DNAJC12

Chr 10AR

DnaJ heat shock protein family (Hsp40) member C12

Also known as: HPANBH4, JDP1

NCBI Gene: 56521ENSG00000108176UniProt: Q9UKB3

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]

Primary Disease Associations & Inheritance

Hyperphenylalaninemia, mild, non-BH4-deficientMIM #617384
AR
145
ClinVar variants
40
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DNAJC12
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 Pathogenic / Likely Pathogenic· 51 VUS of 145 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.
1.34LOEUF
pLI 0.000
Z-score 0.69
OE 0.79 (0.49–1.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?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.
0.06Z-score
OE missense 0.98 (0.84–1.16)
104 obs / 105.8 exp
Tolerant

Mild missense constraint

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.0.79 (0.49–1.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.84–1.16)
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.0.98
0≤1.21.6
LoF obs/exp: 10 / 12.6Missense obs/exp: 104 / 105.8Syn Z: 0.08

ClinVar Variant Classifications

145 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic8
VUS51
Likely Benign30
Benign20
Conflicting3
32
Pathogenic
8
Likely Pathogenic
51
VUS
30
Likely Benign
20
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
2
19
0
32
Likely Pathogenic
3
1
4
0
8
VUS
0
45
5
1
51
Likely Benign
0
2
14
14
30
Benign
0
2
14
4
20
Conflicting
—3
Total14525619144

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

View in ClinVar →

Protein Context — Lollipop Plot

DNAJC12 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DNAJC12-related hyperphenylalaninemia, dystonia, and intellectual disability

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hyperphenylalaninemia, mild, non-BH4-deficient

MIM #617384

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Value of genetic analysis for confirming inborn errors of metabolism detected through the Spanish neonatal screening program.
Navarrete R et al.·Eur J Hum Genet
2019
DNAJC12 in Monoamine Metabolism, Neurodevelopment, and Neurodegeneration.
Deng IB et al.·Mov Disord
2024Review
Structural recognition and stabilization of tyrosine hydroxylase by the J-domain protein DNAJC12.
Tai MDS et al.·Nat Commun
2025
Impaired cognitive function and decreased monoamine neurotransmitters in the DNAJC12 gene knockout mouse model.
Wang S et al.·Orphanet J Rare Dis
2025Functional
PAH deficient pathology in humanized c.1066-11G>A phenylketonuria mice.
Martínez-Pizarro A et al.·Hum Mol Genet
2024
Restless legs syndrome in DNAJC12 deficiency.
Porta F et al.·Neurol Sci
2023
Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia.
Gallego D et al.·Hum Mutat
2020
DNAJC12 downregulation induces neuroblastoma progression via increased histone H4K5 lactylation.
Yang Y et al.·J Mol Cell Biol
2025
DNAJC12 and dopa-responsive nonprogressive parkinsonism.
Straniero L et al.·Ann Neurol
2017
Developmental delay and non-phenylketonuria (PKU) hyperphenylalaninemia in DNAJC12 deficiency: Case and approach.
Wong RSH et al.·Brain Dev
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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