SEMA7A

Chr 15AR

semaphorin 7A (JohnMiltonHagen blood group)

Also known as: CD108, CDw108, H-SEMA-K1, H-Sema-L, JMH, PFIC11, SEMAK1, SEMAL

NCBI Gene: 8482 ENSG00000138623 UniProt: O75326 OMIM: 607961

This gene encodes a member of the semaphorin family of proteins. The encoded preproprotein is proteolytically processed to generate the mature glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein. The encoded protein is found on activated lymphocytes and erythrocytes and may be involved in immunomodulatory and neuronal processes. The encoded protein carries the John Milton Hagen (JMH) blood group antigens. Mutations in this gene may be associated with reduced bone mineral density (BMD). Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Cholestasis, progressive familial intrahepatic, 11MIM #619874

[Blood group, John-Milton-Hagen system]MIM #614745

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

0.44

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.180

Z-score 4.01

OE 0.24 (0.14–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.84Z-score

OE missense 0.74 (0.67–0.82)

296 obs / 399.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.14–0.44)

0≤0.351.4

Missense OE?0.74 (0.67–0.82)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 8 / 32.8Missense obs/exp: 296 / 399.4Syn Z: -0.69

Background carrier burden — how many people carry a rare variant somewhere in SEMA7A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

815 rare PASS variants

Rare truncating (LoF)

1 in 4,900

70 rare PASS variants

Rare synonymous (reference)

1 in 74

393 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SEMA7A. 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 88	1 in 5,700
South Asian	~43k	1 in 49	1 in 4,600
Remaining (unassigned)	~30k	1 in 54	1 in 980
European (Finnish)	~27k	1 in 270	≈ 1 in 8,900
Admixed American	~22k	1 in 73	1 in 2,400
African / African American	~21k	1 in 57	≈ 1 in 4,400
East Asian	~20k	1 in 95	1 in 2,600
Ashkenazi Jewish	~13k	1 in 160	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 62	≈ 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 ↓