SEMA3F

protein-coding

semaphorin 3F, the group of Immunoglobulin like domain containing|Semaphorins|MicroRNA protein coding host genes

Gene summary

This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin loop and a C-terminal basic domain. This gene is expressed by the endothelial cells where it was found to act in an autocrine fashion to induce apoptosis, inhibit cell proliferation and survival, and function as an anti-tumorigenic agent. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

MANE transcript

NM_004186.5

Inheritance

ClinVar variants

U:282B:122

Top phenotype

hypogonadotropic hypogonadism

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr3:50,155,045-50,189,075

External References & Databases

Ensembl (ENSG00000001617)

Transcript & Mutation Effects

hg38 • Region Span ~34.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypogonadotropic hypogonadismSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0018555

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SEMA3F variants in ClinVar

5 Conditions Cataloged

SEMA3F-related disorderTotal: 363

not specifiedTotal: 108

not providedTotal: 10

Hypogonadotropic hypogonadismTotal: 8

Hearing impairmentTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004186.5. 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			9 clinvar	110 clinvar		119
missense			261 clinvar	11 clinvar	1 clinvar	273
nonsense			5 clinvar			5
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	282	121	1	404

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004186.5	RefSeq	NP_004177.3	18	MANE Select
ENST00000002829.8	Ensembl	ENSP00000002829.3	18	MANE Select
NM_001318798.2	RefSeq	NP_001305727.1	16	Standard
NM_001318800.2	RefSeq	NP_001305729.1	17	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
axon guidance
facial nerve structural organization
trigeminal nerve structural organization
nerve development

Molecular Function

semaphorin receptor binding
neuropilin binding
chemorepellent activity

Cellular Component

extracellular space
integral component of plasma membrane
glutamatergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000002829
Coding exons: 18
Length: 34031
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125739
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.47	388	551	0.704	0.0000389	5061
Missense (PolyPhen)		126	249.36	0.5053		2240
Synonymous	0.608	214	226	0.949	0.0000164	1621
Loss of Function	5.75	5	47.9	0.104	0.00000293	444

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000064	0.000062	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in cell motility and cell adhesion.;

Recessive Scores

pRec: 0.149

Intolerance Scores

LoFtool: 0.158
RVIS EVS: -0.26
RVIS percentile EVS: 34.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.124

Gene Damage Prediction

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