DNAJB6

Chr 7AD

DnaJ heat shock protein family (Hsp40) member B6

Also known as: DJ4, DnaJ, HHDJ1, HSJ-2, HSJ2, LGMD1D, LGMD1E, LGMDD1

NCBI Gene: 10049ENSG00000105993UniProt: O75190

This gene encodes a member of the DNAJ protein family. DNAJ family members are characterized by a highly conserved amino acid stretch called the 'J-domain' and function as one of the two major classes of molecular chaperones involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. This family member may also play a role in polyglutamine aggregation in specific neurons. Alternative splicing of this gene results in multiple transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Muscular dystrophy, limb-girdle, autosomal dominant 1MIM #603511
AD
621
ClinVar variants
93
Pathogenic / LP
0.85
pLI score
0
Active trials
Clinical Summary— DNAJB6
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
93 Pathogenic / Likely Pathogenic· 205 VUS of 621 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.40LOEUF
pLI 0.854
Z-score 3.46
OE 0.15 (0.07–0.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.17Z-score
OE missense 0.76 (0.67–0.87)
148 obs / 194.0 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.0.15 (0.07–0.40)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.67–0.87)
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.1.16
0≤1.21.6
LoF obs/exp: 3 / 19.5Missense obs/exp: 148 / 194.0Syn Z: -1.16

ClinVar Variant Classifications

621 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic84
Likely Pathogenic9
VUS205
Likely Benign134
Benign50
Conflicting38
84
Pathogenic
9
Likely Pathogenic
205
VUS
134
Likely Benign
50
Benign
38
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
10
74
0
84
Likely Pathogenic
0
2
7
0
9
VUS
9
132
63
1
205
Likely Benign
0
6
71
57
134
Benign
0
0
49
1
50
Conflicting
—38
Total915026459520

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

View in ClinVar →

Protein Context — Lollipop Plot

DNAJB6 · 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

Muscular dystrophy, limb-girdle, autosomal dominant 1

MIM #603511

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Panorama of the distal myopathies.
Savarese M et al.·Acta Myol
2020Review
Clinical, Histopathologic, and Genetic Features of Patients With Myofibrillary and Distal Myopathies: Experience From the Italian Network.
Bortolani S et al.·Neurology
2024Cohort
Mutational and clinical spectrum of myofibrillar myopathy in one center from China.
Wang Q et al.·J Neuromuscul Dis
2024
DNAJB6 is expressed in neurons and oligodendrocytes of the human brain.
Hentze J et al.·Glia
2024
New aspects of myofibrillar myopathies.
Kley RA et al.·Curr Opin Neurol
2016Review
Evaluation of aggrephagy markers in myofibrillar myopathies.
Iannibelli E et al.·Acta Neuropathol Commun
2025
Myofibrillar myopathy in the genomic context.
Fichna JP et al.·J Appl Genet
2018Review
Ubiquitin-related gene markers predict immunotherapy response and prognosis in patients with epithelial ovarian carcinoma.
Luo D et al.·Sci Rep
2024Cohort
DNAJB6b is Downregulated in Synucleinopathies.
Folke J et al.·J Parkinsons Dis
2021
Extracellular chaperone networks and the export of J-domain proteins.
Braun JEA·J Biol Chem
2023Review
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