DNAJC13

Summary

DNAJC13 (DnaJ heat shock protein family (Hsp40) member C13, HGNC:30343) is a protein-coding gene on chromosome 3q22.1, encoding DnaJ homolog subfamily C member 13 (O75165). Involved in membrane trafficking through early endosomes, such as the early endosome to recycling endosome transport implicated in the recycling of transferrin and the early endosome to late endosome transport implicated in degradation of EGF and EGFR. It is a selective cancer dependency (DepMap: 13.0% of cell lines).

This gene encodes a member of the Dnaj protein family whose members act as co-chaperones of a partner heat-shock protein by binding to the latter and stimulating ATP hydrolysis. The encoded protein associates with the heat-shock protein Hsc70 and plays a role in clathrin-mediated endocytosis. It may also be involved in post-endocytic transport mechanisms via its associations with other proteins, including the sorting nexin SNX1. Mutations in this gene are associated with Parkinson’s disease.

Source: NCBI Gene 23317 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary late onset Parkinson disease (Supportive, GenCC)
• GWAS associations: 31
• Clinical variants (ClinVar): 473 total
• Phenotypes (HPO): 34
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 13.0% of screened cell lines
• MANE Select transcript: NM_015268

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30343
Approved symbol	DNAJC13
Name	DnaJ heat shock protein family (Hsp40) member C13
Location	3q22.1
Locus type	gene with protein product
Status	Approved
Aliases	RME8, KIAA0678
Ensembl gene	ENSG00000138246
Ensembl biotype	protein_coding
OMIM	614334
Entrez	23317

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 3 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000260818, ENST00000463038, ENST00000464766, ENST00000471925, ENST00000486798, ENST00000506813, ENST00000509279, ENST00000513822, ENST00000650455

RefSeq mRNA: 2 — MANE Select: NM_015268 NM_001329126, NM_015268

CCDS: CCDS33857

Canonical transcript exons

ENST00000260818 — 56 exons

Exon	Start	End
ENSE00000933898	132496528	132496663
ENSE00000933899	132499126	132499310
ENSE00000933900	132499734	132499808
ENSE00000933901	132500794	132500913
ENSE00000933902	132502289	132502468
ENSE00000933903	132503214	132503381
ENSE00000933904	132505302	132505415
ENSE00000933905	132507237	132507353
ENSE00000933908	132516422	132516496
ENSE00000933909	132516704	132516816
ENSE00000933910	132522828	132522997
ENSE00000933912	132523540	132523713
ENSE00000933913	132525610	132525789
ENSE00000933914	132526141	132526281
ENSE00000933915	132528189	132528332
ENSE00000933916	132530998	132531097
ENSE00001078094	132514571	132514670
ENSE00001078099	132538176	132539032
ENSE00001078100	132511067	132511244
ENSE00001078101	132490897	132491051
ENSE00001372117	132488976	132489021
ENSE00001376225	132473145	132473227
ENSE00001379471	132483375	132483577
ENSE00001388031	132488298	132488452
ENSE00001390898	132482226	132482330
ENSE00001391379	132467170	132467313
ENSE00001514394	132417502	132417760
ENSE00002325288	132494144	132494259
ENSE00002362931	132492414	132492615
ENSE00002378319	132495088	132495166
ENSE00003466493	132453599	132453694
ENSE00003472549	132465995	132466070
ENSE00003479535	132480369	132480470
ENSE00003481357	132484588	132484672
ENSE00003489655	132477981	132478140
ENSE00003498192	132462467	132462523
ENSE00003500582	132466299	132466394
ENSE00003507842	132447898	132447939
ENSE00003509717	132461050	132461205
ENSE00003512376	132460250	132460357
ENSE00003524228	132474932	132475085
ENSE00003527082	132463696	132463817
ENSE00003529575	132513008	132513099
ENSE00003540048	132453298	132453504
ENSE00003554680	132454066	132454157
ENSE00003555934	132457269	132457368
ENSE00003560350	132450647	132450847
ENSE00003576768	132479227	132479289
ENSE00003598644	132456501	132456580
ENSE00003600583	132456663	132456832
ENSE00003608910	132523157	132523199
ENSE00003613837	132434538	132434618
ENSE00003639439	132456235	132456401
ENSE00003652338	132447321	132447470
ENSE00003653196	132477789	132477892
ENSE00003664252	132446475	132446550

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 93.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.7933 / max 391.4940, expressed in 1789 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38627	20.1599	1786
38629	1.9301	400
38630	0.7033	132

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	93.98	gold quality
buccal mucosa cell	CL:0002336	93.50	gold quality
saphenous vein	UBERON:0007318	93.19	gold quality
trabecular bone tissue	UBERON:0002483	93.12	gold quality
superficial temporal artery	UBERON:0001614	92.91	gold quality
parietal pleura	UBERON:0002400	92.62	gold quality
trigeminal ganglion	UBERON:0001675	92.50	gold quality
epithelium of nasopharynx	UBERON:0001951	92.48	gold quality
cauda epididymis	UBERON:0004360	92.29	gold quality
pleura	UBERON:0000977	92.17	gold quality
tibia	UBERON:0000979	92.11	gold quality
adrenal tissue	UBERON:0018303	92.06	gold quality
visceral pleura	UBERON:0002401	91.83	gold quality
stromal cell of endometrium	CL:0002255	91.78	gold quality
endometrium	UBERON:0001295	91.69	gold quality
colonic epithelium	UBERON:0000397	91.54	gold quality
germinal epithelium of ovary	UBERON:0001304	91.50	gold quality
bone marrow cell	CL:0002092	91.36	gold quality
jejunal mucosa	UBERON:0000399	91.26	gold quality
corpus epididymis	UBERON:0004359	91.22	gold quality
monocyte	CL:0000576	91.19	gold quality
jejunum	UBERON:0002115	91.19	gold quality
mononuclear cell	CL:0000842	91.16	gold quality
leukocyte	CL:0000738	90.97	gold quality
palpebral conjunctiva	UBERON:0001812	90.84	gold quality
seminal vesicle	UBERON:0000998	90.70	gold quality
myometrium	UBERON:0001296	90.67	gold quality
dorsal root ganglion	UBERON:0000044	90.64	gold quality
urethra	UBERON:0000057	90.63	gold quality
pericardium	UBERON:0002407	90.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

93 targeting DNAJC13, 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-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
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-507	99.97	70.11	1915
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-141-3P	99.94	72.79	2421

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 18)

• RME-8 functions in intracellular trafficking and provides the first evidence of a functional role for a DnaJ domain-bearing co-chaperone on endosomes (PMID:16179350)
• hRME is primarily involved in membrane trafficking through early endosomes, but not through degradative organelles, such as multivesicular bodies and late endosomes. (PMID:18256511)
• These data implicate RME-8 in sorting decisions influencing EGFR at the level of endosomes and point to RME-8 as a potential regulatory target in ErbB2-positive breast cancers. (PMID:18307993)
• Found DNAJC13 A2057S variant is probably a rare cause of Tourette syndrome/chronic tic phenotype in Chinese Han patients. (PMID:22507240)
• Missense mutations in DNAJC13 does not play a major role in PD in the Chinese population. (PMID:24126164)
• a pathogenic mutation in DNAJC13, a component of the endosomal recycling system, helps to emphasize the role of endosomal recycling rather than endolysosomal protein degradation in the biology of late-onset Parkinson disease. (PMID:24218364)
• Data propose that the interaction between RME-8 and the WASH complex provides a means to coordinate the activity of the WASH complex with the membrane-tubulating function of the sorting. (PMID:24643499)
• DNAJC13 c.2564A>G (p.(N855S)) was identified in two patients with essential tremor. (PMID:25118025)
• PD associated with a DNAJC13 p.N855S parkinsonism mutation presents as late-onset, often slowly progressive, usually dopamine-responsive typical Parkinsonism. (PMID:25186792)
• Although the contribution of rare genetic variation in DNAJC13 to parkinsonisms remains to be further elucidated, this study suggests that, in addition to p.N855S, other rare variants might affect disease susceptibility (PMID:25393719)
• Re-expression of miR-193b in breast cancer cell lines decreased DNAJC13 (HPS40) and RAB22A expression, providing a mechanism by which mir193-b acts as a tumor suppressor. (PMID:25550792)
• These results further highlight the critical role for phosphatidylinositol 3-phosphate in the RME-8-mediated organizational control of various endosomal activities, including retrograde transport. (PMID:26134565)
• Mutations in exon 24 of DNAJC13 are not a common cause of Parkinson or Lewy body disease among Caucasian populations. (PMID:26278106)
• There is a possibility that specific DNAJC13 variants may play a minor role in PD susceptibility. (PMID:27236598)
• Parkinson’s disease-linked DNAJC13 mutation perturbs multi-directional endosomal trafficking, resulting in the aberrant endosomal retention of alpha-synuclein, which might predispose to the neurodegenerative process that leads to Parkinson’s disease. (PMID:29309590)
• This study showed the DNAJC13 mutation screening in patients with Parkinson’s disease. (PMID:29887357)
• Receptor-mediated endocytosis 8 (RME-8)/DNAJC13 is a novel positive modulator of autophagy and stabilizes cellular protein homeostasis. (PMID:32322926)
• Association study of DNAJC13, UCHL1, HTRA2, GIGYF2, and EIF4G1 with Parkinson’s disease. (PMID:33239198)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dnajc13	ENSMUSG00000032560
rattus_norvegicus	Dnajc13	ENSRNOG00000011491
drosophila_melanogaster	Rme-8	FBGN0015477
caenorhabditis_elegans	rme-8	WBGENE00004378

Paralogs (20): DNAJC11 (ENSG00000007923), DNAJC25 (ENSG00000059769), DNAJC10 (ENSG00000077232), DNAJC5 (ENSG00000101152), DNAJC3 (ENSG00000102580), DNAJC17 (ENSG00000104129), DNAJC2 (ENSG00000105821), DNAJC12 (ENSG00000108176), DNAJC4 (ENSG00000110011), DNAJC16 (ENSG00000116138), DNAJC14 (ENSG00000135392), DNAJC1 (ENSG00000136770), DNAJC5B (ENSG00000147570), DNAJC5G (ENSG00000163793), DNAJC7 (ENSG00000168259), DNAJC21 (ENSG00000168724), DNAJC18 (ENSG00000170464), DNAJC24 (ENSG00000170946), DNAJC30 (ENSG00000176410), DNAJC9 (ENSG00000213551)

Protein

Protein identifiers

DnaJ homolog subfamily C member 13 — O75165 (reviewed: O75165)

Alternative names: Required for receptor-mediated endocytosis 8

All UniProt accessions (4): O75165, A0A3B3IRM0, H0Y8Q2, H0YA63

UniProt curated annotations — full annotation on UniProt →

Function. Involved in membrane trafficking through early endosomes, such as the early endosome to recycling endosome transport implicated in the recycling of transferrin and the early endosome to late endosome transport implicated in degradation of EGF and EGFR. Involved in the regulation of endosomal membrane tubulation and regulates the dynamics of SNX1 on the endosomal membrane; via association with WASHC2 may link the WASH complex to the retromer SNX-BAR subcomplex.

Subunit / interactions. Interacts with WASHC2C; mediates the association with the WASH complex.

Subcellular location. Early endosome. Early endosome membrane. Endosome membrane.

Disease relevance. Parkinson disease (PARK) [MIM:168600] A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features. The gene represented in this entry may be involved in disease pathogenesis. Genetic variants in DNAJC13 and TMEM230 have been found in the same large multigenerational family with adult-onset Parkinson disease. The pathological role of each gene and therefore the exact molecular basis of the disease is unclear.

RefSeq proteins (2): NP_001316055, NP_056083* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001623	DnaJ_domain	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR025640	GYF_2	Domain
IPR035445	GYF-like_dom_sf	Homologous_superfamily
IPR036869	J_dom_sf	Homologous_superfamily
IPR044978	GRV2/DNAJC13	Family
IPR045802	GRV2/DNAJC13_N	Domain

Pfam: PF00226, PF14237, PF19432

UniProt features (34 total): sequence variant 21, sequence conflict 9, chain 1, domain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75165-F1	82.91	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 (1): 84

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 265 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ENDOSOME_ORGANIZATION, GOCC_VACUOLAR_MEMBRANE, PAL_PRMT5_TARGETS_UP, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, ONKEN_UVEAL_MELANOMA_UP, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_REGULATION_OF_EARLY_ENDOSOME_TO_LATE_ENDOSOME_TRANSPORT, MODULE_206

GO Biological Process (6): osteoblast differentiation (GO:0001649), receptor-mediated endocytosis (GO:0006898), endosome organization (GO:0007032), protein transport (GO:0015031), obsolete regulation of early endosome to recycling endosome transport (GO:1902954), regulation of early endosome to late endosome transport (GO:2000641)

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

GO Cellular Component (12): lysosomal membrane (GO:0005765), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), membrane (GO:0016020), secretory granule membrane (GO:0030667), early endosome membrane (GO:0031901), azurophil granule membrane (GO:0035577), extracellular exosome (GO:0070062), endosome (GO:0005768), early endosome (GO:0005769), WASH complex (GO:0071203)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
endosome	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
ossification	1
cell differentiation	1
endocytosis	1
endomembrane system organization	1
vesicle organization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
regulation of intracellular transport	1
early endosome to late endosome transport	1
regulation of vesicle-mediated transport	1
binding	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
secretory granule	1
early endosome	1
endosome membrane	1
lysosomal membrane	1
secretory granule membrane	1
azurophil granule	1
extracellular vesicle	1
endomembrane system	1
cytoplasmic vesicle	1
protein-containing complex	1

Protein interactions and networks

STRING

1366 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJC13	SNX1	Q13596	917
DNAJC13	VPS35	Q96QK1	904
DNAJC13	DNAJC6	O75061	811
DNAJC13	TMEM230	Q96A57	731
DNAJC13	ATP13A2	Q9NQ11	731
DNAJC13	SYNJ1	O43426	728
DNAJC13	HSPA8	P11142	716
DNAJC13	VPS13C	Q709C8	691
DNAJC13	VPS29	Q9UBQ0	691
DNAJC13	CHCHD2	Q9Y6H1	690
DNAJC13	VPS26A	O75436	670
DNAJC13	EIF4G1	Q04637	669
DNAJC13	DNAJB2	P25686	664
DNAJC13	PLA2G6	O60733	663
DNAJC13	FBXO7	Q9Y3I1	660

IntAct

151 interactions, top by confidence:

A	B	Type	Score
HSPA8	GAK	psi-mi:“MI:0914”(association)	0.760
LRIF1	SMCHD1	psi-mi:“MI:0914”(association)	0.680
TMEM9B	DNAJC13	psi-mi:“MI:0914”(association)	0.640
SCAMP1	DNAJC13	psi-mi:“MI:0915”(physical association)	0.620
SCAMP1	DNAJC13	psi-mi:“MI:0914”(association)	0.620
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
NEURL4	APBB1	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
FCN1	POTEF	psi-mi:“MI:0914”(association)	0.530
LGALS3BP	RGPD8	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
LIPG	NRP1	psi-mi:“MI:0914”(association)	0.530
OCLN	DNAJC13	psi-mi:“MI:0914”(association)	0.530
SLC39A9	B4GALT5	psi-mi:“MI:0914”(association)	0.530
BAG4	DNAJC13	psi-mi:“MI:0914”(association)	0.530
HSPA9	DNAJC13	psi-mi:“MI:0914”(association)	0.530
JPH4	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
STUB1	DNAJC13	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530

BioGRID (207): DNAJC13 (Affinity Capture-MS), DNAJC13 (Affinity Capture-MS), DNAJC13 (Affinity Capture-MS), DNAJC13 (Affinity Capture-MS), AP1G1 (Co-fractionation), ATP6V1A (Co-fractionation), DNAJC13 (Co-fractionation), PRMT7 (Co-fractionation), DNAJC13 (Affinity Capture-MS), DNAJC13 (Biochemical Activity), DNAJC13 (Affinity Capture-MS), DNAJC13 (Affinity Capture-MS), DNAJC13 (Affinity Capture-MS), DNAJC13 (Affinity Capture-MS), DNAJC13 (Affinity Capture-MS)

ESM2 similar proteins: A2AU72, B0F9L4, E9Q912, F1QWA8, O35099, O46563, O75165, O75602, O93614, P0C6R2, P39968, P42345, P42346, P52306, Q04173, Q1RMS6, Q21029, Q5EFZ4, Q5PPZ9, Q5W041, Q5ZL91, Q66L58, Q68FK4, Q6BTZ4, Q6C5Y8, Q6CX49, Q6DD21, Q6FJV1, Q6NUP7, Q6PIY5, Q757R0, Q7YRF1, Q80TR8, Q80W92, Q80WQ2, Q84ZC0, Q8BVE3, Q8BW49, Q8C0Y0, Q8NFP9

Diamond homologs: A0Q1R3, A1BHL1, A1K4C4, A1S8K6, A1U613, A3N3J9, A4G8D1, A4SFR5, A4XKA5, A4XYF5, A5N6M3, A5UF67, A5W9A2, A5WBF8, A6VCL7, A6VNB0, A8EUC7, A9KG87, B0BTI6, B0JW23, B0KIS4, B0UWR3, B1J255, B1ZUS0, B2J3J3, B2TLZ8, B2UBP2, B2V2I6, B3EE31, B3PXH2, B3QPW8, B6IZJ1, B6J7U6, B7V1H2, B8CXL0, B8F7S3, B9FHF3, B9MJZ0, C1DFM2, C3K274

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 170 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of HSF1-mediated heat shock response	8	9.9×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	11	7.6×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	233
Likely benign	40
Benign	129

Top pathogenic / likely-pathogenic (0)

SpliceAI

7719 predictions. Top by Δscore:

Variant	Effect	Δscore
3:132417756:CGAAG:C	donor_loss	1.0000
3:132417759:AGGTA:A	donor_loss	1.0000
3:132417760:GGTA:G	donor_loss	1.0000
3:132434614:GGGAA:G	donor_gain	1.0000
3:132434615:GGAA:G	donor_gain	1.0000
3:132434615:GGAAG:G	donor_gain	1.0000
3:132434616:GAA:G	donor_gain	1.0000
3:132434616:GAAG:G	donor_gain	1.0000
3:132434619:G:GG	donor_gain	1.0000
3:132447318:A:AG	acceptor_gain	1.0000
3:132447318:AAGT:A	acceptor_gain	1.0000
3:132447318:AAGTG:A	acceptor_gain	1.0000
3:132447319:A:G	acceptor_gain	1.0000
3:132447319:AGT:A	acceptor_gain	1.0000
3:132447320:G:GG	acceptor_gain	1.0000
3:132447320:GT:G	acceptor_gain	1.0000
3:132447320:GTG:G	acceptor_gain	1.0000
3:132447468:TTGGT:T	donor_loss	1.0000
3:132447469:TGGTA:T	donor_loss	1.0000
3:132447470:GGTAA:G	donor_loss	1.0000
3:132447471:G:GG	donor_gain	1.0000
3:132447471:G:T	donor_loss	1.0000
3:132447472:T:A	donor_loss	1.0000
3:132447935:G:GT	donor_gain	1.0000
3:132447938:GG:G	donor_gain	1.0000
3:132447939:GG:G	donor_gain	1.0000
3:132450643:TTA:T	acceptor_loss	1.0000
3:132450644:TA:T	acceptor_loss	1.0000
3:132450645:A:AG	acceptor_gain	1.0000
3:132450645:A:T	acceptor_loss	1.0000

AlphaMissense

14827 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:132434599:A:C	K17Q	1.000
3:132434599:A:G	K17E	1.000
3:132434600:A:T	K17I	1.000
3:132434601:A:C	K17N	1.000
3:132434601:A:T	K17N	1.000
3:132434608:T:A	W20R	1.000
3:132434608:T:C	W20R	1.000
3:132434610:G:C	W20C	1.000
3:132434610:G:T	W20C	1.000
3:132434612:G:C	R21T	1.000
3:132434613:G:C	R21S	1.000
3:132434613:G:T	R21S	1.000
3:132434614:G:A	G22R	1.000
3:132434614:G:C	G22R	1.000
3:132434615:G:A	G22E	1.000
3:132446476:T:C	Y24H	1.000
3:132446482:C:A	R26S	1.000
3:132447321:T:A	W49R	1.000
3:132447321:T:C	W49R	1.000
3:132447323:G:C	W49C	1.000
3:132447323:G:T	W49C	1.000
3:132447430:T:C	F85S	1.000
3:132453353:C:A	A198D	1.000
3:132453648:G:C	R265P	1.000
3:132456805:G:A	G441D	1.000
3:132461146:T:C	F552L	1.000
3:132461148:T:A	F552L	1.000
3:132461148:T:G	F552L	1.000
3:132466023:T:A	W641R	1.000
3:132466023:T:C	W641R	1.000

dbSNP variants (sampled 300 via entrez): RS1000012415 (3:132417438 G>A), RS1000044824 (3:132508441 A>G), RS1000079643 (3:132431925 C>A,T), RS1000095951 (3:132460900 A>C), RS1000098565 (3:132478070 T>C), RS1000112756 (3:132498203 A>G), RS1000171281 (3:132487302 G>A), RS1000211182 (3:132506679 G>A), RS1000217202 (3:132441582 G>A), RS1000240678 (3:132506845 C>T), RS1000250011 (3:132538949 A>G), RS1000267537 (3:132434450 A>C,G), RS1000324842 (3:132498981 G>A), RS1000329546 (3:132451906 G>T), RS1000352392 (3:132493913 G>T)

Disease associations

OMIM: gene MIM:614334 | disease phenotypes: MIM:168600, MIM:190300, MIM:616361

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary late onset Parkinson disease	Supportive	Autosomal dominant

Mondo (5): vascular dementia (MONDO:0004648), late-onset Parkinson disease (MONDO:0008199), essential tremor (MONDO:0003233), Parkinson disease 21 (MONDO:0014604), (MONDO:0018466)

Orphanet (2): Hereditary late-onset Parkinson disease (Orphanet:411602), NON RARE IN EUROPE: Hereditary essential tremor (Orphanet:862)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000338	Hypomimic face
HP:0000651	Diplopia
HP:0000713	Agitation
HP:0000716	Depression
HP:0000726	Dementia
HP:0000741	Apathy
HP:0000744	Low frustration tolerance
HP:0001268	Mental deterioration
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002120	Cerebral cortical atrophy
HP:0002171	Gliosis
HP:0002172	Postural instability
HP:0002304	Akinesia
HP:0002322	Resting tremor
HP:0002359	Frequent falls
HP:0002360	Sleep disturbance
HP:0002362	Shuffling gait
HP:0002367	Visual hallucination
HP:0002548	Parkinsonism with favorable response to dopaminergic medication
HP:0003394	Muscle spasm
HP:0004409	Hyposmia
HP:0004926	Orthostatic hypotension due to autonomic dysfunction
HP:0005340	Spastic/hyperactive bladder
HP:0012450	Chronic constipation
HP:0031435	Monotonic speech

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST004571_20	Iron status biomarkers (total iron binding capacity)	8.000000e-07
GCST004572_1	Iron status biomarkers (transferrin saturation)	8.000000e-07
GCST004621_133	Red cell distribution width	1.000000e-10
GCST005195_61	Coronary artery disease	3.000000e-09
GCST005196_109	Coronary artery disease	2.000000e-08
GCST005951_142	Body mass index	1.000000e-09
GCST006612_38	LDL cholesterol	2.000000e-10
GCST006614_45	Total cholesterol levels	2.000000e-10
GCST006804_143	Red cell distribution width	3.000000e-10
GCST008971_23	Urate levels	2.000000e-09
GCST008972_68	Urate levels	1.000000e-09
GCST010002_440	Refractive error	5.000000e-09
GCST010083_83	Hemoglobin levels	1.000000e-10
GCST010204_82	Low density lipoprotein cholesterol levels	8.000000e-20
GCST010243_33	Apolipoprotein B levels	9.000000e-19
GCST010245_154	LDL cholesterol levels	1.000000e-18
GCST010699_54	Brain morphology (min-P)	5.000000e-08
GCST010701_80	Cortical surface area (MOSTest)	5.000000e-09
GCST010702_60	Subcortical volume (MOSTest)	6.000000e-12
GCST010703_12	Brain morphology (MOSTest)	9.000000e-10
GCST90000025_950	Appendicular lean mass	8.000000e-20
GCST90002383_373	Hematocrit	5.000000e-09
GCST90002384_214	Hemoglobin	2.000000e-11
GCST90002390_160	Mean corpuscular hemoglobin	2.000000e-33
GCST90002391_3	Mean corpuscular hemoglobin concentration	4.000000e-14
GCST90002392_307	Mean corpuscular volume	2.000000e-27
GCST90002398_430	Neutrophil count	6.000000e-11
GCST90002404_53	Red cell distribution width	1.000000e-33
GCST90002407_409	White blood cell count	2.000000e-10
GCST90011899_124	Aspartate aminotransferase levels	3.000000e-13

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0006334	total iron binding capacity
EFO:0009188	Red cell distribution width
EFO:0004340	body mass index
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004531	urate measurement
EFO:0004509	hemoglobin measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass
EFO:0004348	hematocrit
EFO:0004527	mean corpuscular hemoglobin
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004833	neutrophil count
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D015140	Dementia, Vascular	C10.228.140.300.400; C10.228.140.300.510.800.500; C10.228.140.380.230; C10.228.140.695.500; C14.907.137.126.372.500; C14.907.253.560.350.500; F03.615.400.350
D020329	Essential Tremor	C10.228.662.350

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067017 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
bisphenol F	increases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
salinomycin	decreases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases abundance, decreases expression	1
tetrabromobisphenol A	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
torcetrapib	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Air Pollutants	increases abundance, increases oxidation, affects cotreatment	1
Arsenic	decreases expression, increases abundance	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652895	Binding	Binding affinity to human DNAJC13 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1Q9	Abcam HeLa DNAJC13 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00165763	PHASE4	COMPLETED	Efficacy and Safety of Donepezil Hydrochloride (Aricept) in Vascular Dementia
NCT00847860	PHASE4	COMPLETED	Cilostazol Verse Asprin for Vascular Dementia in Poststroke Patients With White Matter Lesions
NCT00947531	PHASE4	COMPLETED	A Clinical Trial to Evaluate the Safety and Efficacy of 20 ml Cerebrolysin in Patients With Vascular Dementia
NCT00950430	PHASE4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT00455143	PHASE4	TERMINATED	Cognitive Protection - Dexmedetomidine and Cognitive Reserve
NCT00561678	PHASE4	COMPLETED	Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve
NCT01807481	PHASE4	UNKNOWN	Phase IV Study to Evaluate the Efficacy and Safety of Mircera in PD
NCT00439699	PHASE4	COMPLETED	A Pilot Clinical Trial Of Memantine for Essential Tremor
NCT00584376	PHASE4	COMPLETED	Pregabalin (Lyrica) for the Treatment of Essential Tremor
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02111369	PHASE4	COMPLETED	Propranolol and Botulinum Toxin for Essential Vocal Tremor
NCT02495883	PHASE4	COMPLETED	Functional Imaging of Tremor Circuits and Mechanisms of Treatment Response
NCT00099216	PHASE3	COMPLETED	Efficacy and Safety of Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00130338	PHASE3	COMPLETED	Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00209456	PHASE3	COMPLETED	Dopamine Transporter Scintigraphy Imaging (DAT-Imaging) in Patients With Lewy Body Dementia
NCT00249158	PHASE3	COMPLETED	A Study of the Effectiveness and Safety of Risperidone in the Treatment of Behavioral Disturbances in Patients With Dementia
NCT00261573	PHASE3	COMPLETED	A Study of the Safety and Effectiveness of Galantamine Versus Placebo in the Treatment of Patients With Vascular Dementia or Mixed Dementia
NCT00621647	PHASE3	COMPLETED	Seroquel- Agitation Associated With Dementia
NCT02453932	PHASE3	COMPLETED	Efficacy and Safety of Tianzhi Granule in Mild to Moderate Vascular Dementia
NCT03682185	PHASE3	COMPLETED	The Healthy Patterns Sleep Study
NCT03789760	PHASE3	COMPLETED	The Clinical Trial of Chinese Herbal Medicine (SaiLuoTong) Capsule
NCT03804229	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Butylphthalide Soft Capsule for the Treatment of Vascular Dementia
NCT03986424	PHASE3	COMPLETED	Local Study of Akatinol Memantine in VaD in Russia
NCT04552041	PHASE3	COMPLETED	Prospekta in the Treatment of Cognitive, Behavioral and Psychiatric Disorders in Patients With Vascular Dementia.
NCT07015671	PHASE3	COMPLETED	Bioavailability and Bioequivalence Study of ER Torsemide and Spironolactone FDC Tablet in Healthy Subjects
NCT00018564	PHASE3	COMPLETED	Novel Therapies for Essential Tremor
NCT00236496	PHASE3	COMPLETED	A Comparison of the Efficacy and Safety of Topiramate Versus Placebo in Treating Tremor of Unknown Cause.
NCT01441284	PHASE3	WITHDRAWN	Efficacy of Pramipexole Extended Release in the Treatment of Essential Tremor
NCT04193527	PHASE3	COMPLETED	A Study to Evaluate the Diagnostic Efficacy of DaTSCAN™ Ioflupane (123I) Injection in Single Photon Emission Computed Tomography (SPECT) for the Diagnosis of Parkinsonian Syndrome (PS) in Chinese Patients
NCT04265209	PHASE3	COMPLETED	[18F] LBT-999 PET Compared to [123I]-FP/CIT SPECT to Distinguish Between Parkinson’s Diseases and Essential Tremor
NCT06087276	PHASE3	ENROLLING_BY_INVITATION	Essential 3 - Decentralized, Phase 3 Study Evaluating the Safety and Efficacy of Ulixacaltamide in Essential Tremor (ET)
NCT01466543	PHASE2	UNKNOWN	Effect of Zydena (Udenafil) on Cerebral Blood Flow and Peripheral Blood Viscosity
NCT01475578	PHASE2	COMPLETED	Study of STA-1 Capsule in Patients With Vascular Dementia (Marrow-Sea Deficiency)
NCT01608217	PHASE2	COMPLETED	Delta-THC in Dementia
NCT01761227	PHASE2	COMPLETED	Efficacy and Safety of Fufangdanshen Tablets in Mild to Moderate Vascular Dementia
NCT01953705	PHASE2	UNKNOWN	n-3 PUFA for Vascular Cognitive Aging
NCT01965756	PHASE2	COMPLETED	Effect of Insulin Sensitizer Metformin on AD Biomarkers
NCT01978730	PHASE2	UNKNOWN	The Clinical Trial of Chinese Herbal Medicine SaiLuoTong Capsule
NCT02467413	PHASE2	WITHDRAWN	BAC in Patient With Alzheimer’s Disease or Vascular Dementia
NCT03230071	PHASE2	COMPLETED	Efficacy and Safety of TMBCZG in Mild to Moderate Vascular Dementia