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: O75190OMIM: 611332

The DNAJB6 protein functions as a molecular chaperone involved in protein folding and oligomeric protein complex assembly, and may regulate polyglutamine aggregation in neurons. Mutations cause autosomal dominant limb-girdle muscular dystrophy type 1 through an unknown pathogenic mechanism. The high pLI score (0.85) and low LOEUF score (0.40) indicate this gene is highly intolerant to loss-of-function variants.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismADLOEUF 0.401 OMIM phenotype
Clinical Summary— DNAJB6
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Gene-Disease Validity (ClinGen)
muscular dystrophy, limb-girdle, autosomal dominant · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.
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ClinVar Variants
55 unique Pathogenic / Likely Pathogenic· 191 VUS of 422 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — DNAJB6
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
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
1.17Z-score
OE missense 0.76 (0.67–0.87)
148 obs / 194.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.15 (0.07–0.40)
0≤0.351.4
Missense OE0.76 (0.67–0.87)
0≤0.61.4
Synonymous OE1.16
0≤1.21.6
LoF obs/exp: 3 / 19.5Missense obs/exp: 148 / 194.0Syn Z: -1.16
DN
0.7035th %ile
GOF
0.4480th %ile
LOF
0.51top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median · 1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNFurthermore, immunofluorescence analyses and filter trap assay demonstrated that the c.287C>T (p.Pro96Leu) mutation possessed a dominant negative effect on the anti-aggregation function of DNAJB6 protein.PMID:28233300

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

422 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic2
VUS191
Likely Benign140
Benign20
Conflicting4
53
Pathogenic
2
Likely Pathogenic
191
VUS
140
Likely Benign
20
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
8
45
0
53
Likely Pathogenic
0
1
1
0
2
VUS
16
141
32
2
191
Likely Benign
0
5
73
62
140
Benign
0
0
18
2
20
Conflicting
—4
Total1615516966410

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients