DNAJC12

Summary

DNAJC12 (DnaJ heat shock protein family (Hsp40) member C12, HGNC:28908) is a protein-coding gene on chromosome 10q21.3, encoding DnaJ homolog subfamily C member 12 (Q9UKB3). Probable co-chaperone that participates in the proper folding of biopterin-dependent aromatic amino acid hydroxylases, which include phenylalanine-4-hydroxylase (PAH), tyrosine 3-monooxygenase (TH) and peripheral and neuronal tryptophan hydroxylases (TPH1 and TPH2).

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.

Source: NCBI Gene 56521 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyperphenylalaninemia due to DNAJC12 deficiency (Definitive, ClinGen)
• GWAS associations: 5
• Clinical variants (ClinVar): 125 total — 17 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 15
• MANE Select transcript: NM_021800

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28908
Approved symbol	DNAJC12
Name	DnaJ heat shock protein family (Hsp40) member C12
Location	10q21.3
Locus type	gene with protein product
Status	Approved
Aliases	JDP1
Ensembl gene	ENSG00000108176
Ensembl biotype	protein_coding
OMIM	606060
Entrez	56521

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 nonsense_mediated_decay

ENST00000225171, ENST00000339758, ENST00000480180, ENST00000480963, ENST00000483798, ENST00000857833, ENST00000857834

RefSeq mRNA: 2 — MANE Select: NM_021800 NM_021800, NM_201262

CCDS: CCDS7271, CCDS7272

Canonical transcript exons

ENST00000225171 — 5 exons

Exon	Start	End
ENSE00000834117	67796669	67797210
ENSE00001887057	67837934	67838188
ENSE00003545459	67805583	67805787
ENSE00003559505	67823314	67823392
ENSE00003596915	67811524	67811663

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 98.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1418 / max 146.0412, expressed in 991 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109723	2.9757	743
109721	1.3004	365
109725	1.1032	399
109724	0.3436	169
109722	0.2336	113
205882	0.1853	93

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	98.04	gold quality
cerebellar vermis	UBERON:0004720	97.90	gold quality
cerebellar cortex	UBERON:0002129	96.25	gold quality
cerebellar hemisphere	UBERON:0002245	96.22	gold quality
cerebellum	UBERON:0002037	96.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.53	gold quality
substantia nigra pars compacta	UBERON:0001965	94.93	gold quality
pons	UBERON:0000988	94.75	gold quality
type B pancreatic cell	CL:0000169	94.73	gold quality
CA1 field of hippocampus	UBERON:0003881	94.67	gold quality
right adrenal gland	UBERON:0001233	94.48	gold quality
left adrenal gland	UBERON:0001234	94.22	gold quality
right adrenal gland cortex	UBERON:0035827	94.21	gold quality
adrenal cortex	UBERON:0001235	94.03	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.02	gold quality
hypothalamus	UBERON:0001898	94.00	gold quality
superior vestibular nucleus	UBERON:0007227	93.95	gold quality
nephron tubule	UBERON:0001231	93.85	gold quality
left adrenal gland cortex	UBERON:0035825	93.83	gold quality
right lobe of liver	UBERON:0001114	93.60	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.46	gold quality
pancreas	UBERON:0001264	93.32	gold quality
lateral globus pallidus	UBERON:0002476	93.22	gold quality
adrenal gland	UBERON:0002369	93.21	gold quality
entorhinal cortex	UBERON:0002728	92.92	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.87	gold quality
body of pancreas	UBERON:0001150	92.67	gold quality
nucleus accumbens	UBERON:0001882	92.61	gold quality
liver	UBERON:0002107	92.54	gold quality
substantia nigra	UBERON:0002038	92.49	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-83139	yes	614.59
E-CURD-114	yes	12.66
E-GEOD-81547	yes	10.41
E-GEOD-125970	yes	4.96
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB3L4

miRNA regulators (miRDB)

35 targeting DNAJC12, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-6884-3P	98.05	65.32	750
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-6529-5P	97.85	66.47	673

Literature-anchored findings (GeneRIF, showing 17)

• JDP1 is a estrogen target gene and that its expression might be used as a marker of the estrogen transactivation activity (PMID:16391838)
• the endogenous DNAJC12 and Hsc70 proteins interact in LNCaP cells. (PMID:24122553)
• High expression of DNAJC12 correlates with poor prognosis for rectal cancer. (PMID:25805104)
• We report biallelic mutations of DNAJC12 in six affected individuals from four families with hyperphenylalaninemia and dopamine and serotonin deficiencies not caused by mutations in phenylalanine hydroxylase or any known tetrahydrobiopterin metabolism genes. (PMID:28132689)
• The results of this study suggest that DNAJC12 mutations (absent in 500 early-onset patients with Parkinson’s disease) rarely cause dopa-responsive nonprogressive parkinsonism in adulthood. (PMID:28892570)
• Molecular diagnostics for DNAJC12 variants are thus mandatory in all patients in which deficiencies of PAH and BH4 are genetically excluded. (PMID:29174366)
• DNAJC12 mutation is not a risk factor of Parkinson’s disease in Chinese Han population. (PMID:29801756)
• DNAJC12 mutation was identified in two siblings with developmental delay, movement disorder, and mild hyperphenylalaninemia. (PMID:30139987)
• High DNAJC12 expression is associated with gastric Cancer. (PMID:30617870)
• Our results support a role of DNAJC12 in the processing of misfolded ubiquitinated PAH by the ubiquitin-dependent proteasome/autophagy systems and add to the evidence that the DNAJ proteins are important players both for proper folding and degradation of their clients. (PMID:30667134)
• Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia. (PMID:32333439)
• DNAJC12 promotes lung cancer growth by regulating the activation of betacatenin. (PMID:33907820)
• DNACJ12 deficiency in patients with unexplained hyperphenylalaninemia: two new patients and a novel variant. (PMID:34014443)
• Restless legs syndrome in DNAJC12 deficiency. (PMID:36897462)
• A rare cause of hyperphenylalaninemia: four cases from a single family with DNAJC12 deficiency. (PMID:37283250)
• DNAJC12 in Monoamine Metabolism, Neurodevelopment, and Neurodegeneration. (PMID:38014588)
• DNAJC12 causes breast cancer chemotherapy resistance by repressing doxorubicin-induced ferroptosis and apoptosis via activation of AKT. (PMID:38306757)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajc12	ENSDARG00000086691
mus_musculus	Dnajc12	ENSMUSG00000036764
rattus_norvegicus	Dnajc12	ENSRNOG00000051960
drosophila_melanogaster	Csp	FBGN0004179
drosophila_melanogaster	CG10565	FBGN0037051
drosophila_melanogaster	P58IPK	FBGN0037718
drosophila_melanogaster	l(3)80Fg	FBGN0287183
caenorhabditis_elegans		WBGENE00001020
caenorhabditis_elegans		WBGENE00001025
caenorhabditis_elegans		WBGENE00001026
caenorhabditis_elegans		WBGENE00001029
caenorhabditis_elegans		WBGENE00001032
caenorhabditis_elegans	dnj-28	WBGENE00001046
caenorhabditis_elegans		WBGENE00008122

Paralogs (20): DNAJC11 (ENSG00000007923), DNAJC25 (ENSG00000059769), DNAJC10 (ENSG00000077232), DNAJC5 (ENSG00000101152), DNAJC3 (ENSG00000102580), DNAJC17 (ENSG00000104129), DNAJC2 (ENSG00000105821), DNAJC4 (ENSG00000110011), DNAJC16 (ENSG00000116138), DNAJC14 (ENSG00000135392), DNAJC1 (ENSG00000136770), DNAJC13 (ENSG00000138246), DNAJC5B (ENSG00000147570), DNAJC5G (ENSG00000163793), DNAJC7 (ENSG00000168259), DNAJC21 (ENSG00000168724), DNAJC18 (ENSG00000170464), DNAJC24 (ENSG00000170946), DNAJC30 (ENSG00000176410), DNAJC9 (ENSG00000213551)

Protein

Protein identifiers

DnaJ homolog subfamily C member 12 — Q9UKB3 (reviewed: Q9UKB3)

Alternative names: J domain-containing protein 1

All UniProt accessions (5): Q9UKB3, Q6IAH1, S4R368, S4R3E2, S4R3W0

UniProt curated annotations — full annotation on UniProt →

Function. Probable co-chaperone that participates in the proper folding of biopterin-dependent aromatic amino acid hydroxylases, which include phenylalanine-4-hydroxylase (PAH), tyrosine 3-monooxygenase (TH) and peripheral and neuronal tryptophan hydroxylases (TPH1 and TPH2).

Subunit / interactions. Interacts with HSPA8. Interacts with TPH1. Interacts with TPH2.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed at high levels in brain, heart, and testis, and at reduced levels in kidney and stomach.

Disease relevance. Hyperphenylalaninemia, mild, non-BH4-deficient (HPANBH4) [MIM:617384] An autosomal recessive disorder characterized by increased serum phenylalanine, normal BH4 metabolism, and highly variable neurologic defects, including movement abnormalities and intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by ER stress.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UKB3-1	a, JDP1a	yes
Q9UKB3-2	B, JDP1b

RefSeq proteins (2): NP_068572, NP_957714 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001623	DnaJ_domain	Domain
IPR029827	JDP1-like	Family
IPR036869	J_dom_sf	Homologous_superfamily

Pfam: PF00226

UniProt features (25 total): sequence variant 9, helix 5, modified residue 4, splice variant 2, chain 1, domain 1, region of interest 1, turn 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2CTQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKB3-F1	68.84	0.35

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 1, 160, 166, 182

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 202 (showing top): GOZGIT_ESR1_TARGETS_DN, chr10q21, SMID_BREAST_CANCER_RELAPSE_IN_LIVER_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, SMID_BREAST_CANCER_LUMINAL_B_UP, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, MCBRYAN_PUBERTAL_BREAST_5_6WK_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_B_UP, HAN_SATB1_TARGETS_DN, RIGGI_EWING_SARCOMA_PROGENITOR_UP, CHIANG_LIVER_CANCER_SUBCLASS_CTNNB1_UP, ZHAN_MULTIPLE_MYELOMA_CD1_VS_CD2_UP, MULLIGHAN_MLL_SIGNATURE_2_DN, SAMOLS_TARGETS_OF_KHSV_MIRNAS_DN

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

934 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJC12	DNAJB4	Q9UDY4	842
DNAJC12	DNAJB1	P25685	779
DNAJC12	HSPA4	P34932	610
DNAJC12	PAH	P00439	590
DNAJC12	HSPA8	P11142	576
DNAJC12	GCHFR	P30047	558
DNAJC12	DNAJC6	O75061	554
DNAJC12	DNAJC13	O75165	542
DNAJC12	DNAJC25	Q9H1X3	541
DNAJC12	DNAJC1	Q96KC8	525
DNAJC12	QDPR	P09417	506
DNAJC12	DNAJA3	Q96EY1	480
DNAJC12	DNAJC15	Q9Y5T4	476
DNAJC12	ZMYM5	Q9UJ78	465
DNAJC12	AMZ1	Q400G9	460

IntAct

40 interactions, top by confidence:

A	B	Type	Score
SUCLG2	SUCLG1	psi-mi:“MI:0914”(association)	0.690
ARL4C	RGS12	psi-mi:“MI:0914”(association)	0.640
TPH1	DNAJC12	psi-mi:“MI:0915”(physical association)	0.620
ANTXR1	POTEF	psi-mi:“MI:0914”(association)	0.530
EMILIN1	METTL15	psi-mi:“MI:0914”(association)	0.530
LIPH	LRP5	psi-mi:“MI:0914”(association)	0.530
TPH1	YEATS4	psi-mi:“MI:0914”(association)	0.530
ITLN1	HSPA5	psi-mi:“MI:0914”(association)	0.530
PLPPR2	METAP2	psi-mi:“MI:0914”(association)	0.530
TPH2	DNAJC12	psi-mi:“MI:0915”(physical association)	0.400
ERI2	DNAJC12	psi-mi:“MI:0915”(physical association)	0.400
RRAD	DNAJC12	psi-mi:“MI:0915”(physical association)	0.400
TH	MAP3K7	psi-mi:“MI:0914”(association)	0.350
ITLN1	TIPRL	psi-mi:“MI:0914”(association)	0.350
PLPPR2	SEC24D	psi-mi:“MI:0914”(association)	0.350
TOMM20L	ATXN3	psi-mi:“MI:0914”(association)	0.350
PRMT6	TFCP2	psi-mi:“MI:0914”(association)	0.350
ERI2	FLNC	psi-mi:“MI:0914”(association)	0.350
SLC2A4	SMAP2	psi-mi:“MI:0914”(association)	0.350
BRICD5	POTEF	psi-mi:“MI:0914”(association)	0.350
LY86	PLXNB2	psi-mi:“MI:0914”(association)	0.350
PRMT6	TP73	psi-mi:“MI:0914”(association)	0.350
LIPH	B4GALT5	psi-mi:“MI:0914”(association)	0.350

BioGRID (85): DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS)

ESM2 similar proteins: A6QPR9, D2H0H6, E2RDV1, O00472, P40630, Q00059, Q0II87, Q13426, Q149N8, Q15650, Q2TBQ7, Q3UKU1, Q3UY96, Q3ZBU9, Q498D5, Q4H0T5, Q4R8G4, Q5D144, Q5HZY0, Q5M7V7, Q5R4I3, Q5R776, Q5ZKF4, Q6AZF8, Q6DIJ5, Q6ZMV9, Q7L4P6, Q7TPQ3, Q8BSE0, Q8CG73, Q8IWR0, Q8IZC4, Q8NA72, Q8NE18, Q91ZW1, Q92575, Q95LL7, Q96LZ7, Q96QE5, Q99NF3

Diamond homologs: A1BHL1, A1KR91, A1U613, A1V9Q3, A1W0P5, A3MA88, A4SFR5, A5IDK7, A5WBF8, A6Q486, A6QBG7, A6W2D1, A7H2C0, A8FMW6, A9LZV9, B0TYF3, B0VA24, B0VQ00, B2I2G6, B3CP03, B3EE31, B3QPW8, B4S9D0, B5ENA2, B7GV08, B7I2B2, B7J7X8, B8CXL0, B8DQW8, B9FHF3, B9KFK6, B9KH92, C0R562, C1DFM2, C4L8Y4, D2H417, D3ZD82, D3ZSC8, F1RTY8, O14213

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

125 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	2
Uncertain significance	49
Likely benign	28
Benign	20

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1457343	NM_021800.3(DNAJC12):c.502+1G>A	Pathogenic
1459819	NC_000010.10:g.(?69556874)(69565565_?)del	Pathogenic
1921406	NM_021800.3(DNAJC12):c.235C>T (p.Arg79Ter)	Pathogenic
2707876	NM_021800.3(DNAJC12):c.34dup (p.Thr12fs)	Pathogenic
3374776	NM_021800.3(DNAJC12):c.411del (p.Glu138fs)	Pathogenic
3764628	NM_021800.3(DNAJC12):c.157+2T>C	Pathogenic
393301	NM_021800.3(DNAJC12):c.298-968_503-2603del	Pathogenic
393302	NM_021800.3(DNAJC12):c.215G>C (p.Arg72Pro)	Pathogenic
393303	NM_021800.3(DNAJC12):c.158-2A>T	Pathogenic
636261	NM_021800.3(DNAJC12):c.58_59del (p.Gly20fs)	Pathogenic
694072	NM_021800.3(DNAJC12):c.596G>T (p.Ter199Leu)	Pathogenic
694074	NM_021800.3(DNAJC12):c.187A>T (p.Lys63Ter)	Pathogenic
694075	NM_021800.3(DNAJC12):c.79-2A>G	Pathogenic
870653	NM_021800.3(DNAJC12):c.298-2A>C	Pathogenic
870654	NM_021800.3(DNAJC12):c.502+1G>C	Pathogenic
870655	NM_021800.3(DNAJC12):c.524G>A (p.Trp175Ter)	Pathogenic
870656	NM_021800.3(DNAJC12):c.309G>T (p.Trp103Cys)	Pathogenic
1067613	NM_021800.3(DNAJC12):c.78+2T>C	Likely pathogenic
1324284	NM_021800.3(DNAJC12):c.3G>A (p.Met1Ile)	Likely pathogenic

SpliceAI

903 predictions. Top by Δscore:

Variant	Effect	Δscore
10:67797208:AAC:A	acceptor_gain	1.0000
10:67797210:CCTT:C	acceptor_gain	1.0000
10:67798417:CG:C	donor_gain	1.0000
10:67805580:TACCT:T	donor_loss	1.0000
10:67805582:C:CG	donor_loss	1.0000
10:67805785:TGA:T	acceptor_gain	1.0000
10:67805788:C:CC	acceptor_gain	1.0000
10:67805793:T:TC	acceptor_gain	1.0000
10:67805796:A:AC	acceptor_gain	1.0000
10:67805796:A:C	acceptor_gain	1.0000
10:67823308:TCTTA:T	donor_loss	1.0000
10:67823309:CTTA:C	donor_loss	1.0000
10:67823310:TTACC:T	donor_loss	1.0000
10:67823311:TA:T	donor_loss	1.0000
10:67823312:A:AC	donor_gain	1.0000
10:67823312:A:AG	donor_loss	1.0000
10:67823313:C:A	donor_loss	1.0000
10:67823313:C:CC	donor_gain	1.0000
10:67823313:CCAG:C	donor_gain	1.0000
10:67823390:AACC:A	acceptor_loss	1.0000
10:67823391:ACC:A	acceptor_loss	1.0000
10:67823393:CTGA:C	acceptor_loss	1.0000
10:67823394:T:C	acceptor_loss	1.0000
10:67837930:TTAC:T	donor_loss	1.0000
10:67837931:TAC:T	donor_loss	1.0000
10:67837932:A:AC	donor_gain	1.0000
10:67837932:ACCGA:A	donor_loss	1.0000
10:67837933:C:CC	donor_gain	1.0000
10:67837933:C:T	donor_loss	1.0000
10:67797207:AAAC:A	acceptor_gain	0.9900

AlphaMissense

1301 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:67823347:G:C	H42D	0.996
10:67811653:A:C	F56L	0.994
10:67811653:A:T	F56L	0.994
10:67811655:A:G	F56L	0.994
10:67823345:G:C	H42Q	0.993
10:67823345:G:T	H42Q	0.993
10:67811606:C:G	R72P	0.992
10:67823369:A:C	F34L	0.991
10:67823369:A:T	F34L	0.991
10:67823371:A:G	F34L	0.991
10:67811645:A:G	L59P	0.990
10:67811637:C:G	A62P	0.986
10:67823347:G:T	H42N	0.985
10:67797134:G:C	F193L	0.984
10:67797134:G:T	F193L	0.984
10:67797136:A:G	F193L	0.984
10:67811624:A:G	L66P	0.984
10:67823358:G:T	A38D	0.982
10:67811585:C:G	R79P	0.981
10:67837949:A:C	C21W	0.981
10:67837951:A:G	C21R	0.980
10:67811598:A:C	Y75D	0.979
10:67811624:A:T	L66Q	0.979
10:67823346:T:C	H42R	0.978
10:67823359:C:G	A38P	0.978
10:67837950:C:T	C21Y	0.978
10:67811654:A:G	F56S	0.973
10:67823377:C:G	A32P	0.970
10:67805778:A:G	W103R	0.969
10:67805778:A:T	W103R	0.969

dbSNP variants (sampled 300 via entrez): RS1000174330 (10:67809794 A>C), RS1000305839 (10:67822523 G>A,C), RS1000313748 (10:67812535 C>T), RS1000348567 (10:67815908 C>T), RS1000413563 (10:67825629 T>C), RS1000422106 (10:67815641 G>A), RS1000569621 (10:67801137 T>C), RS1000644587 (10:67797843 A>C,T), RS1000680071 (10:67807466 T>A), RS1000691853 (10:67809572 G>A), RS1000767522 (10:67803077 C>A,T), RS1000818694 (10:67803322 C>T), RS1000914077 (10:67821006 C>T), RS1000926231 (10:67827657 G>A,C), RS1000987694 (10:67825387 G>C)

Disease associations

OMIM: gene MIM:606060 | disease phenotypes: MIM:617384

GenCC curated gene-disease

Disease	Classification	Inheritance
hyperphenylalaninemia due to DNAJC12 deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hyperphenylalaninemia due to DNAJC12 deficiency	Definitive	AR

Mondo (1): hyperphenylalaninemia due to DNAJC12 deficiency (MONDO:0044304)

Orphanet (1): Hyperphenylalaninemia due to DNAJC12 deficiency (Orphanet:508523)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000639	Nystagmus
HP:0000750	Delayed speech and language development
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001290	Generalized hypotonia
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0002067	Bradykinesia
HP:0002136	Broad-based gait
HP:0002509	Limb hypertonia
HP:0007018	Attention deficit hyperactivity disorder
HP:0008936	Axial hypotonia
HP:0010553	Oculogyric crisis

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST007576_105	Chronotype	3.000000e-09
GCST90002395_24	Mean platelet volume	7.000000e-09
GCST90002398_175	Neutrophil count	8.000000e-14
GCST90002407_97	White blood cell count	5.000000e-13
GCST90013406_34	Liver enzyme levels (alkaline phosphatase)	8.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0004833	neutrophil count
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
Cyclosporine	increases expression, affects cotreatment	5
methylmercuric chloride	decreases expression	3
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression	3
Tretinoin	decreases expression, increases expression	3
Vorinostat	affects cotreatment, increases expression	2
Estradiol	increases expression, increases reaction, affects cotreatment, decreases expression	2
Cadmium Chloride	decreases expression	2
tungsten carbide	affects cotreatment, decreases expression	1
beta-lapachone	increases expression	1
afimoxifene	decreases expression	1
sodium arsenite	affects methylation	1
3,4,3’,4’-tetrachlorobiphenyl	affects expression	1
beta-methylcholine	affects expression	1
nefazodone	affects cotreatment, increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
torcetrapib	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
(+)-JQ1 compound	decreases expression	1
Atazanavir Sulfate	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Decitabine	decreases expression	1
Troglitazone	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_UM03	DHMCi003-A	Induced pluripotent stem cell	Male
CVCL_UM04	DHMCi003-B	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.