DNAJC19

Chr 3AR

DnaJ heat shock protein family (Hsp40) member C19

Also known as: PAM18, TIM14, TIMM14

NCBI Gene: 131118 ENSG00000205981 UniProt: Q96DA6 OMIM: 608977

This mitochondrial co-chaperone forms a complex with prohibitins to regulate cardiolipin remodeling and is involved in ATP-dependent transport of proteins into the mitochondrial matrix. Autosomal recessive mutations cause 3-methylglutaconic aciduria type V, also known as dilated cardiomyopathy with ataxia syndrome, affecting cardiac and neurological systems. The gene shows relatively low constraint against loss-of-function variants (pLI 0.0006, LOEUF 1.3).

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is thought to be part of a complex involved in the ATP-dependent transport of transit peptide-containing proteins from the inner cell membrane to the mitochondrial matrix. Defects in this gene are a cause of 3-methylglutaconic aciduria type 5 (MGA5), also known as dilated cardiomyopathy with ataxia (DCMA). Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1, 2, 6, 10, 14 and 19. [provided by RefSeq, Jan 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.311 OMIM phenotype

Clinical Summary— DNAJC19

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Gene-Disease Validity (ClinGen)

3-methylglutaconic aciduria type 5 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

24 unique Pathogenic / Likely Pathogenic· 54 VUS of 176 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — DNAJC19

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.31LOEUF

pLI 0.001

Z-score 0.93

OE 0.66 (0.36–1.31)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.88Z-score

OE missense 0.69 (0.54–0.89)

44 obs / 63.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.36–1.31)

0≤0.351.4

Missense OE?0.69 (0.54–0.89)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 6 / 9.0Missense obs/exp: 44 / 63.7Syn Z: 0.15

This gene — mechanism propensity

0.80top 10%

GOF

0.5562th %ile

LOF

0.2677th %ile

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

DNprediction above median

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.

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

ClinVar Variant Classifications

176 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14

Likely Pathogenic10

VUS54

Likely Benign76

Benign10

Conflicting5

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	0	3	0	14
Likely Pathogenic	9	1	0	0	10
VUS	6	43	5	0	54
Likely Benign	0	0	48	28	76
Benign	0	0	10	0	10
Conflicting	—				5
Total	26	44	66	28	169

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap DNAJC19 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →