DNAJB4

Chr 1AR

DnaJ heat shock protein family (Hsp40) member B4

Also known as: CMYO21, CMYP21, DNAJW, DjB4, HLJ1

This gene encodes a molecular chaperone protein that stimulates ATP hydrolysis and assists in protein folding by working with heat shock proteins. Biallelic mutations cause congenital myopathy 21 with early respiratory failure, an autosomal recessive disorder characterized by muscle weakness and significant breathing difficulties from birth. The gene shows relatively low constraint to loss-of-function variation in the general population.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Congenital myopathy 21 with early respiratory failureMIM #620326
AR
0
Active trials
10
Pubs (1 yr)
19
P/LP submissions
16%
P/LP missense
0.83
LOEUF
DN
Mechanism· predicted
Clinical SummaryDNAJB4
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 unique Pathogenic / Likely Pathogenic· 45 VUS of 70 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.016
Z-score 2.00
OE 0.39 (0.200.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.21Z-score
OE missense 0.75 (0.650.86)
138 obs / 184.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.39 (0.200.83)
00.351.4
Missense OE0.75 (0.650.86)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 5 / 12.7Missense obs/exp: 138 / 184.1Syn Z: 0.27
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedDNAJB4-related myopathy with early respiratory failureOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.78top 25%
GOF
0.6053th %ile
LOF
0.2774th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

70 submitted variants in ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic1
VUS45
Likely Benign1
18
Pathogenic
1
Likely Pathogenic
45
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
15
0
18
Likely Pathogenic
0
0
1
0
1
VUS
0
35
10
0
45
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total03827065

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

View in ClinVar →

Protein Context — Lollipop Plot

DNAJB4 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC