VPS39

Summary

VPS39 (VPS39 subunit of HOPS complex, HGNC:20593) is a protein-coding gene on chromosome 15q15.1, encoding Vam6/Vps39-like protein (Q96JC1). Regulator of TGF-beta/activin signaling, inhibiting SMAD3- and activating SMAD2-dependent transcription. It is a selective cancer dependency (DepMap: 13.8% of cell lines).

This gene encodes a protein that may promote clustering and fusion of late endosomes and lysosomes. The protein may also act as an adaptor protein that modulates the transforming growth factor-beta response by coupling the transforming growth factor-beta receptor complex to the Smad pathway. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 23339 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 138 total
• Cancer dependency (DepMap): dependent in 13.8% of screened cell lines
• MANE Select transcript: NM_015289

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20593
Approved symbol	VPS39
Name	VPS39 subunit of HOPS complex
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0770, VAM6
Ensembl gene	ENSG00000166887
Ensembl biotype	protein_coding
OMIM	612188
Entrez	23339

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 15 protein_coding, 9 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000318006, ENST00000348544, ENST00000561797, ENST00000561818, ENST00000562258, ENST00000562662, ENST00000563692, ENST00000564994, ENST00000568029, ENST00000568357, ENST00000568755, ENST00000570023, ENST00000570062, ENST00000614932, ENST00000906182, ENST00000928541, ENST00000928542, ENST00000928543, ENST00000928544, ENST00000928545, ENST00000961227, ENST00000961228, ENST00000961229, ENST00000961230, ENST00000961231, ENST00000961232, ENST00000961233

RefSeq mRNA: 2 — MANE Select: NM_015289 NM_001301138, NM_015289

CCDS: CCDS10083, CCDS73710

Canonical transcript exons

ENST00000318006 — 25 exons

Exon	Start	End
ENSE00001107442	42169724	42169866
ENSE00001107443	42191496	42191560
ENSE00001107449	42191125	42191167
ENSE00001107451	42167394	42167537
ENSE00001107454	42173723	42173852
ENSE00001107460	42178450	42178570
ENSE00001107486	42164358	42164486
ENSE00001107492	42184517	42184700
ENSE00001149896	42166772	42166913
ENSE00001845469	42158701	42160829
ENSE00001928144	42208081	42208304
ENSE00003466891	42199896	42199961
ENSE00003479936	42163626	42163728
ENSE00003510837	42178218	42178338
ENSE00003511056	42161682	42161773
ENSE00003524375	42162032	42162166
ENSE00003563590	42165718	42165816
ENSE00003564452	42166159	42166232
ENSE00003576190	42187758	42187856
ENSE00003586667	42163350	42163395
ENSE00003589901	42189114	42189208
ENSE00003611279	42187271	42187363
ENSE00003618553	42164996	42165113
ENSE00003622863	42162332	42162481
ENSE00003629108	42166563	42166649

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 95.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.8050 / max 237.9970, expressed in 1812 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149547	22.8050	1812

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	95.30	gold quality
granulocyte	CL:0000094	95.08	gold quality
mucosa of stomach	UBERON:0001199	94.87	gold quality
skin of leg	UBERON:0001511	94.86	gold quality
right lobe of thyroid gland	UBERON:0001119	94.84	gold quality
skin of abdomen	UBERON:0001416	94.65	gold quality
left lobe of thyroid gland	UBERON:0001120	94.55	gold quality
adenohypophysis	UBERON:0002196	94.40	gold quality
apex of heart	UBERON:0002098	94.35	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.26	gold quality
right adrenal gland cortex	UBERON:0035827	94.16	gold quality
right adrenal gland	UBERON:0001233	94.09	gold quality
body of pancreas	UBERON:0001150	94.07	gold quality
stromal cell of endometrium	CL:0002255	94.03	gold quality
left adrenal gland cortex	UBERON:0035825	93.95	gold quality
left adrenal gland	UBERON:0001234	93.94	gold quality
thyroid gland	UBERON:0002046	93.91	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.83	gold quality
lower esophagus	UBERON:0013473	93.81	gold quality
pituitary gland	UBERON:0000007	93.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.73	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.70	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.65	gold quality
metanephros cortex	UBERON:0010533	93.64	gold quality
minor salivary gland	UBERON:0001830	93.62	gold quality
spleen	UBERON:0002106	93.62	gold quality
right lung	UBERON:0002167	93.62	gold quality
descending thoracic aorta	UBERON:0002345	93.62	gold quality
right frontal lobe	UBERON:0002810	93.60	gold quality
cerebellar hemisphere	UBERON:0002245	93.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting VPS39, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-7153-3P	99.00	65.35	608
HSA-MIR-9898	99.00	67.89	500
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-330-5P	98.73	67.63	1788

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• propose that TLP might regulate the balance of Smad2 and Smad3 signaling by localizing Smad4 intracellularly, thus contributing to cellular specificity of TGF-beta transcriptional responses in both normal and pathophysiology (PMID:12941698)
• although only TBC1D15/Rab7-GAP altered Rab7-GTP levels, both Rab7-GAP and mVps39 regulate lysosomal morphology and play a role in maintaining growth factor dependence (PMID:20363736)
• Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus (PMID:21454559)
• Vps39 knockdown impairs late endosome fusion and fusion between late endosomes and lysosomes. (PMID:23167963)
• TLP likely acts as a molecular modulator capable of altering the balance of Smad3- and Smad2-dependent signaling through regulation of phosphorylation, thus facilitating collagen synthesis in fibroblasts. (PMID:23418473)
• TLP expression contributes to hypertrophic scar formation and contraction. (PMID:25655281)
• VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics. (PMID:33893273)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	vps39	ENSDARG00000074471
mus_musculus	Vps39	ENSMUSG00000027291
rattus_norvegicus	Vps39	ENSRNOG00000008316
drosophila_melanogaster	Vps39	FBGN0038593
caenorhabditis_elegans		WBGENE00011625

Paralogs (1): TGFBRAP1 (ENSG00000135966)

Protein

Protein identifiers

Vam6/Vps39-like protein — Q96JC1 (reviewed: Q96JC1)

Alternative names: TRAP1-like protein

All UniProt accessions (2): Q96JC1, H3BTU0

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of TGF-beta/activin signaling, inhibiting SMAD3- and activating SMAD2-dependent transcription. Acts by interfering with SMAD3/SMAD4 complex formation, this would lead to inhibition of SMAD3-dependent transcription and relieve SMAD3 inhibition of SMAD2-dependent promoters, thus increasing SMAD2-dependent transcription. Does not affect TGF-beta-induced SMAD2 or SMAD3 phosphorylation, nor SMAD2/SMAD4 complex formation. Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Acts as a component of the HOPS endosomal tethering complex. This complex is proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. Involved in homotypic vesicle fusions between late endosomes and in heterotypic fusions between late endosomes and lysosomes. Required for fusion of endosomes and autophagosomes with lysosomes.

Subunit / interactions. Homooligomer. Interacts with TGFBR2 and, less efficiently, with TGFBR1; interaction with TGFBR2 is independent of the receptor kinase activity and of the presence of TGF-beta. Also interacts with ACVR2B, but not with BMPR2. Interacts with SMAD4, preferentially following TGF-beta treatment. Does not interact with SAMD2 or SMAD3. Component of the homotypic fusion and vacuole protein sorting (HOPS) complex; the core of which composed of the class C Vps proteins VPS11, VPS16, VPS18 and VPS33A, is associated with VPS39 and VPS41. Interacts with PLEKHM2; involved in VPS39 recruitment to ARL8B-containing lysosomes. Associates with adapter protein complex 3 (AP-3) and clathrin:AP-3 complexes. Interacts with STX17; this interaction is increased in the absence of TMEM39A. Interacts with RAB7, RAB2A and RAB2B. Interacts with RAB2A (GTP-bound); the interaction contributes to obtaining a functional HOPS complex that promotes autophagosome-lysosome membrane fusion driven by STX17-SNAP29-VAMP8. Interacts with RAB39A (GTP-bound) and RAB39B (GTP-bound); interaction with RAB39A contributes to obtaining a functional HOPS complex. (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 ORF3A protein; the interaction is direct and sequestrates VPS39, thereby preventing HOPS complex from interacting with the autophagosomal SNARE protein STX17. ORF3A enhances the interaction of VPS39 with VPS11 and VPS18, while its interaction with the VPS16:VPS33A module is attenuated.

Subcellular location. Cytoplasm. Lysosome membrane. Late endosome membrane.

Tissue specificity. Widely expressed, with highest levels in heart, skeletal muscle, kidney, pancreas, brain, placenta and spleen.

Similarity. Belongs to the VAM6/VPS39 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96JC1-1	1	yes
Q96JC1-2	2

RefSeq proteins (2): NP_001288067, NP_056104* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000547	Clathrin_H-chain/VPS_repeat	Repeat
IPR001180	CNH_dom	Domain
IPR019452	VPS39/TGF_beta_rcpt-assoc_1	Domain
IPR019453	VPS39/TGFA1_Znf	Domain
IPR032914	Vam6/VPS39/TRAP1	Family

Pfam: PF00780, PF10366, PF10367

UniProt features (11 total): sequence conflict 3, strand 3, chain 1, domain 1, helix 1, repeat 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6ZE9	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JC1-F1	88.39	0.55

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9754560	SARS-CoV-2 modulates autophagy

MSigDB gene sets: 185 (showing top): GOBP_LYSOSOMAL_TRANSPORT, GOBP_VACUOLE_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, CGGAARNGGCNG_UNKNOWN, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GOBP_MEMBRANE_FUSION, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_MACROAUTOPHAGY, BROWNE_HCMV_INFECTION_48HR_DN, CADWELL_ATG16L1_TARGETS_DN

GO Biological Process (10): intracellular protein transport (GO:0006886), autophagy (GO:0006914), endosome to lysosome transport (GO:0008333), endocytic recycling (GO:0032456), endosomal vesicle fusion (GO:0034058), regulation of SNARE complex assembly (GO:0035542), autophagosome-lysosome fusion (GO:0061909), late endosome to lysosome transport (GO:1902774), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (2): molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (12): cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), late endosome (GO:0005770), endosome membrane (GO:0010008), membrane (GO:0016020), AP-3 adaptor complex (GO:0030123), HOPS complex (GO:0030897), late endosome membrane (GO:0031902), lysosomal HOPS complex (GO:1902501), lysosome (GO:0005764), endosome (GO:0005768), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular protein localization	2
lysosomal transport	2
intercellular transport	2
vesicle fusion	2
transport	2
binding	2
endosome	2
protein transport	1
intracellular transport	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
vesicle-mediated transport	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
SNARE complex assembly	1
regulation of protein-containing complex assembly	1
macroautophagy	1
establishment of protein localization	1
cellular process	1
molecular_function	1
intracellular anatomical structure	1
lysosome	1
lytic vacuole membrane	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
AP-type membrane coat adaptor complex	1
membrane protein complex	1
vesicle tethering complex	1
late endosome	1
endosome membrane	1
lysosomal membrane	1
vacuolar HOPS complex	1
lytic vacuole	1
endomembrane system	1
cytoplasmic vesicle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

2264 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VPS39	VPS16	Q9H269	999
VPS39	VPS18	Q9P253	998
VPS39	VPS11	Q9H270	998
VPS39	VPS33A	Q96AX1	993
VPS39	VPS41	P49754	983
VPS39	TOMM40	O96008	925
VPS39	VPS8	Q8N3P4	903
VPS39	RAB2A	P08886	843
VPS39	STX17	P56962	831
VPS39	SMAD4	Q13485	779
VPS39	VPS45	Q9NRW7	777
VPS39	NSF	P46459	774
VPS39	CCZ1B	P86790	742
VPS39	TGFBRAP1	Q8WUH2	726
VPS39	CLTC	Q00610	720

IntAct

80 interactions, top by confidence:

A	B	Type	Score
	VPS39	psi-mi:“MI:0407”(direct interaction)	0.960
	VPS39	psi-mi:“MI:0403”(colocalization)	0.960
	VPS39	psi-mi:“MI:0915”(physical association)	0.960
VPS39		psi-mi:“MI:0915”(physical association)	0.960
VPS39		psi-mi:“MI:0407”(direct interaction)	0.960
VPS39		psi-mi:“MI:0914”(association)	0.960
VPS39		psi-mi:“MI:0403”(colocalization)	0.960
	VPS39	psi-mi:“MI:0914”(association)	0.960
VPS18	VPS41	psi-mi:“MI:0914”(association)	0.800
VPS11	VPS39	psi-mi:“MI:0915”(physical association)	0.740
	HMOX1	psi-mi:“MI:0914”(association)	0.740
PLEKHM1	VPS41	psi-mi:“MI:0914”(association)	0.740
VPS11	VPS41	psi-mi:“MI:0914”(association)	0.710
	VPS41	psi-mi:“MI:0914”(association)	0.690
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
PLEKHM1	VPS39	psi-mi:“MI:0915”(physical association)	0.610
PLEKHM1	VPS33A	psi-mi:“MI:0914”(association)	0.600
VPS39	STX17	psi-mi:“MI:0915”(physical association)	0.590
USP54	DYRK1A	psi-mi:“MI:0914”(association)	0.550
ZNF263	AHCYL1	psi-mi:“MI:0914”(association)	0.530
VPS39	VPS18	psi-mi:“MI:0915”(physical association)	0.500
VPS39	RAB7A	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (112): VPS39 (Affinity Capture-MS), VPS39 (Affinity Capture-MS), VPS39 (Reconstituted Complex), VPS39 (Reconstituted Complex), VPS39 (Affinity Capture-MS), VPS39 (Two-hybrid), VPS39 (Affinity Capture-Western), VPS39 (Affinity Capture-Western), VPS39 (Affinity Capture-Western), VPS39 (Synthetic Lethality), VPS11 (Affinity Capture-MS), RPS6KC1 (Affinity Capture-MS), VPS39 (Affinity Capture-MS), VPS39 (Affinity Capture-MS), USP54 (Affinity Capture-MS)

ESM2 similar proteins: A0A8J1LLF7, A0A974H8H3, A0MQH0, A4FUD6, A5HK05, B3DLA6, P11029, P11497, P42694, P54198, Q13085, Q25BN1, Q28559, Q4R4U1, Q504Q3, Q5R5F8, Q5R660, Q5R8I6, Q5RCC1, Q5SWU9, Q5ZIT8, Q6DFV5, Q6IE70, Q6NYU2, Q6P1X5, Q6TUI4, Q6TV19, Q80YV4, Q8BGF7, Q8BHL5, Q8BPU7, Q8C176, Q8CIQ7, Q8IZD9, Q8K0F1, Q8R418, Q8R5L3, Q8VHE0, Q923S8, Q92556

Diamond homologs: Q1ZXS5, Q8R5L3, Q96JC1, Q9VEA2

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
VPS39	“form complex”	“HOPS tethering complex”	binding
TGFBR2	“up-regulates activity”	VPS39	binding
TGFBR1	“up-regulates activity”	VPS39	binding
ACVR1	“up-regulates activity”	VPS39	binding
VPS39	“down-regulates activity”	SMAD4	relocalization
VPS39	“down-regulates quantity”	SMAD3/SMAD4	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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.

GO biological processes:

GO term	Partners	Fold	FDR
endosomal vesicle fusion	5	114.6×	1e-07
endosome to lysosome transport	7	48.1×	7e-08
intracellular protein transport	7	9.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4328 predictions. Top by Δscore:

Variant	Effect	Δscore
15:42160830:C:CC	acceptor_gain	1.0000
15:42161676:GCTCA:G	donor_loss	1.0000
15:42161677:CTCA:C	donor_loss	1.0000
15:42161678:TCA:T	donor_loss	1.0000
15:42161679:CA:C	donor_loss	1.0000
15:42161681:C:CG	donor_loss	1.0000
15:42161772:ACC:A	acceptor_loss	1.0000
15:42161775:T:C	acceptor_loss	1.0000
15:42162028:CTAC:C	donor_loss	1.0000
15:42162030:A:AC	donor_gain	1.0000
15:42162030:AC:A	donor_gain	1.0000
15:42162031:C:CC	donor_gain	1.0000
15:42162031:C:CT	donor_loss	1.0000
15:42162031:CC:C	donor_gain	1.0000
15:42162031:CCCT:C	donor_gain	1.0000
15:42162162:AGGGC:A	acceptor_gain	1.0000
15:42162163:GGGC:G	acceptor_gain	1.0000
15:42162164:GGC:G	acceptor_gain	1.0000
15:42162165:GC:G	acceptor_gain	1.0000
15:42162166:CC:C	acceptor_gain	1.0000
15:42162166:CCTAG:C	acceptor_loss	1.0000
15:42162167:C:CC	acceptor_gain	1.0000
15:42162167:CTA:C	acceptor_loss	1.0000
15:42162174:C:CT	acceptor_gain	1.0000
15:42162175:A:T	acceptor_gain	1.0000
15:42162477:TACAC:T	acceptor_gain	1.0000
15:42162488:C:CT	acceptor_gain	1.0000
15:42163344:ACT:A	donor_loss	1.0000
15:42163345:C:CA	donor_loss	1.0000
15:42163346:TCACA:T	donor_loss	1.0000

AlphaMissense

5766 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:42161703:C:T	C855Y	1.000
15:42161704:A:G	C855R	1.000
15:42161713:A:G	C852R	1.000
15:42166574:A:G	L543P	1.000
15:42166637:A:G	L522P	1.000
15:42166646:A:G	L519P	1.000
15:42166801:A:G	L508P	1.000
15:42166810:A:G	L505P	1.000
15:42166837:A:G	L496P	1.000
15:42167410:A:G	L465P	1.000
15:42167413:A:G	L464P	1.000
15:42167422:T:A	D461V	1.000
15:42167422:T:G	D461A	1.000
15:42167423:C:G	D461H	1.000
15:42169731:A:G	L420P	1.000
15:42169743:A:G	L416P	1.000
15:42178258:A:G	L318P	1.000
15:42178303:A:T	V303D	1.000
15:42178519:C:G	R268P	1.000
15:42184541:A:G	W243R	1.000
15:42184541:A:T	W243R	1.000
15:42199917:A:C	Y40D	1.000
15:42199922:A:G	L38P	1.000
15:42199925:A:G	L37P	1.000
15:42199943:C:T	G31E	1.000
15:42199952:A:G	L28P	1.000
15:42160784:A:C	C877W	0.999
15:42160785:C:G	C877S	0.999
15:42160785:C:T	C877Y	0.999
15:42160786:A:G	C877R	0.999

dbSNP variants (sampled 300 via entrez): RS1000119857 (15:42163858 T>C), RS1000283906 (15:42185118 C>T), RS1000296486 (15:42177996 C>A,T), RS1000308133 (15:42186594 T>C), RS1000358329 (15:42186373 G>A), RS1000367833 (15:42171146 T>C), RS1000377721 (15:42166972 G>C), RS1000407701 (15:42178318 G>A,C), RS1000477405 (15:42204855 T>C), RS1000543083 (15:42206421 G>C,T), RS1000639469 (15:42192884 T>G), RS1000746832 (15:42187448 T>G), RS1000773807 (15:42192266 G>T), RS1000976553 (15:42180346 G>A), RS1001078010 (15:42174223 G>A,T)

Disease associations

OMIM: gene MIM:612188 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): cerebellar ataxia (MONDO:0000437)

Orphanet (1): Rare ataxia (Orphanet:102002)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, decreases expression	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression	1
Arbutin	increases expression	1
Benzo(a)pyrene	increases methylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Bucladesine	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Selenium	affects cotreatment, increases expression	1
Vitamin E	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1
Medroxyprogesterone Acetate	affects cotreatment, increases expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2NT	HAP1 VPS39 (-) 1	Cancer cell line	Male
CVCL_E2NU	HAP1 VPS39 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT04107740	PHASE4	COMPLETED	C-Trelin Orally Disintegrated(OD) Tablet 5mg in Ataxia Due to Spinocerebellar Degeneration
NCT01970098	PHASE3	COMPLETED	A Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970111	PHASE3	COMPLETED	An Extension Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970124	PHASE3	COMPLETED	A Long-Term Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970137	PHASE3	COMPLETED	A 24-week Open-label Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT02889302	PHASE3	COMPLETED	An Additional Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT03408080	PHASE3	ACTIVE_NOT_RECRUITING	Open Pilot Trial of BHV-4157
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT03901638	PHASE3	TERMINATED	Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
NCT07040137	PHASE3	RECRUITING	Confirmatory Study 3 of KPS-0373 in Patients With Spinocerebellar Degeneration
NCT00034242	PHASE2	COMPLETED	High-Dose Intravenous Immunoglobulin to Treat Cerebellar Degeneration
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00863538	PHASE2	COMPLETED	Phase II Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01004016	PHASE2	COMPLETED	A Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01350440	PHASE2	COMPLETED	Safety and Efficacy of Intravenous Immune Globulin in Treating Spinocerebellar Ataxia
NCT02540655	PHASE2	COMPLETED	Efficacy and Safety Study of Stemchymal® in Polyglutamine Spinocerebellar Ataxia
NCT03932669	PHASE2	COMPLETED	Effect of Nilotinib in Cerebellar Ataxia Patients
NCT04301284	PHASE2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT05125666	PHASE2	UNKNOWN	Efficacy of Dual Task Training on Children With Ataxia After Medulloblastoma Resection
NCT06397274	PHASE2	NOT_YET_RECRUITING	Stemchymal® for Polyglutamine Spinocerebellar Ataxia
NCT00683943	PHASE1	COMPLETED	Lithium Treatment for Patients With Spinocerebellar Ataxia Type I
NCT02287064	PHASE1	UNKNOWN	An Open-label Trial of Intravenous Immune Globulin (IVIG)in Treating Spinocerebellar Ataxias
NCT05157802	PHASE1	ACTIVE_NOT_RECRUITING	Promoting Physical Activity Engagement for People With Early-stage Cerebellar Ataxia
NCT01104649	PHASE2/PHASE3	COMPLETED	Efficacy of Riluzole in Hereditary Cerebellar Ataxia
NCT02960893	PHASE2/PHASE3	COMPLETED	Trial in Adult Participants With Spinocerebellar Ataxia (SCA)
NCT00244361	PHASE1/PHASE2	COMPLETED	Effectiveness of Rituximab in Pediatric OMS Patients.
NCT01649687	PHASE1/PHASE2	COMPLETED	Treatment of Cerebellar Ataxia With Mesenchymal Stem Cells
NCT01958177	PHASE1/PHASE2	UNKNOWN	Clinical Study to Evaluate the Safety and Efficacy BMMNC in Cerebellar Ataxia
NCT02829268	PHASE1/PHASE2	COMPLETED	A Clinical Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome
NCT00001324	Not specified	COMPLETED	PET Scan to Study Brain Control of Human Movement
NCT00006492	Not specified	COMPLETED	Gluten-Free Diet in Patients With Gluten Sensitivity and Cerebellar Ataxia
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00272272	Not specified	COMPLETED	Fall Prevention in a Geriatric Nursing Home Setting Using the Music of Nolwenn Leroy
NCT00654251	Not specified	COMPLETED	Measuring Neurological Impairment and Functional Visual Assessment In Spinocerebellar Ataxias
NCT00692861	Not specified	COMPLETED	Autoimmunity in Neurologic Complications of Celiac Disease
NCT01037777	Not specified	COMPLETED	RISCA : Prospective Study of Individuals at Risk for SCA1, SCA2, SCA3, SCA6, SCA7
NCT01307176	Not specified	COMPLETED	Exercise Training Program for Cerebellar Ataxia
NCT01428531	Not specified	COMPLETED	Special Drug Use Investigation for Arixtra® (Fondaparinux) Venous Thromboembolism Treatment