SEMA4G

protein-coding

semaphorin 4G, the group of Immunoglobulin like domain containing|Semaphorins|MicroRNA protein coding host genes

Gene summary

Semaphorins are a large family of conserved secreted and membrane associated proteins which possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Based on sequence and structural similarities, semaphorins are put into eight classes: invertebrates contain classes 1 and 2, viruses have class V, and vertebrates contain classes 3-7. Semaphorins serve as axon guidance ligands via multimeric receptor complexes, some (if not all) containing plexin proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

MANE transcript

NM_017893.4

Inheritance

—

ClinVar variants

U:132B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr10:100,969,504-100,985,871

External References & Databases

Ensembl (ENSG00000095539)

Transcript & Mutation Effects

hg38 • Region Span ~16.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SEMA4G variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 128

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017893.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	3 clinvar	4
missense			130 clinvar	2 clinvar	1 clinvar	133
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	132	3	4	139

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017893.4	RefSeq	NP_060363.2	14	MANE Select
ENST00000210633.4	Ensembl	ENSP00000210633.3	14	MANE Select
NM_001203244.1	RefSeq	NP_001190173.1	14	Standard
NM_001393925.1	RefSeq	NP_001380854.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Axon guidance - Homo sapiens (human)

Biological Process

neural crest cell migration
positive regulation of cell migration
negative regulation of axon extension involved in axon guidance
negative chemotaxis
semaphorin-plexin signaling pathway

Molecular Function

protein binding
semaphorin receptor binding
neuropilin binding
chemorepellent activity

Cellular Component

extracellular space
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000210633
Coding exons: 14
Length: 16354
Individuals with no LoFs: 125675
Homozygous LoFs: 0
Heterozygous LoFs: 73
Defined: 125748
p: 0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.953	456	517	0.882	0.0000330	5338
Missense (PolyPhen)		182	221.68	0.821		2295
Synonymous	1.11	181	201	0.901	0.0000109	1850
Loss of Function	2.73	19	36.9	0.515	0.00000208	403

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00054	0.00054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00044	0.00044	rare
South Asian	0.00016	0.00016	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cell surface receptor for PLXNB2. May play a role in axon guidance (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.758
RVIS EVS: -1.13
RVIS percentile EVS: 6.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.859

Gene Damage Prediction

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