DNAJB4

Chr 1AR

DnaJ heat shock protein family (Hsp40) member B4

ENSG00000162616 UniProt: Q9UDY4 OMIM: 611327

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Probable chaperone. Stimulates ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B (in vitro) (PubMed:24318877)

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Congenital myopathy 21 with early respiratory failureMIM #620326

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Congenital myopathy 21 with early respiratory failure; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.83

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.83LOEUF

pLI 0.016

Z-score 2.00

OE 0.39 (0.20–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.21Z-score

OE missense 0.75 (0.65–0.86)

138 obs / 184.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.20–0.83)

0≤0.351.4

Missense OE?0.75 (0.65–0.86)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 5 / 12.7Missense obs/exp: 138 / 184.1Syn Z: 0.27

Background carrier burden — how many people carry a rare variant somewhere in DNAJB4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

348 rare PASS variants

Rare truncating (LoF)

1 in 5,600

40 rare PASS variants

Rare synonymous (reference)

1 in 580

146 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DNAJB4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 250	1 in 4,300
South Asian	~43k	1 in 210	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 230	1 in 6,000
European (Finnish)	~27k	1 in 730	≈ 1 in 22,000
Admixed American	~22k	1 in 400	none seen
African / African American	~21k	1 in 160	≈ 1 in 8,400
East Asian	~20k	1 in 210	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 2,200	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 410	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓