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

ENSG00000187764 ∙ NCBI:10507 ∙ OMIM:601866 ∙ HGNC:10732 ∙ Uniprot:Q92854 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

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				9	7	16
missense			53	5	9	67
nonsense			2			2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3		3
non coding				1	3	4
Total	0	0	55	15	19

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 disorder	Benign (Oct 18, 2019)
9-89363849-G-A			Likely benign (Jun 21, 2018)
9-89363868-G-A		SEMA4D-related disorder	Benign (Oct 18, 2019)
9-89376938-C-A		SEMA4D-related disorder	Benign (Oct 28, 2019)
9-89376952-G-A		SEMA4D-related disorder	Likely benign (Jan 31, 2023)
9-89378700-G-A		SEMA4D-related disorder	Benign (Nov 26, 2019)
9-89378760-G-C		not specified	Uncertain significance (Aug 21, 2023)
9-89378781-C-T		not specified	Uncertain significance (Apr 28, 2022)
9-89378809-C-T		SEMA4D-related disorder	Benign (Feb 23, 2019)
9-89378841-C-T		not specified	Uncertain significance (Oct 03, 2022)
9-89378893-G-A		SEMA4D-related disorder	Likely benign (Jun 27, 2019)
9-89378898-A-G		not specified	Uncertain significance (Apr 26, 2023)
9-89378915-A-G		not specified	Uncertain significance (Oct 06, 2022)
9-89378917-C-T		SEMA4D-related disorder	Likely benign (Apr 01, 2024)
9-89378918-G-A		not specified	Uncertain significance (Jun 27, 2022)
9-89378931-T-C		not specified	Uncertain significance (Sep 16, 2021)
9-89378939-C-T		not specified	Uncertain significance (Oct 25, 2022)
9-89378940-G-A		not specified	Likely benign (May 10, 2022)
9-89379088-G-A		SEMA4D-related disorder	Likely benign (Mar 14, 2019)
9-89379092-C-T		not specified	Uncertain significance (Apr 27, 2022)
9-89379111-G-A		SEMA4D-related disorder	Benign (Jan 29, 2020)
9-89379146-G-A		not specified	Uncertain significance (Mar 18, 2024)
9-89379186-G-A		SEMA4D-related disorder	Benign (Feb 22, 2019)
9-89379234-C-A		not specified	Uncertain significance (Jan 23, 2024)
9-89379234-C-T		not specified	Uncertain significance (Jun 11, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SEMA4D	protein_coding	protein_coding	ENST00000450295	14	137344

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.975	0.0253	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.997	460	524	0.877	0.0000324	5644
Missense in Polyphen		88	158.38	0.55561		1720
Synonymous	0.451	222	231	0.962	0.0000165	1710
Loss of Function	4.79	6	37.8	0.159	0.00000186	447

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000121	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.000489	0.000272
Finnish	0.0000469	0.0000462
European (Non-Finnish)	0.0000180	0.0000176
Middle Eastern	0.000489	0.000272
South Asian	0.0000653	0.0000653
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

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