MS4A7

Chr 11

membrane spanning 4-domains A7

Also known as: 4SPAN2, CD20L4, CFFM4, MS4A8

NCBI Gene: 58475 ENSG00000166927 UniProt: Q9GZW8

The protein is a membrane-spanning receptor component involved in signal transduction in monocytic cells and may function as part of a multimeric receptor complex. MS4A7 is highly tolerant to loss-of-function variants based on population data, with no established Mendelian disease associations currently reported in clinical databases. The gene shows specific expression in hematopoietic cells and is part of a gene cluster on chromosome 11q12.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the membrane-spanning 4A gene family, members of which are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns in hematopoietic cells and nonlymphoid tissues. This family member is associated with mature cellular function in the monocytic lineage, and it may be a component of a receptor complex involved in signal transduction. This gene is localized to 11q12, in a cluster of other family members. At least four alternatively spliced transcript variants encoding two distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.51

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?

1.51LOEUF

pLI 0.000

Z-score 0.38

OE 0.87 (0.52–1.51)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.02Z-score

OE missense 1.01 (0.87–1.17)

123 obs / 122.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.87 (0.52–1.51)

0≤0.351.4

Missense OE?1.01 (0.87–1.17)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 9 / 10.3Missense obs/exp: 123 / 122.2Syn Z: 0.18

Background carrier burden — how many people carry a rare variant somewhere in MS4A7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 99

291 rare PASS variants

Rare truncating (LoF)

1 in 530

77 rare PASS variants

Rare synonymous (reference)

1 in 780

119 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MS4A7. 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 200	1 in 2,000
South Asian	~43k	1 in 82	1 in 1,300
Remaining (unassigned)	~30k	1 in 130	1 in 340
European (Finnish)	~27k	1 in 240	≈ 1 in 27,000
Admixed American	~22k	1 in 200	1 in 750
African / African American	~21k	1 in 130	1 in 1,600
East Asian	~20k	1 in 170	1 in 2,100
Ashkenazi Jewish	~13k	1 in 200	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 180	1 in 300

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 ↓