DNAJC1

Chr 10

DnaJ heat shock protein family (Hsp40) member C1

Also known as: DNAJL1, ERdj1, HTJ1, MTJ1

NCBI Gene: 64215ENSG00000136770UniProt: Q96KC8

This gene encodes a membrane protein that functions as a DNAJ-like heat shock protein, binding the molecular chaperone BiP and containing SANT domains that interact with specific serpins. Mutations cause autosomal recessive neurodegeneration with brain iron accumulation (NBIA), typically presenting in childhood with dystonia, spasticity, and progressive movement disorders. The gene shows very low constraint against loss-of-function variants (pLI near 0), consistent with its recessive inheritance pattern.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
9
P/LP submissions
0%
P/LP missense
0.82
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— DNAJC1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 78 VUS of 110 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.82LOEUF
pLI 0.000
Z-score 2.35
OE 0.55 (0.38–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.51Z-score
OE missense 0.91 (0.82–1.01)
258 obs / 282.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.55 (0.38–0.82)
0≤0.351.4
Missense OE0.91 (0.82–1.01)
0≤0.61.4
Synonymous OE0.86
0≤1.21.6
LoF obs/exp: 18 / 32.5Missense obs/exp: 258 / 282.1Syn Z: 1.13
DN
0.6743th %ile
GOF
0.7126th %ile
LOF
0.2872th %ile

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

GOFprediction above median
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

110 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS78
Likely Benign6
Benign1
8
Pathogenic
1
Likely Pathogenic
78
VUS
6
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
1
0
1
VUS
0
71
7
0
78
Likely Benign
0
4
0
2
6
Benign
0
0
1
0
1
Total07517294

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

View in ClinVar →

Protein Context — Lollipop Plot

DNAJC1 · protein map & ClinVar variants

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

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 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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