Menu
GeneBe

SEMA4D

semaphorin 4D, the group of Immunoglobulin like domain containing|Semaphorins|CD molecules

Basic information

Region (hg38): 9:89360786-89498130

Previous symbols: [ "SEMAJ", "C9orf164" ]

Links

ENSG00000187764NCBI:10507OMIM:601866HGNC:10732Uniprot:Q92854AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEMA4D gene.

  • Inborn genetic diseases (33 variants)
  • not provided (8 variants)
  • Anti-SEMA4D Monoclonal Antibody VX15/2503 (1 variants)
  • See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEMA4D 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
3
clinvar
1
clinvar
4
missense
33
clinvar
3
clinvar
36
nonsense
2
clinvar
2
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
0
non coding
1
clinvar
1
Total 0 0 35 6 2

Variants in SEMA4D

This is a list of pathogenic ClinVar variants found in the SEMA4D region.

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

Position Type Phenotype Significance ClinVar
9-89363482-C-T SEMA4D-related condition Benign (Oct 18, 2019)3060820
9-89363849-G-A Likely benign (Jun 21, 2018)1317919
9-89363868-G-A SEMA4D-related condition Benign (Oct 18, 2019)3060340
9-89376938-C-A SEMA4D-related condition Benign (Oct 28, 2019)3049327
9-89376952-G-A SEMA4D-related condition Likely benign (Jan 31, 2023)3041927
9-89378700-G-A SEMA4D-related condition Benign (Nov 26, 2019)3039346
9-89378760-G-C not specified Uncertain significance (Aug 21, 2023)2620389
9-89378781-C-T not specified Uncertain significance (Apr 28, 2022)2286803
9-89378809-C-T SEMA4D-related condition Benign (Feb 23, 2019)3056145
9-89378841-C-T not specified Uncertain significance (Oct 03, 2022)2315790
9-89378893-G-A SEMA4D-related condition Likely benign (Jun 27, 2019)3042521
9-89378898-A-G not specified Uncertain significance (Apr 26, 2023)2541025
9-89378915-A-G not specified Uncertain significance (Oct 06, 2022)2317455
9-89378917-C-T SEMA4D-related condition Likely benign (Dec 31, 2019)710800
9-89378918-G-A not specified Uncertain significance (Jun 27, 2022)2382988
9-89378931-T-C not specified Uncertain significance (Sep 16, 2021)2305990
9-89378939-C-T not specified Uncertain significance (Oct 25, 2022)2319224
9-89378940-G-A not specified Likely benign (May 10, 2022)2204128
9-89379088-G-A SEMA4D-related condition Likely benign (Mar 14, 2019)3045892
9-89379092-C-T not specified Uncertain significance (Apr 27, 2022)2411287
9-89379111-G-A SEMA4D-related condition Benign (Jan 29, 2020)3044594
9-89379186-G-A SEMA4D-related condition Benign (Feb 22, 2019)3056239
9-89379234-C-A not specified Uncertain significance (Jan 23, 2024)3159812
9-89379234-C-T not specified Uncertain significance (Jun 11, 2021)2232320
9-89379242-G-A not specified Uncertain significance (Jun 18, 2021)2233373

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SEMA4Dprotein_codingprotein_codingENST00000450295 14137344
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9750.02531257350131257480.0000517
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.9974605240.8770.00003245644
Missense in Polyphen88158.380.555611720
Synonymous0.4512222310.9620.00001651710
Loss of Function4.79637.80.1590.00000186447

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001210.000119
Ashkenazi Jewish0.000.00
East Asian0.0004890.000272
Finnish0.00004690.0000462
European (Non-Finnish)0.00001800.0000176
Middle Eastern0.0004890.000272
South Asian0.00006530.0000653
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Cell surface receptor for PLXN1B and PLXNB2 that plays an important role in cell-cell signaling. Promotes reorganization of the actin cytoskeleton and plays a role in axonal growth cone guidance in the developing central nervous system. Regulates dendrite and axon branching and morphogenesis. Promotes the migration of cerebellar granule cells and of endothelial cells. Plays a role in the immune system; induces B-cells to aggregate and improves their viability (in vitro). Promotes signaling via SRC and PTK2B/PYK2, which then mediates activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Interaction with PLXNB1 mediates activation of RHOA. {ECO:0000269|PubMed:16055703, ECO:0000269|PubMed:19788569, ECO:0000269|PubMed:20877282, ECO:0000269|PubMed:8876214}.;
Pathway
Axon guidance - Homo sapiens (human);Developmental Biology;Sema4D mediated inhibition of cell attachment and migration;Sema4D induced cell migration and growth-cone collapse;Sema4D in semaphorin signaling;Other semaphorin interactions;Semaphorin interactions;Axon guidance (Consensus)

Recessive Scores

pRec
0.224

Intolerance Scores

loftool
0.787
rvis_EVS
0.12
rvis_percentile_EVS
62.24

Haploinsufficiency Scores

pHI
0.235
hipred
Y
hipred_score
0.595
ghis
0.477

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.725

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Sema4d
Phenotype
homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; immune system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);

Zebrafish Information Network

Gene name
sema4d
Affected structure
trunk
Phenotype tag
abnormal
Phenotype quality
curved

Gene ontology

Biological process
negative regulation of transcription by RNA polymerase II;neural crest cell migration;positive regulation of protein phosphorylation;immune response;cell adhesion;negative regulation of cell adhesion;regulation of cell shape;negative regulation of alkaline phosphatase activity;positive regulation of phosphatidylinositol 3-kinase signaling;positive regulation of cell migration;regulation of cell projection organization;negative regulation of apoptotic process;positive regulation of GTPase activity;ossification involved in bone maturation;negative regulation of osteoblast differentiation;positive regulation of collateral sprouting;regulation of dendrite morphogenesis;negative regulation of axon extension involved in axon guidance;positive regulation of peptidyl-tyrosine phosphorylation;negative regulation of peptidyl-tyrosine phosphorylation;negative chemotaxis;leukocyte aggregation;semaphorin-plexin signaling pathway;semaphorin-plexin signaling pathway involved in bone trabecula morphogenesis
Cellular component
extracellular space;plasma membrane;integral component of plasma membrane
Molecular function
transmembrane signaling receptor activity;signaling receptor binding;protein binding;semaphorin receptor binding;signaling receptor activity;neuropilin binding;chemorepellent activity