DNAJC15

Chr 13

DnaJ heat shock protein family (Hsp40) member C15

Also known as: DNAJD1, HSD18, MCJ

NCBI Gene: 29103 ENSG00000120675 UniProt: Q9Y5T4

DNAJC15 encodes a protein that regulates mitochondrial respiratory chain activity and facilitates protein import into the mitochondrial matrix by stimulating HSPA9 ATPase activity. Mutations cause autosomal recessive spastic paraplegia, developmental delay, and seizures with onset in infancy or early childhood. The gene shows minimal constraint against loss-of-function variants.

ResearchSummary from RefSeq, UniProt

Predicted to enable ATPase activator activity. Predicted to be involved in protein import into mitochondrial matrix. Predicted to act upstream of or within several processes, including cellular response to starvation; negative regulation of mitochondrial electron transport, NADH to ubiquinone; and negative regulation of protein-containing complex assembly. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.89

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.89LOEUF

pLI 0.000

Z-score -1.03

OE 1.36 (0.87–1.89)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.42Z-score

OE missense 1.13 (0.95–1.35)

91 obs / 80.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.36 (0.87–1.89)

0≤0.351.4

Missense OE?1.13 (0.95–1.35)

0≤0.61.4

Synonymous OE?1.34

0≤1.21.6

LoF obs/exp: 13 / 9.6Missense obs/exp: 91 / 80.4Syn Z: -1.42

Background carrier burden — how many people carry a rare variant somewhere in DNAJC15?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

222 rare PASS variants

Rare truncating (LoF)

1 in 1,600

63 rare PASS variants

Rare synonymous (reference)

1 in 380

81 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DNAJC15. 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 320	1 in 1,500
South Asian	~43k	1 in 290	1 in 770
Remaining (unassigned)	~30k	1 in 340	1 in 1,700
European (Finnish)	~27k	1 in 2,900	≈ 1 in 13,000
Admixed American	~22k	1 in 290	1 in 2,700
African / African American	~21k	1 in 180	≈ 1 in 5,800
East Asian	~20k	1 in 310	1 in 1,300
Ashkenazi Jewish	~13k	1 in 470	none seen
Middle Eastern	~2,884	1 in 360	1 in 380

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 ↓