SEMA4B

Chr 15

semaphorin 4B

Also known as: SEMAC, SemC

NCBI Gene: 10509 ENSG00000185033 UniProt: Q9NPR2 OMIM: 617029

The protein inhibits axonal extension by providing local signals that specify territories inaccessible for growing axons, functioning as a guidance cue during neural development. Mutations cause autosomal recessive retinal dystrophy with early childhood onset, primarily affecting vision and retinal function. The gene shows relatively low constraint against loss-of-function variants (pLI = 0.0005, LOEUF = 0.533), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable chemorepellent activity; neuropilin binding activity; and semaphorin receptor binding activity. Predicted to be involved in several processes, including axon guidance; neural crest cell migration; and semaphorin-plexin signaling pathway. Predicted to be located in membrane and synapse. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.53

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.53LOEUF

pLI 0.001

Z-score 3.83

OE 0.34 (0.22–0.53)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.96Z-score

OE missense 0.88 (0.81–0.95)

430 obs / 489.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.22–0.53)

0≤0.351.4

Missense OE?0.88 (0.81–0.95)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 13 / 38.8Missense obs/exp: 430 / 489.5Syn Z: -1.28

Background carrier burden — how many people carry a rare variant somewhere in SEMA4B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 33

1,241 rare PASS variants

Rare truncating (LoF)

1 in 750

181 rare PASS variants

Rare synonymous (reference)

1 in 89

485 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SEMA4B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 39	1 in 940
South Asian	~43k	1 in 41	1 in 530
Remaining (unassigned)	~30k	1 in 28	1 in 710
European (Finnish)	~27k	1 in 170	1 in 590
Admixed American	~22k	1 in 39	1 in 690
African / African American	~21k	1 in 36	1 in 710
East Asian	~20k	1 in 42	1 in 610
Ashkenazi Jewish	~13k	1 in 91	1 in 540
Middle Eastern	~2,884	1 in 29	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 13 of 14 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 14.? see exons ↓