DNAJC12

Chr 10AR

DnaJ heat shock protein family (Hsp40) member C12

Also known as: HPANBH4, JDP1

NCBI Gene: 56521 ENSG00000108176 UniProt: Q9UKB3 OMIM: 606060

This gene encodes a co-chaperone that facilitates proper folding of biopterin-dependent aromatic amino acid hydroxylases including phenylalanine-4-hydroxylase, tyrosine 3-monooxygenase, and tryptophan hydroxylases. Mutations cause autosomal recessive mild hyperphenylalaninemia that is non-BH4-deficient, affecting amino acid metabolism pathways critical for neurotransmitter synthesis.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of a subclass of the HSP40/DnaJ protein family. Members of this family of proteins are associated with complex assembly, protein folding, and export. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.341 OMIM phenotype

Clinical Summary— DNAJC12

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Gene-Disease Validity (ClinGen)

hyperphenylalaninemia due to DNAJC12 deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

23 unique Pathogenic / Likely Pathogenic· 47 VUS of 123 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — DNAJC12

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?

1.34LOEUF

pLI 0.000

Z-score 0.69

OE 0.79 (0.49–1.34)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.06Z-score

OE missense 0.98 (0.84–1.16)

104 obs / 105.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.49–1.34)

0≤0.351.4

Missense OE?0.98 (0.84–1.16)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 10 / 12.6Missense obs/exp: 104 / 105.8Syn Z: 0.08

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongDNAJC12-related hyperphenylalaninemia, dystonia, and intellectual disabilityLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6648th %ile

GOF

0.79top 25%

LOF

0.2484th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

123 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17

Likely Pathogenic6

VUS47

Likely Benign30

Benign20

Conflicting3

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	14	2	1	0	17
Likely Pathogenic	5	1	0	0	6
VUS	0	45	1	1	47
Likely Benign	0	2	14	14	30
Benign	0	2	14	4	20
Conflicting	—				3
Total	19	52	30	19	123

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap DNAJC12 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →