MS4A2

Chr 11

membrane spanning 4-domains A2

Also known as: APY, ATOPY, FCER1B, FCERI, IGEL, IGER, IGHER

NCBI Gene: 2206 ENSG00000149534 UniProt: Q01362

The allergic response involves the binding of allergen to receptor-bound IgE followed by cell activation and the release of mediators responsible for the manifestations of allergy. The IgE-receptor, a tetramer composed of an alpha, beta, and 2 disulfide-linked gamma chains, is found on the surface of mast cells and basophils. This gene encodes the beta subunit of the high affinity IgE receptor which is 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. This family member is localized to 11q12, among a cluster of membrane-spanning 4A gene family members. Alternative splicing results in multiple transcript variants encoding distinct proteins. Additional transcript variants have been described but require experimental validation. [provided by RefSeq, Mar 2012]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.73

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?

1.73LOEUF

pLI 0.000

Z-score -0.33

OE 1.11 (0.71–1.73)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.31Z-score

OE missense 1.08 (0.94–1.25)

133 obs / 123.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.11 (0.71–1.73)

0≤0.351.4

Missense OE?1.08 (0.94–1.25)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 12 / 10.8Missense obs/exp: 133 / 123.3Syn Z: -0.68

Background carrier burden — how many people carry a rare variant somewhere in MS4A2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

302 rare PASS variants

Rare truncating (LoF)

1 in 730

71 rare PASS variants

Rare synonymous (reference)

1 in 410

120 rare PASS variants

Rare missense and truncating variants are carried at similar rates in MS4A2; 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 250	1 in 390
South Asian	~43k	1 in 150	1 in 1,500
Remaining (unassigned)	~30k	1 in 100	1 in 200
European (Finnish)	~27k	1 in 3,000	≈ 1 in 27,000
Admixed American	~22k	1 in 200	1 in 870
African / African American	~21k	1 in 230	1 in 500
East Asian	~20k	1 in 140	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 450	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 180	≈ 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 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓