DNAJC4

Chr 11

DnaJ heat shock protein family (Hsp40) member C4

Also known as: DANJC4, HSPF2, MCG18

NCBI Gene: 3338 ENSG00000110011 UniProt: Q9NNZ3 OMIM: 604189

The DNAJC4 protein binds unfolded proteins and is involved in protein folding and cellular responses to misfolded proteins. Mutations cause autosomal recessive spinal muscular atrophy with microcephaly and calcifications, characterized by early-onset motor neuron degeneration, intellectual disability, and brain calcifications. This gene is not highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq

Predicted to enable unfolded protein binding activity. Predicted to be involved in protein folding and response to unfolded protein. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.73

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.73LOEUF

pLI 0.000

Z-score -0.44

OE 1.14 (0.75–1.73)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.13Z-score

OE missense 1.03 (0.90–1.18)

149 obs / 144.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.14 (0.75–1.73)

0≤0.351.4

Missense OE?1.03 (0.90–1.18)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 14 / 12.3Missense obs/exp: 149 / 144.6Syn Z: 0.21

Background carrier burden — how many people carry a rare variant somewhere in DNAJC4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

415 rare PASS variants

Rare truncating (LoF)

1 in 990

89 rare PASS variants

Rare synonymous (reference)

1 in 260

132 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DNAJC4. 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 170	1 in 1,300
South Asian	~43k	1 in 110	1 in 360
Remaining (unassigned)	~30k	1 in 150	1 in 770
European (Finnish)	~27k	1 in 590	1 in 4,100
Admixed American	~22k	1 in 180	1 in 660
African / African American	~21k	1 in 100	1 in 520
East Asian	~20k	1 in 93	1 in 990
Ashkenazi Jewish	~13k	1 in 1,200	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 160	≈ 1 in 930

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 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓