MS4A6E

Chr 11

membrane spanning 4-domains A6E

NCBI Gene: 245802 ENSG00000166926 UniProt: Q96DS6 OMIM: 608402

This gene encodes a membrane-spanning protein that may function in signal transduction as part of a multimeric receptor complex, with expression in hematopoietic cells and other tissues. The gene shows low constraint against loss-of-function variants (pLI 0.03, LOEUF 1.31), and no established Mendelian diseases have been definitively linked to MS4A6E mutations in current medical literature. Clinical significance of variants in this gene remains uncertain.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. The gene encoding this protein is localized to 11q12.3, among a cluster of family members. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.31

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.31LOEUF

pLI 0.029

Z-score 1.10

OE 0.51 (0.23–1.31)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.50Z-score

OE missense 1.16 (0.98–1.39)

89 obs / 76.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.51 (0.23–1.31)

0≤0.351.4

Missense OE?1.16 (0.98–1.39)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 3 / 5.9Missense obs/exp: 89 / 76.6Syn Z: -0.67

Background carrier burden — how many people carry a rare variant somewhere in MS4A6E?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 260

196 rare PASS variants

Rare truncating (LoF)

1 in 1,500

35 rare PASS variants

Rare synonymous (reference)

1 in 320

79 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MS4A6E. 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 380	1 in 1,800
South Asian	~43k	1 in 240	1 in 2,200
Remaining (unassigned)	~30k	1 in 290	1 in 2,300
European (Finnish)	~27k	1 in 330	≈ 1 in 27,000
Admixed American	~22k	1 in 250	≈ 1 in 5,600
African / African American	~21k	1 in 250	≈ 1 in 4,400
East Asian	~20k	1 in 210	≈ 1 in 5,000
Ashkenazi Jewish	~13k	≈ 1 in 13,000	none seen
Middle Eastern	~2,884	1 in 210	≈ 1 in 960

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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓