MS4A15

Chr 11

membrane spanning 4-domains A15

NCBI Gene: 219995 ENSG00000166961 UniProt: Q8N5U1

The protein is predicted to function as a component of multimeric receptor complexes involved in cell surface signaling pathways at the plasma membrane. The gene shows low constraint against loss-of-function variants (pLI = 0.0004, LOEUF = 1.4), and no definitive disease associations have been established in pediatric neurogenetic disorders based on the available data.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in cell surface receptor signaling pathway. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.40

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?

1.40LOEUF

pLI 0.000

Z-score 0.77

OE 0.71 (0.39–1.40)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.23Z-score

OE missense 0.95 (0.82–1.09)

138 obs / 145.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.71 (0.39–1.40)

0≤0.351.4

Missense OE?0.95 (0.82–1.09)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 6 / 8.4Missense obs/exp: 138 / 145.9Syn Z: -0.65

Background carrier burden — how many people carry a rare variant somewhere in MS4A15?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

334 rare PASS variants

Rare truncating (LoF)

1 in 1,300

60 rare PASS variants

Rare synonymous (reference)

1 in 230

133 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MS4A15. 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 210	1 in 1,300
South Asian	~43k	1 in 140	1 in 640
Remaining (unassigned)	~30k	1 in 82	1 in 2,000
European (Finnish)	~27k	1 in 500	≈ 1 in 6,100
Admixed American	~22k	1 in 98	≈ 1 in 5,300
African / African American	~21k	1 in 130	1 in 1,400
East Asian	~20k	1 in 180	≈ 1 in 9,500
Ashkenazi Jewish	~13k	1 in 740	≈ 1 in 6,300
Middle Eastern	~2,884	1 in 170	≈ 1 in 2,500

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 ↓