MS4A8

Chr 11

membrane spanning 4-domains A8

Also known as: 4SPAN4, CD20L5, MS4A4, MS4A8B

NCBI Gene: 83661 ENSG00000166959 UniProt: Q9BY19

The protein is a membrane-spanning family member that may function in signal transduction as part of a multimeric receptor complex, with expression in hematopoietic cells and other tissues. This gene shows very low constraint against loss-of-function variants (pLI 0.00002, LOEUF 1.41), and no clear Mendelian disease associations have been established for MS4A8 mutations in pediatric neurology. Currently, there is insufficient evidence to define specific neurological phenotypes or inheritance patterns associated with this gene.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the membrane-spanning 4A gene family. Members of this 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]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.41

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?

1.41LOEUF

pLI 0.000

Z-score 0.63

OE 0.79 (0.46–1.41)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.69Z-score

OE missense 0.84 (0.72–0.97)

120 obs / 143.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.46–1.41)

0≤0.351.4

Missense OE?0.84 (0.72–0.97)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 8 / 10.2Missense obs/exp: 120 / 143.3Syn Z: -0.83

Background carrier burden — how many people carry a rare variant somewhere in MS4A8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

355 rare PASS variants

Rare truncating (LoF)

1 in 3,100

81 rare PASS variants

Rare synonymous (reference)

1 in 770

104 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MS4A8. 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 140	1 in 3,600
South Asian	~43k	1 in 170	1 in 1,100
Remaining (unassigned)	~30k	1 in 130	≈ 1 in 9,900
European (Finnish)	~27k	1 in 650	≈ 1 in 13,000
Admixed American	~22k	1 in 120	1 in 1,200
African / African American	~21k	1 in 110	1 in 3,500
East Asian	~20k	1 in 240	1 in 1,700
Ashkenazi Jewish	~13k	1 in 280	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 170	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): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓