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GeneBe

SEMA4A

semaphorin 4A, the group of Semaphorins

Basic information

Region (hg38): 1:156147365-156177752

Previous symbols: [ "SEMAB" ]

Links

ENSG00000196189NCBI:64218OMIM:607292HGNC:10729Uniprot:Q9H3S1AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • retinitis pigmentosa (Supportive), mode of inheritance: AD
  • cone-rod dystrophy (Supportive), mode of inheritance: AD
  • familial colorectal cancer type X (Supportive), mode of inheritance: AD
  • retinitis pigmentosa 35 (Limited), mode of inheritance: AR
  • cone-rod dystrophy 10 (Limited), mode of inheritance: Unknown
  • retinitis pigmentosa 35 (Limited), mode of inheritance: Unknown
  • Lynch syndrome (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Cone-rod dystrophy 10; Retinitis pigmentosa 35ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingOphthalmologic16199541

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEMA4A gene.

  • not provided (468 variants)
  • Cone-rod dystrophy 10 (83 variants)
  • Retinitis pigmentosa (60 variants)
  • Retinitis pigmentosa 35 (41 variants)
  • Retinitis Pigmentosa, Recessive (36 variants)
  • Inborn genetic diseases (23 variants)
  • not specified (9 variants)
  • Retinal dystrophy (4 variants)
  • Cone-rod dystrophy 10;Retinitis pigmentosa 35 (3 variants)
  • Colorectal cancer (2 variants)
  • Cone-Rod Dystrophy, Recessive (2 variants)
  • Polyp of colon (1 variants)
  • Helicoid peripapillary chorioretinal degeneration (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEMA4A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
5
clinvar
87
clinvar
1
clinvar
93
missense
253
clinvar
6
clinvar
259
nonsense
1
clinvar
8
clinvar
9
start loss
1
clinvar
1
frameshift
1
clinvar
2
clinvar
9
clinvar
12
inframe indel
7
clinvar
7
splice donor/acceptor (+/-2bp)
6
clinvar
1
clinvar
7
splice region
4
15
19
non coding
19
clinvar
47
clinvar
6
clinvar
72
Total 2 2 308 140 8

Highest pathogenic variant AF is 0.0000131

Variants in SEMA4A

This is a list of pathogenic ClinVar variants found in the SEMA4A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
1-156153519-C-T Cone-Rod Dystrophy, Recessive • Retinitis Pigmentosa, Recessive Uncertain significance (Jun 14, 2016)368834
1-156153629-G-A Cone-rod dystrophy 10 • Retinitis Pigmentosa, Recessive • Retinitis pigmentosa Uncertain significance (Jan 13, 2018)292841
1-156153730-A-G Cone-rod dystrophy 10 • Retinitis Pigmentosa, Recessive • Retinitis pigmentosa Uncertain significance (Jan 13, 2018)292842
1-156154580-T-A Uncertain significance (Mar 20, 2022)2115352
1-156154589-C-T Uncertain significance (Jun 14, 2023)955649
1-156154592-C-G Uncertain significance (Dec 28, 2020)954000
1-156154598-G-A Retinitis pigmentosa • Cone-rod dystrophy 10 Conflicting classifications of pathogenicity (Jan 25, 2024)767708
1-156154612-A-T Uncertain significance (Apr 05, 2021)1523345
1-156154616-T-C not specified Uncertain significance (Oct 05, 2023)1370959
1-156154621-G-T Uncertain significance (Sep 23, 2022)1720220
1-156154623-C-T Likely benign (Nov 23, 2021)1140776
1-156154639-C-T Likely benign (Mar 26, 2022)2095696
1-156154654-C-A Uncertain significance (May 19, 2021)1487914
1-156154655-T-C Uncertain significance (Sep 27, 2022)857841
1-156154655-T-TGCC Uncertain significance (Aug 16, 2022)1394287
1-156154657-C-T Uncertain significance (Oct 14, 2022)1936583
1-156154657-CCGA-C Uncertain significance (Nov 10, 2023)1522316
1-156154658-C-T Uncertain significance (Nov 12, 2023)1051004
1-156154659-G-A SEMA4A-related condition Likely benign (Jan 21, 2020)3051241
1-156154661-C-T Uncertain significance (Aug 08, 2022)1441368
1-156154662-G-A not specified • Retinitis Pigmentosa, Recessive • Cone-rod dystrophy 10 • Retinitis pigmentosa Conflicting classifications of pathogenicity (Dec 13, 2023)195371
1-156154662-G-GA Uncertain significance (Feb 24, 2023)3005775
1-156154664-C-T Cone-rod dystrophy 10 • Retinitis pigmentosa 35 • not specified Uncertain significance (Apr 11, 2023)1000955
1-156154665-G-A Likely benign (Sep 27, 2022)1963123
1-156154667-C-A Uncertain significance (Mar 20, 2022)1958724

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SEMA4Aprotein_codingprotein_codingENST00000368285 1430387
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.00001841.001256830651257480.000258
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.2234124250.9700.00002454921
Missense in Polyphen111130.640.849671603
Synonymous0.3881731800.9630.00001021595
Loss of Function3.191434.10.4100.00000185373

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0005350.000535
Ashkenazi Jewish0.0002980.000198
East Asian0.0002720.000272
Finnish0.00004620.0000462
European (Non-Finnish)0.0002300.000229
Middle Eastern0.0002720.000272
South Asian0.0005250.000523
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Cell surface receptor for PLXNB1, PLXNB2, PLXNB3 and PLXND1 that plays an important role in cell-cell signaling. Plays a role in priming antigen-specific T-cells, promotes differentiation of Th1 T-helper cells, and thereby contributes to adaptive immunity. Promotes phosphorylation of TIMD2. Inhibits angiogenesis. Promotes axon growth cone collapse. Inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons (By similarity). {ECO:0000250|UniProtKB:Q62178}.;
Disease
DISEASE: Retinitis pigmentosa 35 (RP35) [MIM:610282]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:16199541, ECO:0000269|PubMed:22956603}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cone-rod dystrophy 10 (CORD10) [MIM:610283]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:16199541}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Axon guidance - Homo sapiens (human);Angiogenesis overview;Developmental Biology;Other semaphorin interactions;Semaphorin interactions;Plexin-D1 Signaling;Axon guidance (Consensus)

Recessive Scores

pRec
0.127

Intolerance Scores

loftool
0.895
rvis_EVS
0.02
rvis_percentile_EVS
55.76

Haploinsufficiency Scores

pHI
0.768
hipred
Y
hipred_score
0.655
ghis
0.519

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.739

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Sema4a
Phenotype
cellular phenotype; immune system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); pigmentation phenotype; hematopoietic system phenotype;

Zebrafish Information Network

Gene name
sema4aa
Affected structure
retinal outer plexiform layer
Phenotype tag
abnormal
Phenotype quality
morphology

Gene ontology

Biological process
angiogenesis;neural crest cell migration;axonogenesis;regulation of cell shape;regulation of endothelial cell migration;negative regulation of angiogenesis;positive regulation of cell migration;T-helper 1 cell differentiation;negative regulation of axon extension involved in axon guidance;negative chemotaxis;semaphorin-plexin signaling pathway
Cellular component
extracellular space;nucleus;cytosol;plasma membrane;integral component of plasma membrane;intracellular membrane-bounded organelle
Molecular function
protein binding;semaphorin receptor binding;neuropilin binding;chemorepellent activity