SEMA6A

Chr 5

semaphorin 6A

Also known as: HT018, SEMA, SEMA6A1, SEMAQ, VIA

NCBI Gene: 57556 ENSG00000092421 UniProt: Q9H2E6

Predicted to enable identical protein binding activity; signaling receptor binding activity; and transmembrane signaling receptor activity. Involved in cellular response to vascular endothelial growth factor stimulus; negative regulation of cell adhesion involved in sprouting angiogenesis; and negative regulation of signal transduction. Predicted to be located in axon and membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

Research

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.22

Clinical Summary— SEMA6A

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 154 VUS of 192 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.22LOEUF

pLI 1.000

Z-score 5.39

OE 0.10 (0.05–0.22)

Highly constrained

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

Missense Constraint?

0.75Z-score

OE missense 0.91 (0.85–0.98)

543 obs / 594.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.05–0.22)

0≤0.351.4

Missense OE?0.91 (0.85–0.98)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 4 / 41.4Missense obs/exp: 543 / 594.2Syn Z: -1.23

This gene — mechanism propensity

0.4090th %ile

GOF

0.4480th %ile

LOF

0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.22

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

192 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic2

VUS154

Likely Benign3

Likely Pathogenic

154

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	1	1	0	2
VUS	3	151	0	154
Likely Benign	0	2	1	3
Benign	0	0	0	0
Total	4	154	1	159

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

View in ClinVar →

2 pathogenic / likely-pathogenic (of 8) ClinVar copy-number / structural variants overlap SEMA6A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →