DNAJC1

Chr 10

DnaJ heat shock protein family (Hsp40) member C1

Also known as: DNAJL1, ERdj1, HTJ1, MTJ1

NCBI Gene: 64215 ENSG00000136770 UniProt: Q96KC8 OMIM: 611207

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.

OMIM ResearchSummary from RefSeq, UniProt

The membrane protein encoded by this gene is a DNAJ-like heat shock protein that binds the molecular chaperone BiP. In addition, the encoded protein contains two SANT domains that have been shown to bind serpin alpha1-antichymotrypsin and inter-alpha trypsin inhibitor heavy chain 4. [provided by RefSeq, Jul 2016]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.82

LOEUF

Multiple*

Mechanism· predicted

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 OE?0.55 (0.38–0.82)

0≤0.351.4

Missense OE?0.91 (0.82–1.01)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 18 / 32.5Missense obs/exp: 258 / 282.1Syn Z: 1.13

Background carrier burden — how many people carry a rare variant somewhere in DNAJC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

753 rare PASS variants

Rare truncating (LoF)

1 in 1,200

140 rare PASS variants

Rare synonymous (reference)

1 in 240

276 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DNAJC1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 270
South Asian	~43k	1 in 63	1 in 1,500
Remaining (unassigned)	~30k	1 in 84	1 in 2,300
European (Finnish)	~27k	1 in 570	1 in 320
Admixed American	~22k	1 in 65	1 in 610
African / African American	~21k	1 in 79	1 in 1,600
East Asian	~20k	1 in 88	1 in 740
Ashkenazi Jewish	~13k	1 in 640	1 in 1,000
Middle Eastern	~2,884	1 in 120	≈ 1 in 850

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 12 coding exons well covered in gnomAD exomes; exons 1, 7, 8 marginal. Genomes: all 12.? see exons ↓