MS4A14

Chr 11

membrane spanning 4-domains A14

The protein is predicted to function in cell surface receptor signaling pathways as a component of multimeric receptor complexes at the plasma membrane. This gene shows low constraint against loss-of-function variants (LOEUF 1.76), and no definitive human disease associations have been established for MS4A14 mutations. The clinical significance of variants in this gene remains uncertain.

ResearchSummary from RefSeq, UniProt

May be involved in signal transduction as a component of a multimeric receptor complex

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.76

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.76LOEUF

pLI 0.000

Z-score -0.20

OE 1.07 (0.64–1.76)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.06Z-score

OE missense 1.01 (0.92–1.10)

354 obs / 350.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.07 (0.64–1.76)

0≤0.351.4

Missense OE?1.01 (0.92–1.10)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 9 / 8.4Missense obs/exp: 354 / 350.9Syn Z: -1.56

Background carrier burden — how many people carry a rare variant somewhere in MS4A14?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 69

924 rare PASS variants

Rare truncating (LoF)

1 in 440

152 rare PASS variants

Rare synonymous (reference)

1 in 96

359 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MS4A14. 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 110	1 in 600
South Asian	~43k	1 in 60	1 in 400
Remaining (unassigned)	~30k	1 in 51	1 in 440
European (Finnish)	~27k	1 in 590	1 in 3,000
Admixed American	~22k	1 in 61	1 in 590
African / African American	~21k	1 in 64	1 in 930
East Asian	~20k	1 in 55	1 in 1,100
Ashkenazi Jewish	~13k	1 in 170	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 58	1 in 360

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): 4 of 5 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 5.? see exons ↓