HSPB3

Chr 5AD

heat shock protein family B (small) member 3

Also known as: DHMN2C, HMN2C, HMND4, HSPL27

NCBI Gene: 8988ENSG00000169271UniProt: Q12988

This gene encodes a muscle-specific small heat shock protein. A mutation in this gene is the cause of autosomal dominant distal hereditary motor neuropathy type 2C.[provided by RefSeq, Sep 2010]

Primary Disease Associations & Inheritance

?Neuronopathy, distal hereditary motor, autosomal dominant 4MIM #613376
AD
100
ClinVar variants
9
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HSPB3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 61 VUS of 100 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.
1.84LOEUF
pLI 0.000
Z-score -0.25
OE 1.11 (0.60–1.84)
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.
0.04Z-score
OE missense 0.99 (0.82–1.19)
80 obs / 80.9 exp
Tolerant

Mild missense constraint

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.1.11 (0.60–1.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.82–1.19)
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.1.11
0≤1.21.6
LoF obs/exp: 6 / 5.4Missense obs/exp: 80 / 80.9Syn Z: -0.49

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS61
Likely Benign18
Benign7
Conflicting5
8
Pathogenic
1
Likely Pathogenic
61
VUS
18
Likely Benign
7
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
1
0
1
VUS
2
38
19
2
61
Likely Benign
0
3
3
12
18
Benign
0
1
4
2
7
Conflicting
—5
Total2423516100

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HSPB3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Neuronopathy, distal hereditary motor, autosomal dominant 4

MIM #613376

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical exome sequencing findings in 1589 patients.
Gorukmez O et al.·Am J Med Genet A
2023Cohort
Evaluation of the Small Heat Shock Protein Family Members HSPB2 and HSPB3 in Bladder Cancer Prognosis and Progression.
Gianniou DD et al.·Int J Mol Sci
2023
The genetics of spinal muscular atrophies.
Wee CD et al.·Curr Opin Neurol
2010Review
Human HspB1, HspB3, HspB5 and HspB8: Shaping these disease factors during vertebrate evolution.
Benndorf R et al.·Cell Stress Chaperones
2022
Small heat shock protein B3 (HSPB3) mutation in an axonal Charcot-Marie-Tooth disease family.
Nam DE et al.·J Peripher Nerv Syst
2018Case report
Mitochondrial dynamics and inherited peripheral nerve diseases.
Pareyson D et al.·Neurosci Lett
2015Review
Genetic and Pharmacological Modulation of Cellular Proteostasis Leads to Partial Functional Rescue of Homocystinuria-Causing Cystathionine-Beta Synthase Variants.
Collard R et al.·Mol Cell Biol
2023Functional
Molecular genetics and mechanisms of disease in distal hereditary motor neuropathies: insights directing future genetic studies.
Drew AP et al.·Curr Mol Med
2011Review
The Importance of Multiple Gene Analysis for Diagnosis and Differential Diagnosis in Charcot Marie Tooth Disease.
Yalcintepe S et al.·Turk Neurosurg
2021
Genetic and Clinical Studies of Peripheral Neuropathies with Three Small Heat Shock Protein Gene Variants in Korea.
Lim SO et al.·Genes (Basel)
2022Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools