DNAJB2

Chr 2AR

DnaJ heat shock protein family (Hsp40) member B2

Also known as: CMT2T, DSMA5, HMNR5, HSJ-1, HSJ1, HSPF3

NCBI Gene: 3300ENSG00000135924UniProt: P25686

This gene is almost exclusively expressed in the brain, mainly in the neuronal layers. It encodes a protein that shows sequence similarity to bacterial DnaJ protein and the yeast homologs. In bacteria, this protein is implicated in protein folding and protein complex dissociation. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2011]

Primary Disease Associations & Inheritance

Neuronopathy, distal hereditary motor, autosomal recessive 5MIM #614881
AR
370
ClinVar variants
55
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DNAJB2
🧬
Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease axonal type 2T · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
55 Pathogenic / Likely Pathogenic· 136 VUS of 370 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.
1.03LOEUF
pLI 0.000
Z-score 1.49
OE 0.59 (0.35–1.03)
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.
0.72Z-score
OE missense 0.86 (0.76–0.97)
174 obs / 202.9 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.0.59 (0.35–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.76–0.97)
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.1.01
0≤1.21.6
LoF obs/exp: 9 / 15.3Missense obs/exp: 174 / 202.9Syn Z: -0.05

ClinVar Variant Classifications

370 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic18
VUS136
Likely Benign155
Benign18
Conflicting6
37
Pathogenic
18
Likely Pathogenic
136
VUS
155
Likely Benign
18
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
32
0
37
Likely Pathogenic
12
2
4
0
18
VUS
1
120
15
0
136
Likely Benign
0
5
75
75
155
Benign
0
1
17
0
18
Conflicting
—6
Total1812814375370

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

View in ClinVar →

Protein Context — Lollipop Plot

DNAJB2 · 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 recessive 5

MIM #614881

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — DNAJB2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Distal hereditary motor neuropathies.
Tazir M et al.·Rev Neurol (Paris)
2024Review
Current advance on distal myopathy genetics.
Ranta-Aho J et al.·Curr Opin Neurol
2024Review
DNAJB2 Attenuates Rosacea Skin Inflammation and Angiogenesis by Inhibiting the Endoplasmic Reticulum Stress-mediated TLR2/Myd88/NF-κB pathway.
Qing Y et al.·Inflammation
2025
DNAJB2-related Charcot-Marie-Tooth disease type 2: Pathomechanism insights and phenotypic spectrum widening.
Saveri P et al.·Eur J Neurol
2022Functional
DNAJB2 c.184C>T mutation associated with distal hereditary motor neuropathy with rimmed vacuolar myopathy.
Liu M et al.·Clin Neuropathol
2022
Polymorphism in Genes Encoding HSP40 Family Proteins is Associated with Ischemic Stroke Risk and Brain Infarct Size: A Pilot Study.
Kobzeva KA et al.·J Integr Neurosci
2024
Broadening the Clinical Spectrum of Axonal Hereditary Neuropathies: A Comparative Case Study on DNAJB2- and HINT1-Related Disease.
Bjelica B et al.·J Peripher Nerv Syst
2026
Molecular analysis and clinical diversity of distal hereditary motor neuropathy.
Liu X et al.·Eur J Neurol
2020
Mitochondrial dynamics and inherited peripheral nerve diseases.
Pareyson D et al.·Neurosci Lett
2015Review
Extension of the DNAJB2a isoform in a dominant neuromyopathy family.
Sarparanta J et al.·Hum Mol Genet
2023
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