MS4A5

Chr 11

membrane spanning 4-domains A5

Also known as: CD20-L2, CD20L2, TETM4

NCBI Gene: 64232 ENSG00000166930 UniProt: Q9H3V2

This protein is a membrane-spanning protein that may function in signal transduction as part of a multimeric receptor complex. The gene is highly constrained against loss-of-function variants, but no definitive disease associations have been established in the provided clinical data. MS4A5 belongs to a gene family with unique expression patterns in hematopoietic and nonlymphoid tissues, though this specific member is not expressed in hematopoietic cells.

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. Though this member is not expressed in hematopoietic cells specifically, it may be involved in signal transduction like many of its related family members. The gene encoding this protein is localized to 11q12, among a cluster of family members. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.44

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?

1.44LOEUF

pLI 0.000

Z-score 0.69

OE 0.74 (0.40–1.44)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.09Z-score

OE missense 0.97 (0.82–1.15)

95 obs / 97.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.40–1.44)

0≤0.351.4

Missense OE?0.97 (0.82–1.15)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 6 / 8.1Missense obs/exp: 95 / 97.6Syn Z: 0.71

Background carrier burden — how many people carry a rare variant somewhere in MS4A5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 310

256 rare PASS variants

Rare truncating (LoF)

1 in 1,500

54 rare PASS variants

Rare synonymous (reference)

1 in 570

82 rare PASS variants

Rare missense and truncating variants are carried at similar rates in MS4A5; this gene does not show strong loss-of-function constraint by this measure. 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 440	1 in 1,700
South Asian	~43k	1 in 260	1 in 1,400
Remaining (unassigned)	~30k	1 in 230	1 in 570
European (Finnish)	~27k	1 in 760	≈ 1 in 8,900
Admixed American	~22k	1 in 340	1 in 3,000
African / African American	~21k	1 in 240	1 in 1,800
East Asian	~20k	1 in 180	1 in 1,300
Ashkenazi Jewish	~13k	1 in 1,800	none seen
Middle Eastern	~2,884	1 in 160	none seen

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