SEMA5Asema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 5A
Autism Reports / Total Reports
15 / 21Rare Variants / Common Variants
14 / 2Aliases
SEMA5A, Semaphorin 5A, semF, SEMAFAssociated Syndromes
-Chromosome Band
5p15.31Associated Disorders
IDRelevance to Autism
Expression of the SEMA5A gene has been shown to be down-regulated in some autistic individuals (Melin et al., 2006).
Molecular Function
The encoded protein is a member of the semaphorin family of membrane proteins that play roles in axonal guidance during neural development.
External Links
SFARI Genomic Platforms
Reports related to SEMA5A (21 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Recent Recommendation | Plexin-B3 is a functional receptor for semaphorin 5A | Artigiani S , et al. (2004) | No | - |
2 | Recent Recommendation | Semaphorin 5A is a bifunctional axon guidance cue regulated by heparan and chondroitin sulfate proteoglycans | Kantor DB , et al. (2004) | No | - |
3 | Highly Cited | Inactivation of the Sema5a gene results in embryonic lethality and defective remodeling of the cranial vascular system | Fiore R , et al. (2005) | No | - |
4 | Primary | Constitutional downregulation of SEMA5A expression in autism | Melin M , et al. (2006) | Yes | - |
5 | Positive Association | A genome-wide linkage and association scan reveals novel loci for autism | Weiss LA , et al. (2009) | Yes | - |
6 | Negative Association | The association of rs4307059 and rs35678 markers with autism spectrum disorders is replicated in Italian families | Prandini P , et al. (2012) | Yes | - |
7 | Support | Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder | Girirajan S , et al. (2013) | Yes | - |
8 | Recent Recommendation | An eQTL mapping approach reveals that rare variants in the SEMA5A regulatory network impact autism risk | Cheng Y , et al. (2013) | No | - |
9 | Recent Recommendation | The SEMA5A gene is associated with hippocampal volume, and their interaction is associated with performance on Raven's Progressive Matrices | Zhu B , et al. (2013) | No | - |
10 | Support | Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel | Brett M , et al. (2014) | Yes | MCA |
11 | Recent Recommendation | Semaphorin 5A inhibits synaptogenesis in early postnatal- and adult-born hippocampal dentate granule cells | Duan Y , et al. (2014) | No | - |
12 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
13 | Support | A de novo microdeletion of SEMA5A in a boy with autism spectrum disorder and intellectual disability | Mosca-Boidron AL , et al. (2015) | Yes | ID |
14 | Support | Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms | D'Gama AM , et al. (2015) | Yes | - |
15 | Negative Association | Lack of replication of previous autism spectrum disorder GWAS hits in European populations | Torrico B , et al. (2016) | Yes | - |
16 | Positive Association | Polymorphism in the Promoter Region of SEMA5A Is Associated with Sociality Traits in Korean Subjects with Autism Spectrum Disorders | Kim SA , et al. (2017) | Yes | Sociability traits (as measured by SRS) |
17 | Support | Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks | Ruzzo EK , et al. (2019) | Yes | - |
18 | Support | - | Zhou X et al. (2022) | Yes | - |
19 | Support | - | Hu C et al. (2023) | Yes | - |
20 | Support | - | Miyu Okabe et al. (2023) | Yes | - |
21 | Support | - | Morgane E Le Dréan et al. (2024) | Yes | - |
Rare Variants (14)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | copy_number_loss | De novo | - | Simplex | 23375656 | Girirajan S , et al. (2013) | |
- | - | copy_number_loss | De novo | - | Simplex | 26395558 | Mosca-Boidron AL , et al. (2015) | |
c.1361G>C | p.Arg454Thr | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.2872G>A | p.Val958Ile | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.3106-5dup | - | splice_region_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
c.586C>T | p.Arg196Ter | stop_gained | Unknown | - | Unknown | 26637798 | D'Gama AM , et al. (2015) | |
c.2026C>T | p.Arg676Cys | missense_variant | Familial | Paternal | - | 37007974 | Hu C et al. (2023) | |
c.2103T>A | p.Cys701Ter | stop_gained | De novo | - | Multiplex | 31398340 | Ruzzo EK , et al. (2019) | |
c.246G>T | p.Gln82His | missense_variant | Unknown | Not tested | - | 24690944 | Brett M , et al. (2014) | |
c.2271C>T | p.Ser757%3D | synonymous_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
c.2852C>G | p.Ser951Cys | missense_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
c.2866A>G | p.Ser956Gly | missense_variant | Unknown | - | Unknown | 26395558 | Mosca-Boidron AL , et al. (2015) | |
c.2026C>T | p.Arg676Cys | missense_variant | Familial | Maternal | Simplex | 26395558 | Mosca-Boidron AL , et al. (2015) | |
c.2983C>T | p.Arg995Trp | missense_variant | Familial | Maternal | Simplex | 26395558 | Mosca-Boidron AL , et al. (2015) |
Common Variants (2)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | intergenic_variant | - | - | - | 29209394 | Kim SA , et al. (2017) | |
- | - | intergenic_variant | - | - | - | 19812673 | Weiss LA , et al. (2009) |
SFARI Gene score
Strong Candidate
A common variant located in the EST DB512398, located between SEMA5A and TAS2R1, was found to be associated with autism (P = 1.7 x 10-7 considering discovery and replication cohorts). The weak block structure in the region doesn?t seem to permit simple assignment of rs10513025 to SEMA5A (perhaps neighboring SNPs are better in this regard). Neither EST nor SNORD123, each closer to the SNP in question than SEMA5A, were really discussed as possible candidates. Significantly different expression levels for SEMA5A were observed in occipital cortex of ASD cases and controls (Melin M et al.).
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.
10/1/2019
Decreased from 3 to 2
New Scoring Scheme
Description
A common variant located in the EST DB512398, located between SEMA5A and TAS2R1, was found to be associated with autism (P = 1.7 x 10-7 considering discovery and replication cohorts). The weak block structure in the region doesn?t seem to permit simple assignment of rs10513025 to SEMA5A (perhaps neighboring SNPs are better in this regard). Neither EST nor SNORD123, each closer to the SNP in question than SEMA5A, were really discussed as possible candidates. Significantly different expression levels for SEMA5A were observed in occipital cortex of ASD cases and controls (Melin M et al.).
Reports Added
[New Scoring Scheme]7/1/2019
Decreased from 3 to 3
Description
A common variant located in the EST DB512398, located between SEMA5A and TAS2R1, was found to be associated with autism (P = 1.7 x 10-7 considering discovery and replication cohorts). The weak block structure in the region doesn?t seem to permit simple assignment of rs10513025 to SEMA5A (perhaps neighboring SNPs are better in this regard). Neither EST nor SNORD123, each closer to the SNP in question than SEMA5A, were really discussed as possible candidates. Significantly different expression levels for SEMA5A were observed in occipital cortex of ASD cases and controls (Melin M et al.).
7/1/2016
Decreased from 3 to 3
Description
A common variant located in the EST DB512398, located between SEMA5A and TAS2R1, was found to be associated with autism (P = 1.7 x 10-7 considering discovery and replication cohorts). The weak block structure in the region doesn?t seem to permit simple assignment of rs10513025 to SEMA5A (perhaps neighboring SNPs are better in this regard). Neither EST nor SNORD123, each closer to the SNP in question than SEMA5A, were really discussed as possible candidates. Significantly different expression levels for SEMA5A were observed in occipital cortex of ASD cases and controls (Melin M et al.).
1/1/2016
Decreased from 3 to 3
Description
A common variant located in the EST DB512398, located between SEMA5A and TAS2R1, was found to be associated with autism (P = 1.7 x 10-7 considering discovery and replication cohorts). The weak block structure in the region doesn?t seem to permit simple assignment of rs10513025 to SEMA5A (perhaps neighboring SNPs are better in this regard). Neither EST nor SNORD123, each closer to the SNP in question than SEMA5A, were really discussed as possible candidates. Significantly different expression levels for SEMA5A were observed in occipital cortex of ASD cases and controls (Melin M et al.).
Reports Added
[Constitutional downregulation of SEMA5A expression in autism.2006] [A genome-wide linkage and association scan reveals novel loci for autism.2009] [The association of rs4307059 and rs35678 markers with autism spectrum disorders is replicated in Italian families.2012] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene ...2014] [Plexin-B3 is a functional receptor for semaphorin 5A.2004] [Semaphorin 5A is a bifunctional axon guidance cue regulated by heparan and chondroitin sulfate proteoglycans.2004] [Inactivation of the Sema5a gene results in embryonic lethality and defective remodeling of the cranial vascular system.2005] [An eQTL mapping approach reveals that rare variants in the SEMA5A regulatory network impact autism risk.2013] [The SEMA5A gene is associated with hippocampal volume, and their interaction is associated with performance on Raven's Progressive Matrices.2013] [Semaphorin 5A inhibits synaptogenesis in early postnatal- and adult-born hippocampal dentate granule cells.2014] [A de novo microdeletion of SEMA5A in a boy with autism spectrum disorder and intellectual disability.2015] [Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014]10/1/2014
Decreased from 3 to 3
Description
A common variant located in the EST DB512398, located between SEMA5A and TAS2R1, was found to be associated with autism (P = 1.7 x 10-7 considering discovery and replication cohorts). The weak block structure in the region doesn?t seem to permit simple assignment of rs10513025 to SEMA5A (perhaps neighboring SNPs are better in this regard). Neither EST nor SNORD123, each closer to the SNP in question than SEMA5A, were really discussed as possible candidates. Significantly different expression levels for SEMA5A were observed in occipital cortex of ASD cases and controls (Melin M et al.).
7/1/2014
Increased from No data to 3
Description
A common variant located in the EST DB512398, located between SEMA5A and TAS2R1, was found to be associated with autism (P = 1.7 x 10-7 considering discovery and replication cohorts). The weak block structure in the region doesn?t seem to permit simple assignment of rs10513025 to SEMA5A (perhaps neighboring SNPs are better in this regard). Neither EST nor SNORD123, each closer to the SNP in question than SEMA5A, were really discussed as possible candidates. Significantly different expression levels for SEMA5A were observed in occipital cortex of ASD cases and controls (Melin M et al.).
4/1/2014
Increased from No data to 3
Description
A common variant located in the EST DB512398, located between SEMA5A and TAS2R1, was found to be associated with autism (P = 1.7 x 10-7 considering discovery and replication cohorts). The weak block structure in the region doesn?t seem to permit simple assignment of rs10513025 to SEMA5A (perhaps neighboring SNPs are better in this regard). Neither EST nor SNORD123, each closer to the SNP in question than SEMA5A, were really discussed as possible candidates. Significantly different expression levels for SEMA5A were observed in occipital cortex of ASD cases and controls (Melin M et al.).
Krishnan Probability Score
Score 0.53056394384165
Ranking 1546/25841 scored genes
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ExAC Score
Score 0.0009795943226773
Ranking 11799/18225 scored genes
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Sanders TADA Score
Score 0.94382568694961
Ranking 15837/18665 scored genes
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Larsen Cumulative Evidence Score
Score 12
Ranking 163/461 scored genes
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Zhang D Score
Score 0.33055474455293
Ranking 2287/20870 scored genes
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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 |
---|---|---|---|---|---|
PLXNB3 | plexin B3 | Human | Protein Binding | 5365 | Q9ULL4 |