DNAJC30

Chr 7AR

DnaJ heat shock protein family (Hsp40) member C30

Also known as: LHONAR, LHONAR1, MC1DN38, WBSCR18

NCBI Gene: 84277ENSG00000176410UniProt: Q96LL9OMIM: 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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
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
172 unique Pathogenic / Likely Pathogenic· 42 VUS of 222 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 OE0.56 (0.25–1.42)
0≤0.351.4
Missense OE1.26 (1.11–1.43)
0≤0.61.4
Synonymous OE1.35
0≤1.21.6
LoF obs/exp: 3 / 5.4Missense obs/exp: 174 / 138.3Syn Z: -2.11
DN
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

222 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic162
Likely Pathogenic10
VUS42
Likely Benign7
Benign1
162
Pathogenic
10
Likely Pathogenic
42
VUS
7
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
3
157
0
162
Likely Pathogenic
2
2
6
0
10
VUS
0
37
5
0
42
Likely Benign
0
1
0
6
7
Benign
0
1
0
0
1
Total4441686222

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

View in ClinVar →

Protein Context — Lollipop Plot

DNAJC30 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
First Case in Lithuania of an Autosomal Recessive Mutation in the DNAJC30 Gene as a Cause of Leber's Hereditary Optic Neuropathy.
Sereikaite L et al.·Genes (Basel)
2025Open Access
DNAJC30 Mutation in a Patient with Coexisting Leber's Hereditary Optic Neuropathy and Multiple Sclerosis (Harding's Syndrome): A Case Report.
KamaliZonouzi S et al.·Case Rep Ophthalmol
2025Open AccessCase report
An Unusual Presentation of Leber Hereditary Optic Neuropathy-Plus Case Caused by a Novel DNAJC30 Variant.
Şenol HB et al.·Am J Med Genet A
2025
Co-occurrence of glial fibrillary acidic protein astrocytopathy in a patient with Leber's hereditary optic neuropathy due to DNAJC30 mutations.
Giannoccaro MP et al.·Eur J Neurol
2024Open Access
DNAJC30 Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish Patients.
Skorczyk-Werner A et al.·Int J Mol Sci
2023Open AccessCohort
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients