DNAJC7

Summary

DNAJC7 (DnaJ heat shock protein family (Hsp40) member C7, HGNC:12392) is a protein-coding gene on chromosome 17q21.2, encoding DnaJ homolog subfamily C member 7 (Q99615). Acts as a co-chaperone regulating the molecular chaperones HSP70 and HSP90 in folding of steroid receptors, such as the glucocorticoid receptor and the progesterone receptor.

This gene encodes a member of the DNAJ heat shock protein 40 family of proteins that is characterized by two N-terminal tetratricopeptide repeat domains and a C-terminal DNAJ domain. This protein binds the chaperone proteins heat shock proteins 70 and 90 in an ATP-dependent manner and may function as a co-chaperone. Pseudogenes of this gene are found on chromosomes 1 and 6. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 7266 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis (Limited, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 54 total
• Phenotypes (HPO): 1
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003315

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12392
Approved symbol	DNAJC7
Name	DnaJ heat shock protein family (Hsp40) member C7
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	TPR2
Ensembl gene	ENSG00000168259
Ensembl biotype	protein_coding
OMIM	601964
Entrez	7266

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 26 protein_coding, 10 nonsense_mediated_decay, 8 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000316603, ENST00000426588, ENST00000457167, ENST00000585693, ENST00000585866, ENST00000586240, ENST00000586335, ENST00000587727, ENST00000588641, ENST00000588814, ENST00000589547, ENST00000589576, ENST00000589586, ENST00000589773, ENST00000589810, ENST00000590197, ENST00000590348, ENST00000590774, ENST00000590847, ENST00000590886, ENST00000591153, ENST00000591787, ENST00000674166, ENST00000674175, ENST00000674179, ENST00000674214, ENST00000674233, ENST00000674249, ENST00000674252, ENST00000674287, ENST00000674303, ENST00000674306, ENST00000674337, ENST00000674355, ENST00000674411, ENST00000674425, ENST00000674453, ENST00000674472, ENST00000674481, ENST00000674485, ENST00000674497, ENST00000674504, ENST00000904029, ENST00000904030, ENST00000904031, ENST00000968335

RefSeq mRNA: 2 — MANE Select: NM_003315 NM_001144766, NM_003315

CCDS: CCDS45677, CCDS45678

Canonical transcript exons

ENST00000457167 — 14 exons

Exon	Start	End
ENSE00002364286	41976435	41976770
ENSE00002372208	42017340	42017439
ENSE00003489929	41981855	41982007
ENSE00003496889	41983563	41983636
ENSE00003506690	41989404	41989557
ENSE00003538130	41982255	41982401
ENSE00003539040	41987819	41987910
ENSE00003575004	41977261	41977323
ENSE00003594999	41997115	41997239
ENSE00003609170	41990264	41990382
ENSE00003667977	41988732	41988896
ENSE00003677827	41996311	41996424
ENSE00003687181	42000482	42000570
ENSE00003790808	41994870	41994944

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 97.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 63.9863 / max 1363.5934, expressed in 1825 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166078	49.1083	1824
166073	4.1146	1188
166076	2.9323	1062
166077	2.3272	1145
166083	1.8873	463
166079	1.1840	844
166082	0.9958	633
166081	0.6560	394
166075	0.5087	163
166080	0.2722	91

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	97.50	gold quality
lower esophagus mucosa	UBERON:0035834	97.34	gold quality
caudate nucleus	UBERON:0001873	97.28	gold quality
right frontal lobe	UBERON:0002810	97.18	gold quality
monocyte	CL:0000576	97.01	gold quality
adenohypophysis	UBERON:0002196	97.01	gold quality
mucosa of transverse colon	UBERON:0004991	97.00	gold quality
apex of heart	UBERON:0002098	96.95	gold quality
cingulate cortex	UBERON:0003027	96.82	gold quality
anterior cingulate cortex	UBERON:0009835	96.78	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.78	gold quality
gastrocnemius	UBERON:0001388	96.76	gold quality
mononuclear cell	CL:0000842	96.74	gold quality
ganglionic eminence	UBERON:0004023	96.72	gold quality
leukocyte	CL:0000738	96.69	gold quality
putamen	UBERON:0001874	96.68	gold quality
cortical plate	UBERON:0005343	96.65	gold quality
amygdala	UBERON:0001876	96.58	gold quality
cerebellar hemisphere	UBERON:0002245	96.58	gold quality
muscle of leg	UBERON:0001383	96.55	gold quality
cerebellar cortex	UBERON:0002129	96.55	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.53	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.51	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.50	gold quality
prefrontal cortex	UBERON:0000451	96.42	gold quality
pituitary gland	UBERON:0000007	96.37	gold quality
islet of Langerhans	UBERON:0000006	96.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.21	gold quality
ventricular zone	UBERON:0003053	96.16	gold quality
calcaneal tendon	UBERON:0003701	95.97	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.67
E-MTAB-9801	yes	4.24

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

35 targeting DNAJC7, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-513B-5P	99.99	69.96	2150
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-3692-3P	99.98	70.27	2139
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-6864-5P	98.38	66.59	1079
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-4286	97.20	64.37	1587

Literature-anchored findings (GeneRIF, showing 12)

• TPR2 combines two TPR domains and a J domain to regulate the Hsp70/Hsp90 chaperone system. (PMID:12853476)
• Data show that Tpr2 associates with Hsp90 and Hsp70 complexes, promoted the accumulation of Hsp70 in PR heterocomplexes in the presence of Hsp90. Thus, Tpr2 has the potential to regulate PR chaperoning. (PMID:18620420)
• TPR2 exhibited strong interaction with glucocorticoid receptor and progesterone receptors. (PMID:20661446)
• these findings strongly suggest that DnaJC7 participates in p53/MDM2 negative feedback regulatory pathway, and thereby enhancing the stability and activity of p53. (PMID:23261415)
• ubiquitin-proteasomal regulation of CCRP and HSP70 are important contributors to the regulation of cytoplasmic CAR levels, and hence the ability of CAR to respond to PB or PB-like inducers (PMID:24789201)
• The data from the current study for the first time demonstrated increased serum polyglutamylated DNAJC7 as a potential biomarker for renal cell carcinoma early detection (PMID:26993597)
• results highlight DNAJC7 as a novel gene for ALS. (PMID:31768050)
• Mutations of DNAJC7 are rare in Chinese amyotrophic lateral sclerosis patients. (PMID:32897108)
• Validation of the pathogenic role of rare DNAJC7 variants in Chinese patients with amyotrophic lateral sclerosis. (PMID:34233860)
• Mutation screening of the DNAJC7 gene in Japanese patients with sporadic amyotrophic lateral sclerosis. (PMID:35039179)
• DnaJC7 in Amyotrophic Lateral Sclerosis. (PMID:35456894)
• Rare DNAJC7 Variants May Play a Minor Role in Chinese Patients with ALS. (PMID:37870677)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajc7	ENSDARG00000058148
mus_musculus	Dnajc7	ENSMUSG00000014195
rattus_norvegicus	Dnajc7	ENSRNOG00000017781
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	dnj-28	WBGENE00001046
caenorhabditis_elegans		WBGENE00008122

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), DNAJC13 (ENSG00000138246), DNAJC5B (ENSG00000147570), DNAJC5G (ENSG00000163793), DNAJC21 (ENSG00000168724), DNAJC18 (ENSG00000170464), DNAJC24 (ENSG00000170946), DNAJC30 (ENSG00000176410), DNAJC9 (ENSG00000213551)

Protein

Protein identifiers

DnaJ homolog subfamily C member 7 — Q99615 (reviewed: Q99615)

Alternative names: Tetratricopeptide repeat protein 2

All UniProt accessions (23): A0A6I8PIK4, A0A6I8PLE7, A0A6I8PR89, A0A6I8PR93, A0A6I8PRZ0, A0A6I8PS32, A0A6I8PU73, A0A6I8PU89, A0A6I8PUC2, A0A6I8PUD4, Q99615, K7EIH8, K7EJE9, K7EJL5, K7EJV7, K7EK03, K7ELJ8, K7EN19, K7ENB7, K7EPP7, K7EQ73, K7ER44, K7ESP1

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a co-chaperone regulating the molecular chaperones HSP70 and HSP90 in folding of steroid receptors, such as the glucocorticoid receptor and the progesterone receptor. Proposed to act as a recycling chaperone by facilitating the return of chaperone substrates to early stages of chaperoning if further folding is required. In vitro, induces ATP-independent dissociation of HSP90 but not of HSP70 from the chaperone-substrate complexes. Recruits NR1I3 to the cytoplasm.

Subunit / interactions. Associates with complexes containing chaperones HSP70 and HSP90. Interacts with the GAP domain of NF1. Interacts with HSP90AA1. Interacts with HSPA1A/B; the interaction is enhanced by ATP. Interacts with HSP90AB1. Interacts with PGR. Interacts with RAD9A; the interaction is interrupted by UV and heat shock treatments. Interacts with HUS1 and RAD1. Interacts with NR1I3. The DNAJC7-NR1I3 complex may also include HSP90. Interacts with HSPA8.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99615-1	1	yes
Q99615-2	2

RefSeq proteins (2): NP_001138238, NP_003306* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001623	DnaJ_domain	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR036869	J_dom_sf	Homologous_superfamily

Pfam: PF00226, PF13181, PF13414, PF13432

UniProt features (19 total): repeat 9, mutagenesis site 3, modified residue 2, initiator methionine 1, chain 1, domain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99615-F1	90.83	0.82

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 (2): 2, 393

Mutagenesis-validated functional residues (3):

Position	Phenotype
101	impairs interaction with hsp90aa1 and hspa1a/b. abolishes interaction with hsp90aa1 and hspa1a/b; when associated with a
333	impairs interaction with hsp90aa1 and hspa1a/b. abolishes interaction with hsp90aa1 and hspa1a/b; when associated with a
409	predominantly nuclear localization. abolishes interaction with hsp90aa1 and hspa1a/b; when associated with a-101 and a-3

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3371453	Regulation of HSF1-mediated heat shock response

MSigDB gene sets: 199 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, SP3_Q3, AP2_Q3, GGGTGGRR_PAX4_03, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_HEAT, GOBP_PROTEIN_MATURATION, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, WANG_LMO4_TARGETS_DN, MORF_FANCG, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_PROTEIN_FOLDING, GARY_CD5_TARGETS_DN, GOBP_CELLULAR_RESPONSE_TO_HEAT, CCCNNNNNNAAGWT_UNKNOWN, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS

GO Biological Process (2): protein folding (GO:0006457), regulation of cellular response to heat (GO:1900034)

GO Molecular Function (3): ATPase activator activity (GO:0001671), heat shock protein binding (GO:0031072), protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), membrane (GO:0016020), extracellular exosome (GO:0070062), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cellular response to heat stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular process	1
protein maturation	1
cellular response to heat	1
regulation of cellular response to stress	1
ATP-dependent activity	1
molecular function activator activity	1
protein binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1
extracellular vesicle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3243 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJC7	HSP90AA1	P07900	824
DNAJC7	HSP90AB1	P08238	818
DNAJC7	HSPA4	P34932	814
DNAJC7	CNP	P09543	765
DNAJC7	TTC1	Q99614	683
DNAJC7	TTC9C	Q8N5M4	663
DNAJC7	WRAP73	Q9P2S5	547
DNAJC7	PEX5	P50542	533
DNAJC7	AHSA1	O95433	488
DNAJC7	BAG2	O95816	487
DNAJC7	FKBP4	Q02790	481
DNAJC7	GLT8D1	Q68CQ7	465
DNAJC7	GRPEL1	Q9HAV7	456
DNAJC7	HSP90B1	P14625	452
DNAJC7	TCP1	P17987	442

IntAct

200 interactions, top by confidence:

A	B	Type	Score
TP53	MDM4	psi-mi:“MI:0914”(association)	0.970
IFT122	WDR19	psi-mi:“MI:0914”(association)	0.800
DNAJC7	BAG2	psi-mi:“MI:0915”(physical association)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
TP53	BAG2	psi-mi:“MI:0914”(association)	0.640
BAG4	DNAJC7	psi-mi:“MI:0915”(physical association)	0.620
PWP2	FBL	psi-mi:“MI:0914”(association)	0.610
Sh2d5	BCR	psi-mi:“MI:0914”(association)	0.580
vif	DNAJC7	psi-mi:“MI:0915”(physical association)	0.560
MLF2	DNAJC7	psi-mi:“MI:0915”(physical association)	0.560
DNAJC7	HSPA1L	psi-mi:“MI:0915”(physical association)	0.560
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
NEURL4	APBB1	psi-mi:“MI:0914”(association)	0.530
IFT122	DNAJA2	psi-mi:“MI:0914”(association)	0.530
EEF1G	INPPL1	psi-mi:“MI:0914”(association)	0.530
ABHD15	HSPA8	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
KLHL10	PXDNL	psi-mi:“MI:0914”(association)	0.530
MID1IP1	ACACB	psi-mi:“MI:0914”(association)	0.530
TAF1C	DNAJA2	psi-mi:“MI:0914”(association)	0.530
rep	NKRF	psi-mi:“MI:0914”(association)	0.500
vif	UBL4A	psi-mi:“MI:0914”(association)	0.500

BioGRID (653): DNAJC7 (Affinity Capture-MS), DNAJC7 (Affinity Capture-MS), DNAJC7 (Affinity Capture-MS), DNAJC7 (Affinity Capture-MS), DNAJC7 (Co-fractionation), DNAJC7 (Co-fractionation), DNAJC7 (Co-fractionation), DNAJC7 (Co-fractionation), DNAJC7 (Co-fractionation), DNAJC7 (Co-fractionation), HSPA4 (Co-fractionation), DNAJC7 (Affinity Capture-MS), DNAJC7 (Affinity Capture-MS), DNAJC7 (Proximity Label-MS), DNAJC7 (Proximity Label-MS)

ESM2 similar proteins: A7RL75, A8XHX1, F8RP11, O01422, O16259, O35814, O54981, P11144, P15705, P23231, P31948, P81127, Q05746, Q1EBV4, Q20683, Q23983, Q3ZBZ8, Q43468, Q4QR29, Q4R8N7, Q4X0I8, Q54DA8, Q54HL6, Q5AZQ5, Q5M7J9, Q5R8D8, Q5XEP2, Q5ZIK9, Q60864, Q62018, Q6DEU9, Q6INS3, Q6PD62, Q6WRS2, Q7S8M1, Q7ZU45, Q7ZWU1, Q8AVU9, Q8ILC1, Q8R3H9

Diamond homologs: A0A0D1E2P6, A0A0P0VG31, A0AIS3, A1A9Q7, A4XKA5, A7Z6W0, A7ZKA5, A7ZYV2, A8AI78, A8FFD1, A9MH53, A9N6S2, B1IV97, B1LJ04, B1X8V5, B1YKT0, B2TTP8, B4T2U5, B4TEN5, B4TSM3, B5BBH2, B5F1Z5, B5FR40, B5R049, B5R6G3, B5YU43, B6I976, B7LFA9, B7LP19, B7M8Y3, B7MIE6, B7MPT2, B7N3F5, B7NLC5, B7UNY3, B8I304, B9DNJ9, B9MJZ0, C0Q893, C1KVB9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 226 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
Signaling by ERBB2 ECD mutants	5	21.5×	1e-04
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	5	17.4×	3e-04
Transport of connexons to the plasma membrane	5	17.4×	3e-04
CD209 (DC-SIGN) signaling	5	16.6×	4e-04
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	16.6×	4e-04
Formation of tubulin folding intermediates by CCT/TriC	6	16.3×	1e-04
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	6	15.7×	1e-04
Gap junction trafficking and regulation	5	15.2×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
potassium ion homeostasis	5	19.0×	2e-03
cell volume homeostasis	5	14.9×	4e-03
positive regulation of ubiquitin-dependent protein catabolic process	5	13.9×	5e-03
response to unfolded protein	6	8.9×	8e-03
chloride transmembrane transport	7	8.2×	4e-03
monoatomic ion transport	9	7.0×	2e-03
protein import into nucleus	9	6.4×	3e-03
protein folding	11	5.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	1
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

2828 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41977256:CCTA:C	donor_loss	1.0000
17:41977258:TA:T	donor_loss	1.0000
17:41977259:A:AT	donor_loss	1.0000
17:41977260:CCT:C	donor_loss	1.0000
17:41977337:CAAG:C	acceptor_gain	1.0000
17:41977338:A:T	acceptor_gain	1.0000
17:41977340:G:C	acceptor_gain	1.0000
17:41977340:G:GC	acceptor_gain	1.0000
17:41977344:CA:C	acceptor_gain	1.0000
17:41977345:A:AC	acceptor_gain	1.0000
17:41977345:A:C	acceptor_gain	1.0000
17:41981851:TCA:T	donor_loss	1.0000
17:41981852:CACCA:C	donor_loss	1.0000
17:41981853:A:C	donor_loss	1.0000
17:41981853:ACCAC:A	donor_gain	1.0000
17:41981854:CCA:C	donor_gain	1.0000
17:41981854:CCACC:C	donor_gain	1.0000
17:41981872:T:TA	donor_gain	1.0000
17:41981878:T:C	donor_gain	1.0000
17:41981884:T:TA	donor_gain	1.0000
17:41981950:T:TA	donor_gain	1.0000
17:41982003:CCGAT:C	acceptor_gain	1.0000
17:41982004:CGAT:C	acceptor_gain	1.0000
17:41982004:CGATC:C	acceptor_gain	1.0000
17:41982005:GAT:G	acceptor_gain	1.0000
17:41982006:AT:A	acceptor_gain	1.0000
17:41982008:C:CA	acceptor_loss	1.0000
17:41982008:C:CC	acceptor_gain	1.0000
17:41982009:T:G	acceptor_loss	1.0000
17:41982013:G:GC	acceptor_gain	1.0000

AlphaMissense

3308 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41981926:A:G	L438P	1.000
17:41981926:A:T	L438H	1.000
17:41981939:C:G	A434P	1.000
17:41981955:G:C	F428L	1.000
17:41981955:G:T	F428L	1.000
17:41981956:A:G	F428S	1.000
17:41981957:A:G	F428L	1.000
17:41982004:C:G	R412P	1.000
17:41982257:G:T	P410Q	1.000
17:41982258:G:A	P410S	1.000
17:41982259:A:C	H409Q	1.000
17:41982259:A:T	H409Q	1.000
17:41982260:T:C	H409R	1.000
17:41982261:G:C	H409D	1.000
17:41982261:G:T	H409N	1.000
17:41982272:G:T	A405D	1.000
17:41982281:C:G	R402P	1.000
17:41982285:A:C	Y401D	1.000
17:41983608:C:G	A347P	1.000
17:41988751:C:G	R300P	1.000
17:41988862:C:T	G263E	1.000
17:41988863:C:A	G263W	1.000
17:41988893:C:G	A253P	1.000
17:41989507:C:T	G217D	1.000
17:41989508:C:G	G217R	1.000
17:41997203:C:G	R68P	1.000
17:42000544:C:T	G35E	1.000
17:42000545:C:G	G35R	1.000
17:42000545:C:T	G35R	1.000
17:41981924:A:G	S439P	0.999

dbSNP variants (sampled 300 via entrez): RS1000214922 (17:42002277 T>C), RS1000355625 (17:42016313 C>T), RS1000508921 (17:41995607 C>A,T), RS1000520242 (17:42008567 G>A), RS1000547201 (17:42000630 T>C), RS1000790179 (17:42014855 A>G), RS1001048648 (17:41988852 T>A,C), RS1001119797 (17:41981248 G>A), RS1001206637 (17:42011295 T>C), RS1001618177 (17:41984292 G>A,T), RS1001638224 (17:42011017 A>G,T), RS1001698918 (17:42011684 A>G,T), RS1001717286 (17:41992187 T>C), RS1001911122 (17:41976186 C>A), RS1002049063 (17:41990701 C>T)

Disease associations

OMIM: gene MIM:601964 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Limited	AD

Mondo (2): amyotrophic lateral sclerosis (MONDO:0004976), epilepsy (MONDO:0005027)

Orphanet (1): Amyotrophic lateral sclerosis (Orphanet:803)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0007354	Amyotrophic lateral sclerosis

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012305_4	Major depressive disorder x sex interaction	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008343	sex interaction measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050
D004827	Epilepsy	C10.228.140.490

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724907 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.00	IC50	1000	nM	CHEMBL5561795
5.70	IC50	2000	nM	CHEMBL5558181
5.40	IC50	4000	nM	CHEMBL5558644
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

4 with measured affinity, of 9 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N,N’-bis(3-carbamoyl-6-ethyl-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)pentanediamide	2084032: Inhibition of GST-tagged human DNAJC7 expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay	ic50	1.0000	uM
N,N’-bis(3-carbamoyl-4,5-dimethylthiophen-2-yl)pentanediamide	2084032: Inhibition of GST-tagged human DNAJC7 expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay	ic50	2.0000	uM
methyl 2-[[2-[[5,6-bis(furan-2-yl)-1,2,4-triazin-3-yl]sulfanyl]acetyl]amino]-4,5-dimethylthiophene-3-carboxylate	2084032: Inhibition of GST-tagged human DNAJC7 expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay	ic50	4.0000	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179011: Inhibition of DNAJC7 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
Vehicle Emissions	decreases reaction, increases expression, affects expression, increases reaction	3
Particulate Matter	increases reaction, decreases reaction, increases expression, affects expression	3
Arsenic Trioxide	affects binding, decreases reaction, decreases expression	2
Acetaminophen	increases expression, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Valproic Acid	affects expression, decreases expression	2
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects localization, affects cotreatment	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	decreases methylation	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
corosolic acid	decreases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Carbamazepine	affects expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5524505	Binding	Inhibition of GST-tagged human DNAJC7 expressed in Escherichia coli BL21 (DE3) using NH2-EDASRMEEVD-COOH peptide as substrate preincubated for 15 mins followed by substrate addition measured after 15 mins by Alpha Screen assay	Structure-based discovery of small molecule inhibitors of FKBP51-Hsp90 protein-protein interaction. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9DI	Ubigene HEK293 DNAJC7 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	PHASE3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	PHASE3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	PHASE3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	PHASE3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	PHASE3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	PHASE3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	PHASE3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	PHASE3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	PHASE3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	PHASE3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	PHASE3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	PHASE3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	PHASE3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	PHASE3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	PHASE3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	PHASE3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	PHASE3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	PHASE3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	PHASE3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	PHASE3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	PHASE3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	PHASE3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	PHASE3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	PHASE3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	PHASE3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	PHASE3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS