DNAJC6

Chr 1AR

DnaJ heat shock protein family (Hsp40) member C6

Also known as: DJC6, PARK19

NCBI Gene: 9829 ENSG00000116675 UniProt: O75061 OMIM: 608375

DNAJC6 encodes auxilin, a co-chaperone protein that recruits HSC70 to promote ATP-dependent clathrin disassembly from coated vesicles and participates in clathrin-mediated endocytosis and synaptic vesicle recycling. Biallelic mutations cause juvenile-onset Parkinson disease 19a and early-onset Parkinson disease 19b with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.22), indicating that complete loss of function is likely incompatible with normal development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

DNAJC6 belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJ proteins may have up to 3 distinct domains: a conserved 70-amino acid J domain, usually at the N terminus, a glycine/phenylalanine (G/F)-rich region, and a cysteine-rich domain containing 4 motifs resembling a zinc finger domain (Ohtsuka and Hata, 2000 [PubMed 11147971]).[supplied by OMIM, Mar 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Parkinson disease 19a, juvenile-onsetMIM #615528

Parkinson disease 19b, early-onsetMIM #615528

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Parkinson disease 19a, juvenile-onset; Parkinson disease 19b, early-onset; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.22

LOEUF· LoF intol.

LOF

Mechanism· predicted

📖

GeneReview available — DNAJC6

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.22LOEUF

pLI 1.000

Z-score 5.70

OE 0.11 (0.05–0.22)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.60Z-score

OE missense 0.80 (0.74–0.87)

424 obs / 527.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.05–0.22)

0≤0.351.4

Missense OE?0.80 (0.74–0.87)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 5 / 47.3Missense obs/exp: 424 / 527.4Syn Z: 0.63

Background carrier burden — how many people carry a rare variant somewhere in DNAJC6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 56

1,154 rare PASS variants

Rare truncating (LoF)

1 in 2,300

95 rare PASS variants

Rare synonymous (reference)

1 in 120

472 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DNAJC6. 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 67	1 in 2,700
South Asian	~43k	1 in 61	1 in 2,400
Remaining (unassigned)	~30k	1 in 63	1 in 5,900
European (Finnish)	~27k	1 in 110	≈ 1 in 6,300
Admixed American	~22k	1 in 59	1 in 2,500
African / African American	~21k	1 in 64	1 in 870
East Asian	~20k	1 in 82	1 in 2,600
Ashkenazi Jewish	~13k	1 in 150	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 73	≈ 1 in 2,800

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): 18 of 19 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 19.? see exons ↓