SEMA3A

Chr 7AD

semaphorin 3A

Also known as: COLL1, HH16, Hsema-I, Hsema-III, SEMA1, SEMAD, SEMAIII, SEMAL

NCBI Gene: 10371ENSG00000075213UniProt: Q14563OMIM: 603961

This gene is a member of the semaphorin family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a Sema domain. This secreted protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. In both cases, the protein is vital for normal neuronal pattern development. Increased expression of this protein is associated with schizophrenia and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of Alzheimer's disease. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Hypogonadotropic hypogonadism 16 with or without anosmia}MIM #614897
AD

Clinical highlights

Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
121
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.31
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — SEMA3A
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.31LOEUF
pLI 0.978
Z-score 5.27
OE 0.17 (0.10–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.75Z-score
OE missense 0.76 (0.70–0.83)
327 obs / 429.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.17 (0.10–0.31)
0≤0.351.4
Missense OE?0.76 (0.70–0.83)
0≤0.61.4
Synonymous OE?0.95
0≤1.21.6
LoF obs/exp: 8 / 47.0Missense obs/exp: 327 / 429.0Syn Z: 0.51

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SEMA3A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients