MS4A4E

Chr 11

membrane spanning 4-domains A4E

NCBI Gene: 643680 ENSG00000214787 UniProt: Q96PG1

The protein contains four transmembrane domains with cytoplasmic N- and C-terminal regions, though its specific cellular function remains unclear. This gene shows very low constraint against loss-of-function variants (pLI 0.001, LOEUF 1.89), and no definitive disease associations have been established for MS4A4E mutations in pediatric neurology.

ResearchSummary from RefSeq

Most MS4A genes, including MS4A4E, encode proteins with at least 4 potential transmembrane domains and N- and C-terminal cytoplasmic domains encoded by distinct exons.[supplied by OMIM, Apr 2004]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.89

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?

1.89LOEUF

pLI 0.001

Z-score -0.31

OE 1.18 (0.55–1.89)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.21Z-score

OE missense 0.90 (0.69–1.20)

34 obs / 37.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.18 (0.55–1.89)

0≤0.351.4

Missense OE?0.90 (0.69–1.20)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 4 / 3.4Missense obs/exp: 34 / 37.6Syn Z: 0.09

Background carrier burden — how many people carry a rare variant somewhere in MS4A4E?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 49

399 rare PASS variants

Rare truncating (LoF)

1 in 340

88 rare PASS variants

Rare synonymous (reference)

1 in 160

120 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MS4A4E. 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 81	1 in 650
South Asian	~43k	1 in 67	1 in 630
Remaining (unassigned)	~30k	1 in 64	1 in 420
European (Finnish)	~27k	1 in 130	1 in 3,400
Admixed American	~22k	1 in 80	1 in 640
African / African American	~21k	1 in 59	1 in 1,100
East Asian	~20k	1 in 54	≈ 1 in 4,000
Ashkenazi Jewish	~13k	1 in 280	1 in 1,700
Middle Eastern	~2,884	1 in 120	≈ 1 in 880

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): 1 of 8 coding exons well covered in gnomAD exomes; exons 3, 5, 7, 8, 9 poorly covered; exons 4, 6 marginal. Genomes: all 8.? see exons ↓