VPS18

Summary

VPS18 (VPS18 core subunit of CORVET and HOPS complexes, HGNC:15972) is a protein-coding gene on chromosome 15q15.1, encoding Vacuolar protein sorting-associated protein 18 homolog (Q9P253). Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. It is a common-essential gene (DepMap: required in 91.6% of cancer cell lines).

Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human homolog of yeast class C Vps18 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway.

Source: NCBI Gene 57617 — RefSeq curated summary.

At a glance

• Gene–disease (curated): leukodystrophy (No Known Disease Relationship, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 179 total
• Cancer dependency (DepMap): dependent in 91.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_020857

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15972
Approved symbol	VPS18
Name	VPS18 core subunit of CORVET and HOPS complexes
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1475, PEP3
Ensembl gene	ENSG00000104142
Ensembl biotype	protein_coding
OMIM	608551
Entrez	57617

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000220509, ENST00000558474, ENST00000558855, ENST00000882105, ENST00000943645

RefSeq mRNA: 1 — MANE Select: NM_020857 NM_020857

CCDS: CCDS10069

Canonical transcript exons

ENST00000220509 — 5 exons

Exon	Start	End
ENSE00000338834	40899144	40901014
ENSE00000675644	40895938	40896079
ENSE00000675656	40902616	40903975
ENSE00001353029	40894450	40894859
ENSE00003557429	40898907	40898998

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 90.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3139 / max 58.0096, expressed in 1806 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146150	10.2793	1798
146149	1.9160	1288
146151	1.1186	653

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	90.50	gold quality
tendon of biceps brachii	UBERON:0008188	90.15	gold quality
kidney epithelium	UBERON:0004819	88.63	gold quality
stromal cell of endometrium	CL:0002255	87.69	gold quality
apex of heart	UBERON:0002098	86.06	gold quality
cardiac muscle of right atrium	UBERON:0003379	85.65	gold quality
left ventricle myocardium	UBERON:0006566	85.33	gold quality
tibialis anterior	UBERON:0001385	85.16	silver quality
blood	UBERON:0000178	83.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.16	gold quality
islet of Langerhans	UBERON:0000006	83.14	gold quality
prefrontal cortex	UBERON:0000451	82.94	gold quality
leukocyte	CL:0000738	82.82	gold quality
gastrocnemius	UBERON:0001388	82.79	gold quality
monocyte	CL:0000576	82.67	gold quality
heart left ventricle	UBERON:0002084	82.60	gold quality
granulocyte	CL:0000094	82.59	gold quality
muscle of leg	UBERON:0001383	82.53	gold quality
ileal mucosa	UBERON:0000331	82.29	gold quality
cardiac ventricle	UBERON:0002082	82.17	gold quality
decidua	UBERON:0002450	82.07	gold quality
right adrenal gland	UBERON:0001233	81.91	gold quality
left adrenal gland	UBERON:0001234	81.88	gold quality
right adrenal gland cortex	UBERON:0035827	81.78	gold quality
right coronary artery	UBERON:0001625	81.63	gold quality
left adrenal gland cortex	UBERON:0035825	81.59	gold quality
descending thoracic aorta	UBERON:0002345	81.51	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.34	gold quality
lower esophagus	UBERON:0013473	81.31	gold quality
thoracic aorta	UBERON:0001515	81.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting VPS18, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-6784-3P	98.39	64.88	662
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-6862-3P	97.92	64.86	531
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-5699-5P	97.36	67.03	1014
HSA-MIR-1225-3P	97.29	64.60	876
HSA-MIR-644A	96.02	66.52	786
HSA-MIR-4323	93.93	63.89	656
HSA-MIR-6089	89.72	61.35	324

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 91.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 6)

• hVPS18 may play an important role in regulation of SNK activity through its ubiquitin ligase (PMID:16203730)
• ubiquitin binding and ubiquitylation of GGA3-GAT domain are mutually inseparable through a ubiquitin ligase activity of hVPS18 (PMID:16996030)
• Depletion of hVps18 or hMon2 reduced the efficient production of infectious HIV-1 virions in human cells. (PMID:21450827)
• VPS18 recruits VPS41 to the human HOPS complex via a RING-RING interaction (PMID:28931724)
• Study characterized the ubiquitinomes of Vps11/18 and demonstrated that these two factors are involved in the regulation of signal transduction by protein ubiquitination. VPS11/18 regulate several signaling factors and pathways, including Wnt, estrogen receptor alpha (ERalpha), and NFkappaB. (PMID:31015428)
• Targeting of VPS18 by the lysosomotropic agent RDN reverses TFE3-mediated drug resistance. (PMID:34099617)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	vps18	ENSDARG00000070433
mus_musculus	Vps18	ENSMUSG00000034216
rattus_norvegicus	Vps18	ENSRNOG00000013689
drosophila_melanogaster	dor	FBGN0000482
caenorhabditis_elegans		WBGENE00021058

Paralogs (1): VPS11 (ENSG00000160695)

Protein

Protein identifiers

Vacuolar protein sorting-associated protein 18 homolog — Q9P253 (reviewed: Q9P253)

All UniProt accessions (3): Q9P253, H0YLM6, H0YMC9

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are 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. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations. Required for fusion of endosomes and autophagosomes with lysosomes. Involved in dendrite development of Pukinje cells.

Subunit / interactions. Core component of at least two putative endosomal tethering complexes, the homotypic fusion and vacuole protein sorting (HOPS) complex and the class C core vacuole/endosome tethering (CORVET) complex. Their common core is composed of the class C Vps proteins VPS11, VPS16, VPS18 and VPS33A, which in HOPS further associates with VPS39 and VPS41 and in CORVET with VPS8 and TGFBRAP1. Interacts with RAB5C. Interacts with HOOK1. Interacts with STX7, MON1B. Associates with adaptor protein complex 3 (AP-3) and clathrin:AP-3 complexes. Interacts with SYNPO2. Interacts with PLEKHM1.

Subcellular location. Late endosome membrane. Lysosome membrane. Early endosome. Cytoplasmic vesicle. Autophagosome. Clathrin-coated vesicle.

Tissue specificity. Ubiquitous. Expression was highest in heart and low in lung.

Similarity. Belongs to the VPS18 family.

RefSeq proteins (1): NP_065908* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000547	Clathrin_H-chain/VPS_repeat	Repeat
IPR007810	Pep3/Vps18_beta-prop	Domain
IPR058919	Pep3/Vps18_RING_C	Domain

Pfam: PF05131, PF26148

UniProt features (15 total): modified residue 7, coiled-coil region 2, initiator methionine 1, chain 1, sequence variant 1, repeat 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P253-F1	79.32	0.16

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 (7): 13, 362, 689, 912, 2, 3, 11

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 193 (showing top): GOBP_LYSOSOMAL_TRANSPORT, GOBP_ENDOSOME_ORGANIZATION, GOBP_VACUOLE_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_MEMBRANE_FUSION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_ESTROGEN_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_VACUOLAR_TRANSPORT, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_REGULATION_OF_INTRACELLULAR_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (15): intracellular protein transport (GO:0006886), obsolete vesicle docking involved in exocytosis (GO:0006904), autophagy (GO:0006914), endosome organization (GO:0007032), lysosome organization (GO:0007040), endosome to lysosome transport (GO:0008333), protein ubiquitination (GO:0016567), negative regulation of intracellular estrogen receptor signaling pathway (GO:0033147), endosomal vesicle fusion (GO:0034058), regulation of SNARE complex assembly (GO:0035542), symbiont entry into host cell (GO:0046718), organelle fusion (GO:0048284), regulation of synaptic vesicle exocytosis (GO:2000300), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (7): actin binding (GO:0003779), zinc ion binding (GO:0008270), syntaxin binding (GO:0019905), protein-macromolecule adaptor activity (GO:0030674), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (18): lysosome (GO:0005764), lysosomal membrane (GO:0005765), endosome (GO:0005768), early endosome (GO:0005769), late endosome (GO:0005770), autophagosome (GO:0005776), actin filament (GO:0005884), endosome membrane (GO:0010008), AP-3 adaptor complex (GO:0030123), clathrin-coated vesicle (GO:0030136), HOPS complex (GO:0030897), late endosome membrane (GO:0031902), CORVET complex (GO:0033263), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), endomembrane system (GO:0012505), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

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
endosome	4
cellular anatomical structure	3
intracellular protein localization	2
transport	2
vacuole	2
vesicle tethering complex	2
synapse	2
protein transport	1
intracellular transport	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
endomembrane system organization	1
vesicle organization	1
lytic vacuole organization	1
lysosomal transport	1
intercellular transport	1
vesicle-mediated transport	1
protein modification by small protein conjugation	1
estrogen receptor signaling pathway	1
negative regulation of intracellular steroid hormone receptor signaling pathway	1
regulation of intracellular estrogen receptor signaling pathway	1
vesicle fusion	1
SNARE complex assembly	1
regulation of protein-containing complex assembly	1
viral life cycle	1
symbiont entry into host	1
organelle organization	1
synaptic vesicle exocytosis	1
regulation of neurotransmitter secretion	1
regulation of regulated secretory pathway	1
establishment of protein localization	1
cellular process	1
cytoskeletal protein binding	1
transition metal ion binding	1
SNARE binding	1
protein binding	1
molecular adaptor activity	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1

Protein interactions and networks

STRING

1476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VPS18	VPS39	Q96JC1	998
VPS18	VPS16	Q9H269	998
VPS18	VPS33A	Q96AX1	997
VPS18	VPS11	Q9H270	993
VPS18	VPS41	P49754	976
VPS18	VPS8	Q8N3P4	943
VPS18	TGFBRAP1	Q8WUH2	932
VPS18	MPG	P29372	830
VPS18	VPS45	Q9NRW7	802
VPS18	PGC	P20142	784
VPS18	STX17	P56962	739
VPS18	CACNA1S	Q13698	688
VPS18	VPS25	Q9BRG1	668
VPS18	CCZ1B	P86790	663
VPS18	RBSN	Q9H1K0	657

IntAct

149 interactions, top by confidence:

A	B	Type	Score
VPS16	VPS33A	psi-mi:“MI:0914”(association)	0.950
VPS11	TGFBRAP1	psi-mi:“MI:0914”(association)	0.850
VPS18	VPS16	psi-mi:“MI:0914”(association)	0.840
VPS18	VPS16	psi-mi:“MI:0915”(physical association)	0.840
VPS16	VPS18	psi-mi:“MI:0915”(physical association)	0.840
VPS11	VPS18	psi-mi:“MI:0915”(physical association)	0.830
VPS11	VPS16	psi-mi:“MI:0914”(association)	0.800
VPS16	VPS11	psi-mi:“MI:0914”(association)	0.800
VPS18	VPS41	psi-mi:“MI:0915”(physical association)	0.800
VPS18	VPS41	psi-mi:“MI:0914”(association)	0.800
PLEKHM1	VPS41	psi-mi:“MI:0914”(association)	0.740
VPS18	VPS33A	psi-mi:“MI:0915”(physical association)	0.720
VPS33A	VPS18	psi-mi:“MI:0915”(physical association)	0.720
VPS11	VPS41	psi-mi:“MI:0914”(association)	0.710
VPS11	Vps33a	psi-mi:“MI:0914”(association)	0.620
Vps33a	VPS11	psi-mi:“MI:0915”(physical association)	0.620
PLEKHM1	VPS33A	psi-mi:“MI:0914”(association)	0.600
VPS33A	STX17	psi-mi:“MI:0914”(association)	0.540
CT55	BLTP3B	psi-mi:“MI:0914”(association)	0.530

BioGRID (243): VPS18 (Affinity Capture-MS), VPS18 (Affinity Capture-MS), VPS18 (Affinity Capture-MS), VPS18 (Affinity Capture-MS), VPS18 (Reconstituted Complex), VPS18 (Reconstituted Complex), VPS18 (Co-fractionation), VPS18 (Affinity Capture-MS), VPS18 (Affinity Capture-Western), VPS33A (Affinity Capture-Western), VPS18 (Affinity Capture-Western), VPS16 (Affinity Capture-Western), VPS11 (Affinity Capture-MS), VPS16 (Affinity Capture-MS), VPS33A (Affinity Capture-MS)

ESM2 similar proteins: A0A5F8AH41, A0AVI4, A0JMH2, A1Y9I9, A5WVX1, B0X4N1, B4P925, D3ZX08, O55171, O88512, O95050, O97972, P0DPD7, P0DPE0, P0DPE1, P10937, P10938, P11086, P40935, P40936, Q06AU9, Q08DK0, Q14CH7, Q32PE2, Q32Q92, Q3SZG9, Q3URQ7, Q568P9, Q5E9L5, Q5JTZ9, Q5RCH4, Q5RFR7, Q6NTR1, Q6NZB1, Q7QIL2, Q7TMC8, Q80YU0, Q8HY87, Q8K304, Q8NFF5

Diamond homologs: F4IDS7, P59015, Q8R307, Q9P253, Q24314

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	VPS18	ubiquitination
UBE2D2	“up-regulates activity”	VPS18	binding
VPS18	“down-regulates quantity by destabilization”	PLK2	ubiquitination
VPS18	“form complex”	“HOPS tethering complex”	binding
VPS18	“form complex”	“CORVET tethering complex”	binding
VPS18	“down-regulates activity”	GGA3	monoubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 161 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	6	49.2×	4e-07
endosome to lysosome transport	9	22.1×	2e-07
autophagosome maturation	5	12.8×	4e-03
intracellular protein transport	13	6.2×	5e-05
protein transport	13	4.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	164
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

999 predictions. Top by Δscore:

Variant	Effect	Δscore
15:40895936:A:AG	acceptor_gain	1.0000
15:40895936:AG:A	acceptor_gain	1.0000
15:40895936:AGG:A	acceptor_gain	1.0000
15:40895937:G:GG	acceptor_gain	1.0000
15:40895937:GG:G	acceptor_gain	1.0000
15:40895937:GGG:G	acceptor_gain	1.0000
15:40895937:GGGT:G	acceptor_gain	1.0000
15:40895937:GGGTA:G	acceptor_gain	1.0000
15:40896076:TCCGG:T	donor_loss	1.0000
15:40896077:CCG:C	donor_loss	1.0000
15:40896078:CGG:C	donor_loss	1.0000
15:40896079:GGTAA:G	donor_loss	1.0000
15:40896080:G:GG	donor_gain	1.0000
15:40896081:T:A	donor_loss	1.0000
15:40898904:CAGC:C	acceptor_loss	1.0000
15:40898905:A:AG	acceptor_gain	1.0000
15:40898905:A:AT	acceptor_loss	1.0000
15:40898906:G:GG	acceptor_gain	1.0000
15:40898906:GC:G	acceptor_gain	1.0000
15:40898906:GCAT:G	acceptor_gain	1.0000
15:40898906:GCATT:G	acceptor_gain	1.0000
15:40898994:TACTG:T	donor_gain	1.0000
15:40898996:CTG:C	donor_gain	1.0000
15:40898997:TG:T	donor_gain	1.0000
15:40898997:TGG:T	donor_loss	1.0000
15:40898998:GG:G	donor_gain	1.0000
15:40898999:G:GG	donor_gain	1.0000
15:40899000:T:G	donor_loss	1.0000
15:40901012:CAG:C	donor_loss	1.0000
15:40901014:GGTA:G	donor_loss	1.0000

AlphaMissense

6304 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:40895977:T:C	F44S	0.999
15:40899153:T:C	L112P	0.999
15:40899257:T:A	W147R	0.999
15:40899257:T:C	W147R	0.999
15:40899305:G:T	G163W	0.999
15:40899306:G:A	G163E	0.999
15:40899483:C:A	A222D	0.999
15:40899510:T:C	F231S	0.999
15:40899672:C:A	A285D	0.999
15:40899815:T:C	F333L	0.999
15:40899817:C:A	F333L	0.999
15:40899817:C:G	F333L	0.999
15:40899975:T:A	V386D	0.999
15:40900013:T:A	W399R	0.999
15:40900013:T:C	W399R	0.999
15:40900050:C:A	A411D	0.999
15:40900092:T:A	V425D	0.999
15:40900197:T:C	F460S	0.999
15:40900994:G:C	A726P	0.999
15:40899227:T:A	W137R	0.998
15:40899227:T:C	W137R	0.998
15:40899258:G:C	W147S	0.998
15:40899259:G:C	W147C	0.998
15:40899259:G:T	W147C	0.998
15:40899303:T:A	V162D	0.998
15:40899324:T:A	I169N	0.998
15:40899332:G:C	A172P	0.998
15:40899477:T:A	V220D	0.998
15:40899674:T:A	W286R	0.998
15:40899674:T:C	W286R	0.998

dbSNP variants (sampled 300 via entrez): RS1000466012 (15:40895141 G>C), RS1000854058 (15:40904122 A>G), RS1001466074 (15:40896898 G>A,C), RS1001471293 (15:40901354 C>A,T), RS1001582207 (15:40896466 G>A,T), RS1001885686 (15:40892677 G>A), RS1002074317 (15:40902462 T>C), RS1002468871 (15:40898155 A>G), RS1002510757 (15:40895357 G>A), RS1002551068 (15:40902242 A>G), RS1002583437 (15:40898036 G>A,C,T), RS1003480993 (15:40903757 G>A), RS1003520666 (15:40894069 T>C), RS1003749527 (15:40899742 G>C), RS1003802673 (15:40893327 G>A)

Disease associations

OMIM: gene MIM:608551 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
leukodystrophy	No Known Disease Relationship	Unknown

Mondo (1): leukodystrophy (MONDO:0019046)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001524_12	Visceral adipose tissue/subcutaneous adipose tissue ratio	3.000000e-06
GCST010002_167	Refractive error	3.000000e-11
GCST010725_23	Malaria	2.000000e-06
GCST010725_38	Malaria	3.000000e-06
GCST010725_80	Malaria	7.000000e-06
GCST90002384_376	Hemoglobin	5.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
sodium arsenite	affects expression, increases expression	3
bisphenol S	affects cotreatment, decreases methylation, increases expression	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
urushiol	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
ferrous chloride	decreases expression	1
epigallocatechin gallate	increases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
abrine	increases 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
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Vehicle Emissions	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00889174	Not specified	COMPLETED	The Nosology and Etiology of Leukodystrophies of Unknown Causes
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT02843555	Not specified	COMPLETED	Natural History of the Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT03639285	Not specified	RECRUITING	Natural History, Diagnosis, and Outcomes for Leukodystrophies
NCT05443906	Not specified	RECRUITING	Home Exercise for Individuals with Neurodegenerative Disease