DNAJC30

Chr 7AR

DnaJ heat shock protein family (Hsp40) member C30

Also known as: LHONAR, LHONAR1, MC1DN38, WBSCR18

NCBI Gene: 84277ENSG00000176410UniProt: Q96LL9

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]

Primary Disease Associations & Inheritance

Leber-like hereditary optic neuropathy, autosomal recessive 1MIM #619382
AR
218
ClinVar variants
170
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— DNAJC30
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
170 Pathogenic / Likely Pathogenic· 41 VUS of 218 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.08Z-score
OE missense 1.26 (1.11–1.43)
174 obs / 138.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.56 (0.25–1.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.26 (1.11–1.43)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.35
0≤1.21.6
LoF obs/exp: 3 / 5.4Missense obs/exp: 174 / 138.3Syn Z: -2.11

ClinVar Variant Classifications

218 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic160
Likely Pathogenic10
VUS41
Likely Benign6
Benign1
160
Pathogenic
10
Likely Pathogenic
41
VUS
6
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
157
0
160
Likely Pathogenic
1
2
7
0
10
VUS
0
36
5
0
41
Likely Benign
0
1
0
5
6
Benign
0
1
0
0
1
Total2421695218

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Leber-like hereditary optic neuropathy, autosomal recessive 1

MIM #619382

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — DNAJC30
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Bioinformatic analysis constructs an optimal prognostic index for survival-related variables (OPISV) based on whole-genome expression data in Glioblastoma.
Pan J et al.·Int J Biol Macromol
2024
Autosomal recessive Leber hereditary optic neuropathy, a new neuro-ophthalmo-genetic paradigm.
Lenaers G et al.·Brain
2023
Expanding the phenotype of DNAJC30-associated Leigh syndrome.
Zawadzka M et al.·Clin Genet
2022Case report
DNAJC30 defect: a frequent cause of recessive Leber hereditary optic neuropathy and Leigh syndrome.
Stenton SL et al.·Brain
2022
Autosomal recessive Leber's hereditary optic neuropathy caused by a homozygous variant in DNAJC30 gene.
Mauring L et al.·Eur J Med Genet
2023
Digenic Leigh syndrome on the background of the m.11778G>A Leber hereditary optic neuropathy variant.
Blickhäuser B et al.·Brain
2024
Impaired complex I repair causes recessive Leber's hereditary optic neuropathy.
Stenton SL et al.·J Clin Invest
2021
Recessive MECR pathogenic variants cause an LHON-like optic neuropathy.
Fiorini C et al.·J Med Genet
2023
DNAJC30 disease-causing gene variants in a large Central European cohort of patients with suspected Leber's hereditary optic neuropathy and optic atrophy.
Kieninger S et al.·J Med Genet
2022Cohort
Prenatal diagnosis, ultrasound findings and pregnancy outcome of 7q11.23 deletion and duplication syndromes: what are the fetal features?
Luo X et al.·BMC Pregnancy Childbirth
2024
Top 10 resultsSearch 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)
2025🔓 Open 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
2025🔓 Open 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
2024🔓 Open 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
2023🔓 Open AccessCohort
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools