial Both parents Multiplex 23352163 Yu TW , et al. (2013)
3343338-3343342delATTTG - frameshift_variant;frameshift_variant Familial Both parents Multiplex 17159980 Gros-Louis F , et al. (2006)
c.2548C>T p.Arg850Cys missense_variant Familial - Extended multiplex (at least one pair of ASD affec 24410847 Cukier HN , et al. (2014)
c.[939G>C];[939G>C] p.[Lys313Asn];[Lys313Asn] missense_variant;missense_variant Familial Both parents Multiplex 27457812 Riazuddin S , et al. (2016)
c.15705-12A>G;c.15918-12A>G;c.15939-12A>G - splice_site_variant;splice_site_variant Familial Both parents Multiplex 17159980 Gros-Louis F , et al. (2006)
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
4S

Minimal Evidence, Syndromic

4S

Score Delta: Score remained at 4.4 + S

4

Minimal Evidence

See all Category 4 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as 'acc" in the score cards) could also boost a gene from category 4 to 3.

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."

10/1/2017
4S
icon
4S

Score remained at 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

Score remained at 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

Score remained at 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

Score remained at 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
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.

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.
CNVs associated with SYNE1(1 CNVs)
6q25.2 5 Deletion-Duplication 9  /  12
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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