DNAJC30

Chr 7AR

DnaJ heat shock protein family (Hsp40) member C30

Also known as: LHONAR, LHONAR1, MC1DN38, WBSCR18

NCBI Gene: 84277 ENSG00000176410 UniProt: Q96LL9 OMIM: 618202

This mitochondrial protein regulates cellular respiration by associating with the ATP synthase complex to facilitate ATP synthesis and acts as a chaperone for mitochondrial complex I subunits. Autosomal recessive mutations cause Leber-like hereditary optic neuropathy, primarily affecting the visual system. The gene shows low constraint against loss-of-function variants and is deleted in Williams syndrome.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This intronless gene encodes a member of the DNAJ molecular chaperone homology domain-containing protein family. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.421 OMIM phenotype

Clinical Summary— DNAJC30

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Gene-Disease Validity (ClinGen)

Leber-like hereditary optic neuropathy, autosomal recessive 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 38 VUS of 55 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — DNAJC30

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?

1.42LOEUF

pLI 0.023

Z-score 0.94

OE 0.56 (0.25–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.08Z-score

OE missense 1.26 (1.11–1.43)

174 obs / 138.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.56 (0.25–1.42)

0≤0.351.4

Missense OE?1.26 (1.11–1.43)

0≤0.61.4

Synonymous OE?1.35

0≤1.21.6

LoF obs/exp: 3 / 5.4Missense obs/exp: 174 / 138.3Syn Z: -2.11

This gene — mechanism propensity

0.80top 10%

GOF

0.7027th %ile

LOF

0.1993th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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

55 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic4

VUS38

Likely Benign7

Benign1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	3	0	0	5
Likely Pathogenic	2	2	0	0	4
VUS	0	37	1	0	38
Likely Benign	0	1	0	6	7
Benign	0	1	0	0	1
Total	4	44	1	6	55

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

View in ClinVar →

164 pathogenic / likely-pathogenic (of 168) ClinVar copy-number / structural variants overlap DNAJC30 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →