HSPB2

Chr 11

heat shock protein family B (small) member 2

Also known as: HSP27, Hs.78846, LOH11CR1K, MKBP

NCBI Gene: 3316 ENSG00000170276 UniProt: Q16082

The protein encoded by this gene belongs to the superfamily of small heat-shock proteins containing a conservative alpha-crystallin domain at the C-terminal part of the molecule. The protein is expressed preferentially in the heart and skeletal muscle. This protein regulates Myotonic Dystrophy Protein Kinase, which plays an important role in maintenance of muscle structure and function. [provided by RefSeq, Dec 2012]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.48

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?

1.48LOEUF

pLI 0.000

Z-score 0.63

OE 0.76 (0.41–1.48)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.52Z-score

OE missense 0.87 (0.74–1.02)

103 obs / 118.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.76 (0.41–1.48)

0≤0.351.4

Missense OE?0.87 (0.74–1.02)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 6 / 7.9Missense obs/exp: 103 / 118.9Syn Z: -0.17

Background carrier burden — how many people carry a rare variant somewhere in HSPB2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

254 rare PASS variants

Rare truncating (LoF)

1 in 6,500

36 rare PASS variants

Rare synonymous (reference)

1 in 890

117 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HSPB2. 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 300	1 in 8,500
South Asian	~43k	1 in 350	1 in 1,500
Remaining (unassigned)	~30k	1 in 240	≈ 1 in 10,000
European (Finnish)	~27k	1 in 1,400	≈ 1 in 6,500
Admixed American	~22k	1 in 300	≈ 1 in 4,500
African / African American	~21k	1 in 180	1 in 3,600
East Asian	~20k	1 in 380	≈ 1 in 4,900
Ashkenazi Jewish	~13k	1 in 520	none seen
Middle Eastern	~2,884	1 in 390	≈ 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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓