HSPB1

Chr 7AD

heat shock protein family B (small) member 1

Also known as: CMT2F, HEL-S-102, HMN2B, HMND3, HS.76067, HSP27, HSP28, Hsp25

NCBI Gene: 3315 ENSG00000106211 UniProt: P04792

This gene encodes a member of the small heat shock protein (HSP20) family of proteins. In response to environmental stress, the encoded protein translocates from the cytoplasm to the nucleus and functions as a molecular chaperone that promotes the correct folding of other proteins. This protein plays an important role in the differentiation of a wide variety of cell types. Expression of this gene is correlated with poor clinical outcome in multiple human cancers, and the encoded protein may promote cancer cell proliferation and metastasis, while protecting cancer cells from apoptosis. Mutations in this gene have been identified in human patients with Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. [provided by RefSeq, Aug 2017]

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, axonal, type 2FMIM #606595

Neuronopathy, distal hereditary motor, autosomal dominant 3MIM #608634

458

ClinVar variants

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— HSPB1

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Gene-Disease Validity (ClinGen)

Charcot-Marie-Tooth disease axonal type 2F · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

68 Pathogenic / Likely Pathogenic· 236 VUS of 458 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

1.87LOEUF

pLI 0.000

Z-score -0.63

OE 1.26 (0.74–1.87)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

-0.51Z-score

OE missense 1.13 (0.98–1.30)

136 obs / 120.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.26 (0.74–1.87)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.13 (0.98–1.30)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.46

0≤1.21.6

LoF obs/exp: 9 / 7.2Missense obs/exp: 136 / 120.1Syn Z: -2.68