SEMA3A

Chr 7AD

semaphorin 3A

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

NCBI Gene: 10371 ENSG00000075213 UniProt: Q14563 OMIM: 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]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.311 OMIM phenotype

Clinical Summary— SEMA3A

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 190 VUS of 388 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SEMA3A

Authoritative clinical overview · Recommended first read

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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

388 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic4

VUS190

Likely Benign109

Benign61

Conflicting5

Pathogenic

Likely Pathogenic

190

VUS

109

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	2	0	3
Likely Pathogenic	4	0	0	0	4
VUS	5	175	9	1	190
Likely Benign	1	10	40	58	109
Benign	0	0	55	6	61
Conflicting	—				5
Total	11	185	106	65	372

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

18 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap SEMA3A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →