B2M

Chr 15ADAR

beta-2-microglobulin

Also known as: AMYLD6, IMD43, MHC1D4

NCBI Gene: 567 ENSG00000166710 UniProt: P61769 OMIM: 109700

This gene encodes a serum protein found in association with the major histocompatibility complex (MHC) class I heavy chain on the surface of nearly all nucleated cells. The protein has a predominantly beta-pleated sheet structure that can form amyloid fibrils in some pathological conditions. The encoded antimicrobial protein displays antibacterial activity in amniotic fluid. A mutation in this gene has been shown to result in hypercatabolic hypoproteinemia.[provided by RefSeq, Aug 2014]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Amyloidosis, hereditary systemic 6MIM #620659

Immunodeficiency 43MIM #241600

Clinical highlights

Gene–disease validity (ClinGen)

not for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

291

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.71

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — B2M

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.71LOEUF

pLI 0.562

Z-score 2.04

OE 0.15 (0.05–0.71)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

0.81Z-score

OE missense 0.71 (0.55–0.91)

43 obs / 60.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.15 (0.05–0.71)

0≤0.351.4

Missense OE?0.71 (0.55–0.91)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 1 / 6.7Missense obs/exp: 43 / 60.8Syn Z: 0.42

Background carrier burden — how many people carry a rare variant somewhere in B2M?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,400

117 rare PASS variants

Rare truncating (LoF)

1 in 32,000

10 rare PASS variants

Rare synonymous (reference)

1 in 1,100

48 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for B2M. 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 1,500	1 in 20,000
South Asian	~43k	1 in 810	none seen
Remaining (unassigned)	~30k	1 in 1,500	≈ 1 in 30,000
European (Finnish)	~27k	1 in 3,000	none seen
Admixed American	~22k	1 in 660	none seen
African / African American	~21k	1 in 970	none seen
East Asian	~20k	1 in 1,400	none seen
Ashkenazi Jewish	~13k	1 in 2,200	none seen
Middle Eastern	~2,884	≈ 1 in 960	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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓