MS4A12

Chr 11

membrane spanning 4-domains A12

Also known as: Ms4a10

NCBI Gene: 54860 ENSG00000071203 UniProt: Q9NXJ0

MS4A12 encodes a cell surface protein that localizes to the apical membrane of colonocytes and may function in signal transduction as part of a multimeric receptor complex. The gene shows extremely low constraint against loss-of-function variants (pLI near zero), and no established Mendelian diseases have been associated with MS4A12 mutations in pediatric populations.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a cell surface protein found primarily in the apical membrane of colonocytes. Silencing of this gene in colon cancer cells inhibits the proliferation, cell motility, and chemotactic invasion of cells. This gene is part of a cluster of similar genes found on chromosome 11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.79

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.79LOEUF

pLI 0.000

Z-score -0.50

OE 1.17 (0.74–1.79)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.12Z-score

OE missense 1.03 (0.90–1.18)

152 obs / 147.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.17 (0.74–1.79)

0≤0.351.4

Missense OE?1.03 (0.90–1.18)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 12 / 10.3Missense obs/exp: 152 / 147.9Syn Z: 0.72

Background carrier burden — how many people carry a rare variant somewhere in MS4A12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

370 rare PASS variants

Rare truncating (LoF)

1 in 1,900

63 rare PASS variants

Rare synonymous (reference)

1 in 510

115 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MS4A12. 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 260	1 in 1,100
South Asian	~43k	1 in 110	1 in 1,100
Remaining (unassigned)	~30k	1 in 83	1 in 1,500
European (Finnish)	~27k	1 in 420	≈ 1 in 13,000
Admixed American	~22k	1 in 130	1 in 300
African / African American	~21k	1 in 97	1 in 590
East Asian	~20k	1 in 110	1 in 520
Ashkenazi Jewish	~13k	≈ 1 in 6,500	1 in 2,200
Middle Eastern	~2,884	1 in 97	≈ 1 in 2,900

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): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓