IFI30

Summary

IFI30 (IFI30 lysosomal thiol reductase, HGNC:5398) is a protein-coding gene on chromosome 19p13.11, encoding Gamma-interferon-inducible lysosomal thiol reductase (P13284). Lysosomal thiol reductase that catalyzes protein disulfide bonds reduction.

The protein encoded by this gene is a lysosomal thiol reductase that at low pH can reduce protein disulfide bonds. The enzyme is expressed constitutively in antigen-presenting cells and induced by gamma-interferon in other cell types. This enzyme has an important role in MHC class II-restricted antigen processing.

Source: NCBI Gene 10437 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_006332

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5398
Approved symbol	IFI30
Name	IFI30 lysosomal thiol reductase
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	IFI-30, GILT, IP30, MGC32056, IP-30
Ensembl gene	ENSG00000216490
Ensembl biotype	protein_coding
OMIM	604664
Entrez	10437

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000407280, ENST00000597802, ENST00000600463, ENST00000873894, ENST00000971116, ENST00000971117

RefSeq mRNA: 1 — MANE Select: NM_006332 NM_006332

CCDS: CCDS46015

Canonical transcript exons

ENST00000407280 — 7 exons

Exon	Start	End
ENSE00000871115	18173813	18173973
ENSE00003471545	18175605	18175697
ENSE00003475429	18175311	18175385
ENSE00003491247	18177140	18177292
ENSE00003617948	18177711	18177764
ENSE00003631009	18177849	18178117
ENSE00003789823	18175040	18175222

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 99.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 434.9629 / max 16521.5160, expressed in 1800 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174604	432.1368	1799
174606	1.3556	261
174605	0.5763	210
174619	0.4975	147
174603	0.3025	151
174607	0.0942	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.85	gold quality
leukocyte	CL:0000738	99.83	gold quality
granulocyte	CL:0000094	99.72	gold quality
blood	UBERON:0000178	99.61	gold quality
vermiform appendix	UBERON:0001154	99.58	gold quality
spleen	UBERON:0002106	99.33	gold quality
upper lobe of left lung	UBERON:0008952	99.30	gold quality
right lung	UBERON:0002167	99.26	gold quality
lymph node	UBERON:0000029	99.21	gold quality
duodenum	UBERON:0002114	98.74	gold quality
right adrenal gland cortex	UBERON:0035827	98.39	gold quality
left adrenal gland cortex	UBERON:0035825	98.24	gold quality
left adrenal gland	UBERON:0001234	98.23	gold quality
placenta	UBERON:0001987	98.21	gold quality
gall bladder	UBERON:0002110	98.19	gold quality
right adrenal gland	UBERON:0001233	98.05	gold quality
bone marrow	UBERON:0002371	97.67	gold quality
rectum	UBERON:0001052	97.62	gold quality
bone marrow cell	CL:0002092	97.13	gold quality
adrenal gland	UBERON:0002369	96.93	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.67	gold quality
right coronary artery	UBERON:0001625	96.56	gold quality
lung	UBERON:0002048	96.41	gold quality
omental fat pad	UBERON:0010414	96.39	gold quality
body of stomach	UBERON:0001161	96.38	gold quality
adult mammalian kidney	UBERON:0000082	96.32	gold quality
adipose tissue	UBERON:0001013	96.06	gold quality
mucosa of transverse colon	UBERON:0004991	95.90	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.87	gold quality
mucosa of stomach	UBERON:0001199	95.44	gold quality

Single-cell (SCXA)

Detected in 51 experiment(s), a significant marker in 48.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	6406.42
E-MTAB-8498	yes	4698.67
E-GEOD-75688	yes	4414.69
E-MTAB-9841	yes	4006.38
E-CURD-120	yes	3843.44
E-GEOD-135922	yes	3700.75
E-MTAB-6678	yes	3667.58
E-CURD-126	yes	3600.46
E-MTAB-6653	yes	3472.58
E-MTAB-6308	yes	3254.38
E-MTAB-7407	yes	3203.26
E-MTAB-10885	yes	3147.06
E-MTAB-8322	yes	3094.56
E-MTAB-6701	yes	3067.45
E-MTAB-9221	yes	3054.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

25 targeting IFI30, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-6871-3P	99.43	68.85	741
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-374B-3P	98.63	68.24	1360
HSA-MIR-3158-3P	98.45	64.25	560
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-585-5P	97.54	69.02	955
HSA-MIR-27A-5P	97.01	65.63	528
HSA-MIR-383-5P	96.86	67.55	820
HSA-MIR-12115	94.19	66.37	738
HSA-MIR-1298-3P	94.05	64.84	620

Literature-anchored findings (GeneRIF, showing 21)

• Absence of gamma-interferon-inducible lysosomal thiol reductase in melanomas disrupts T cell recognition of select immunodominant epitopes. (PMID:12021307)
• Role of the C-terminal propeptide in the activity and maturation of gamma -interferon-inducible lysosomal thiol reductase (GILT). (PMID:12198183)
• GILT-expressing melanoma cells could prove to be very promising for direct antigen presentation and CD4+ T cell recognition (PMID:18343923)
• studied gene expression profile of brain lesions of a patient with Neuromyelitis optica by using DNA microarray; found marked up-regulation of interferon gamma-inducible protein 30 (IFI30), CD163, and secreted phosphoprotein 1 (SPP1, osteopontin) (PMID:18410276)
• GILT is required for efficient histocompatiblity class II-restricted processing of melanoma antigen tyrosinase-related protein 1 epitope in vitro and accelerates the onset of vitiligo in TRP1-specific T-cell receptor transgenic mice. (PMID:20668223)
• Single nucleotide polymorphism of the interferon-gamma-inducible protein 30 gene is associated with hyperglycemia in severely obese individuals. (PMID:21701784)
• this review discusses recent studies that have advanced our understanding of the role of GILT in antigen processing and revealed surprising new functions for the enzyme.[review] (PMID:23246037)
• The lysosomal thiol reductase GILT expressed by antigen-presenting cells has diverse cellular and organismal functions. (Review) (PMID:26116226)
• GILT expression is anticipated to result in improved presentation of melanoma antigens and more effective antimelanoma T-cell responses. (PMID:26930048)
• GILT functions as a host restriction factor against the retroviruses. (PMID:27655726)
• Results shows that GILT expression is required for downregulation of PAX-3 proteins in late stage human melanoma cells. GILT co-localizes with PAX-3 proteins regulating its expression through the autophagy and lysosomal degradation pathway in human melanoma cells. (PMID:28857256)
• GILT was highly expressed as observed in the public database on human gliomas and two human glioma cell lines, U373MG and U87MG cells. The downregulation of GILT by lentiviral-mediated silencing inhibits the cell growth, colony formation, and migration but promotes apoptosis and results in cell cycle arrest at the G0/G1 phase in the U373MG cells. (PMID:30587343)
• GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function. (PMID:31631785)
• IFI30 expression is an independent unfavourable prognostic factor in glioma. (PMID:32969157)
• IFI30 expression predicts patient prognosis in breast cancer and dictates breast cancer cells proliferation via regulating autophagy. (PMID:34400904)
• Prognostic value of gamma-interferon-inducible lysosomal thiol reductase expression in female patients diagnosed with breast cancer. (PMID:34648659)
• IDO1, FAT10, IFI6, and GILT Are Involved in the Antiretroviral Activity of gamma-Interferon and IDO1 Restricts Retrovirus Infection by Autophagy Enhancement. (PMID:35883685)
• Interferon-gamma inducible protein 30 promotes the epithelial-mesenchymal transition-like phenotype and chemoresistance by activating EGFR/AKT/GSK3beta/beta-catenin pathway in glioma. (PMID:37408388)
• Comprehensive analysis of the role of interferon gamma-inducible protein 30 on immune infiltration and prognosis in clear cell renal cell carcinoma. (PMID:37991414)
• A Transcription Factor ZNF384, Regulated by LINC00265, Activates the Expression of IFI30 to Stimulate Malignant Progression in Glioma. (PMID:38141017)
• [Knockdown of interferon-gamma inducible protein 30 (IFI30) inhibits the proliferation, invasion and migration of human glioma U251 cells by activating STAT1 and promotes their apoptosis]. (PMID:38246175)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ifi30	ENSMUSG00000031838
rattus_norvegicus	Ifi30	ENSRNOG00000019387
drosophila_melanogaster	CG41378	FBGN0085638
caenorhabditis_elegans		WBGENE00015336

Protein

Protein identifiers

Gamma-interferon-inducible lysosomal thiol reductase — P13284 (reviewed: P13284)

Alternative names: Gamma-interferon-inducible protein IP-30, Legumaturain

All UniProt accessions (2): M0QZG3, P13284

UniProt curated annotations — full annotation on UniProt →

Function. Lysosomal thiol reductase that catalyzes protein disulfide bonds reduction. Plays an important role in antigen processing and presentation, of namely both major histocompatibility complex (MHC) class I- and class II-restricted antigen by reducing the disulfide bonds of endocytosed proteins and facilitating their unfolding and optimal degradation. Shares with thioredoxin a reduction mechanism in which the N-terminal cysteine thiol group in the CXXC active site motif initiates a nucleophilic attack on the substrate disulfide bond,resulting in the formation of a mixed disulfide-linked enzyme-substrate intermediate. Subsequent intramolecular attack by the second cysteine thiol group enables the release of the reduced substrate and oxidized enzyme. Lysosomal cysteine is a physiological reducing agent that is capable of reducing IFI30, so that it can catalyzes the next reaction. Dithiothreitol, cysteine, and cysteinyl glycine, but not glutathione, are capable of regenerating active precursor and mature IFI30 in vitro.

Subunit / interactions. Dimer; disulfide-linked.

Subcellular location. Secreted. Lysosome.

Tissue specificity. Expressed constitutively in antigen-presenting cells.

Post-translational modifications. N-glycosylated. Sugar chains contain mannose-6-phosphate. Synthesized as a 35 kDa precursor which is then processed into the mature 30 kDa form via cleavage of N-terminal and C-terminal propeptides. Processing of the precursor is mediated by multiple lysosomal proteases.

Induction. Induced by IFN-gamma in other cell types.

Miscellaneous. Both precursor form and mature form have thiol reductase activity.

Similarity. Belongs to the GILT family.

RefSeq proteins (1): NP_006323* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004911	Interferon-induced_GILT	Family

Pfam: PF03227

Catalyzed reactions (Rhea), 2 shown:

• [protein]-disulfide + 2 L-cysteine = [protein]-dithiol + L-cystine (RHEA:86267)
• 2 L-cysteinylglycine + [protein]-disulfide = L-cystine-bis-glycine + [protein]-dithiol (RHEA:86315)

UniProt features (19 total): disulfide bond 5, sequence conflict 5, glycosylation site 3, propeptide 2, mutagenesis site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13284-F1	83.71	0.72

Functional residue map

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

Disulfide bonds (5): 148–162, 226–237, 72–75, 117–124, 132–178

Glycosylation sites (3): 63, 95, 108

Mutagenesis-validated functional residues (2):

Position	Phenotype
72	abolishes reducing activity, does not affect dimerization. abolishes reducing activity; when associated with s-75.
75	abolishes reducing activity, does not affect dimerization. abolishes reducing activity; when associated with s-72.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2132295	MHC class II antigen presentation
R-HSA-877300	Interferon gamma signaling

MSigDB gene sets: 400 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, MCLACHLAN_DENTAL_CARIES_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MODULE_128

GO Biological Process (5): antigen processing and presentation of exogenous peptide antigen via MHC class II (GO:0019886), antigen processing and presentation of exogenous peptide antigen via MHC class I (GO:0042590), negative regulation of fibroblast proliferation (GO:0048147), protein stabilization (GO:0050821), immune system process (GO:0002376)

GO Molecular Function (4): oxidoreductase activity, acting on a sulfur group of donors (GO:0016667), oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor (GO:0016671), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (5): extracellular region (GO:0005576), lysosome (GO:0005764), cytosol (GO:0005829), cell junction (GO:0030054), lysosomal lumen (GO:0043202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
antigen processing and presentation of exogenous peptide antigen	2
antigen processing and presentation of peptide antigen via MHC class II	1
antigen processing and presentation of peptide antigen via MHC class I	1
negative regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
regulation of protein stability	1
biological_process	1
oxidoreductase activity	1
oxidoreductase activity, acting on a sulfur group of donors	1
binding	1
catalytic activity	1
lytic vacuole	1
cytoplasm	1
lysosome	1
vacuolar lumen	1

Protein interactions and networks

STRING

2227 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFI30	GYPC	P04921	730
IFI30	TXN	P10599	687
IFI30	HLA-DMA	P28067	571
IFI30	CD8A	P01732	565
IFI30	LGMN	Q99538	537
IFI30	IFI35	P80217	523
IFI30	CTSS	P25774	520
IFI30	CIITA	P33076	512
IFI30	DKK3	Q9UBP4	497
IFI30	IFI27L1	Q96BM0	482
IFI30	CD74	P04233	481
IFI30	MYC	P01106	468
IFI30	IFITM1	P13164	464
IFI30	DNAJB11	Q9UBS4	462
IFI30	FOSL1	P15407	455

IntAct

52 interactions, top by confidence:

A	B	Type	Score
IFI30	DAPK1	psi-mi:“MI:0914”(association)	0.730
NOTCH2NLA	IFI30	psi-mi:“MI:0915”(physical association)	0.560
IFI30	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.560
IFI30	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-12	IFI30	psi-mi:“MI:0915”(physical association)	0.560
IFI30	TGM1	psi-mi:“MI:0915”(physical association)	0.560
DAPK1	MYO1B	psi-mi:“MI:0914”(association)	0.530
IFI30	PRC1	psi-mi:“MI:0914”(association)	0.530
CDRT15	CDRT15L2	psi-mi:“MI:0914”(association)	0.530
GFOD1	PER1	psi-mi:“MI:0914”(association)	0.530
ARL4D	IFI30	psi-mi:“MI:0914”(association)	0.530
DEFB104A	IFI30	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
SPG11	IFI30	psi-mi:“MI:0915”(physical association)	0.370
Cnot2	CNOT1	psi-mi:“MI:0914”(association)	0.350
KIFAP3	TAF4	psi-mi:“MI:0914”(association)	0.350
Septin6	SEPTIN10	psi-mi:“MI:0914”(association)	0.350
NEU4	AIP	psi-mi:“MI:0914”(association)	0.350
PLB1	WDR47	psi-mi:“MI:0914”(association)	0.350
DEFB104A	HRAS	psi-mi:“MI:0914”(association)	0.350
ARL4D		psi-mi:“MI:0914”(association)	0.350
cfp6	IPO5	psi-mi:“MI:0914”(association)	0.350
DAPK1	MYO1C	psi-mi:“MI:0914”(association)	0.350
rl10_rl10l_human	ANKRD28	psi-mi:“MI:0914”(association)	0.350
GOLGA8G	GOLGA8J	psi-mi:“MI:0914”(association)	0.350
DEFB136	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (124): KRTAP4-12 (Two-hybrid), NOTCH2NL (Two-hybrid), IFI30 (Affinity Capture-MS), IFI30 (Affinity Capture-MS), IFI30 (Affinity Capture-MS), TJP1 (Affinity Capture-MS), FAM120A (Affinity Capture-MS), LLGL2 (Affinity Capture-MS), DAPK1 (Affinity Capture-MS), TTC31 (Affinity Capture-MS), MKLN1 (Affinity Capture-MS), ELP3 (Affinity Capture-MS), DEPDC1B (Affinity Capture-MS), UBE3B (Affinity Capture-MS), MRPS7 (Affinity Capture-MS)

ESM2 similar proteins: A0JPF9, A2VE29, A6QPN6, A8T658, B3SP85, E7E2N8, F1QVU0, H2N4I1, O00391, O08841, O95479, P06802, P07911, P13284, P20062, P23276, P48733, P55104, P56201, P59996, Q13219, Q16549, Q499T2, Q4R7M2, Q5R5C1, Q5REL7, Q5RER0, Q5RJG7, Q5U2X4, Q5XWD5, Q62849, Q6IUU3, Q6P6S4, Q80W65, Q86UX2, Q8BND5, Q8CFX1, Q8NCG5, Q92179, Q924C3

Diamond homologs: A6QPN6, B3SP85, E7E2N8, O17861, P13284, Q499T2, Q5XJN2, Q9ESY9, Q9SV73, Q9VCK1, Q7PQD1, Q9VCK2, P34276

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IFI30	“up-regulates quantity”	“peptide antigen”	“chemical modification”
IFI30	“down-regulates quantity”	oligopeptide	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1028 predictions. Top by Δscore:

Variant	Effect	Δscore
19:18173974:GT:G	donor_loss	1.0000
19:18173974:GTA:G	donor_loss	1.0000
19:18173975:T:A	donor_loss	1.0000
19:18175222:GG:G	donor_loss	1.0000
19:18175223:G:C	donor_loss	1.0000
19:18175381:TGGAG:T	donor_loss	1.0000
19:18175383:GAGGT:G	donor_loss	1.0000
19:18175384:AG:A	donor_loss	1.0000
19:18175385:GG:G	donor_loss	1.0000
19:18175385:GGTGA:G	donor_loss	1.0000
19:18175386:G:GA	donor_loss	1.0000
19:18175387:T:G	donor_loss	1.0000
19:18175596:A:AG	acceptor_gain	1.0000
19:18175597:A:G	acceptor_gain	1.0000
19:18175600:CCCA:C	acceptor_loss	1.0000
19:18175601:CCA:C	acceptor_loss	1.0000
19:18175602:CAG:C	acceptor_loss	1.0000
19:18175602:CAGGC:C	acceptor_loss	1.0000
19:18175603:A:AG	acceptor_gain	1.0000
19:18175603:A:AT	acceptor_loss	1.0000
19:18175603:AG:A	acceptor_gain	1.0000
19:18175603:AGGCC:A	acceptor_loss	1.0000
19:18175604:G:A	acceptor_loss	1.0000
19:18175604:G:GA	acceptor_gain	1.0000
19:18175604:GG:G	acceptor_gain	1.0000
19:18175604:GGC:G	acceptor_gain	1.0000
19:18175604:GGCC:G	acceptor_gain	1.0000
19:18175604:GGCCT:G	acceptor_gain	1.0000
19:18175694:ACTA:A	donor_gain	1.0000
19:18175695:CTA:C	donor_gain	1.0000

AlphaMissense

1620 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:18177230:G:C	A192P	0.996
19:18175334:G:C	W113C	0.995
19:18175334:G:T	W113C	0.995
19:18175338:T:C	F115L	0.994
19:18175340:C:A	F115L	0.994
19:18175340:C:G	F115L	0.994
19:18175344:T:A	C117S	0.994
19:18175345:G:C	C117S	0.994
19:18177277:G:C	W207C	0.994
19:18177277:G:T	W207C	0.994
19:18175212:G:T	G102V	0.993
19:18175365:T:A	C124S	0.993
19:18175366:G:C	C124S	0.993
19:18175608:T:A	C132S	0.993
19:18175609:G:C	C132S	0.993
19:18177188:T:A	C178S	0.993
19:18177189:G:C	C178S	0.993
19:18177750:T:A	C226S	0.993
19:18177751:G:C	C226S	0.993
19:18175339:T:G	F115C	0.992
19:18175609:G:A	C132Y	0.992
19:18175344:T:C	C117R	0.991
19:18175610:C:G	C132W	0.991
19:18177216:T:C	L187P	0.991
19:18175339:T:C	F115S	0.990
19:18175131:G:A	C75Y	0.989
19:18175132:C:G	C75W	0.989
19:18175206:C:A	P100H	0.989
19:18175608:T:C	C132R	0.989
19:18175346:C:G	C117W	0.988

dbSNP variants (sampled 300 via entrez): RS1000028829 (19:18175106 T>C), RS1001072455 (19:18174100 G>C,T), RS1001423445 (19:18175900 T>C,G), RS1001838530 (19:18172489 C>T), RS1001978587 (19:18173847 C>G,T), RS1002885178 (19:18172145 C>G,T), RS1003082359 (19:18177156 C>T), RS1004370819 (19:18174518 G>C,T), RS1004908471 (19:18173698 G>A), RS1005333494 (19:18177067 C>A,T), RS1005964995 (19:18175937 G>A,C,T), RS1006144344 (19:18173719 C>A,T), RS1006609700 (19:18174827 G>A,C), RS1007090266 (19:18176612 G>T), RS1008246131 (19:18172929 A>G)

Disease associations

OMIM: gene MIM:604664 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST005531_67	Multiple sclerosis	2.000000e-24
GCST007483_40	Waist-to-hip ratio adjusted for BMI (additive genetic model)	3.000000e-10
GCST007487_23	Waist-to-hip ratio adjusted for BMI (additive genetic model)	6.000000e-10
GCST007500_6	Waist-to-hip ratio adjusted for BMI (additive genetic model)	4.000000e-11
GCST007502_20	Waist-to-hip ratio adjusted for BMI (additive genetic model)	2.000000e-11
GCST008550_34	Mental health study participation (completed survey)	2.000000e-09
GCST009597_37	Multiple sclerosis	6.000000e-25
GCST90011900_160	Serum alkaline phosphatase levels	1.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0010130	health study participation
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, affects cotreatment, increases expression	10
Benzo(a)pyrene	decreases reaction, increases expression, increases methylation	5
Cisplatin	increases expression, affects response to substance, affects cotreatment	3
Cyclosporine	decreases expression	3
bisphenol A	increases expression, increases methylation	2
sodium arsenite	affects expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
chlorophyllin	decreases reaction, increases expression	1
testosterone undecanoate	increases expression	1
trichostatin A	affects expression	1
sodium bichromate	decreases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
nickel sulfate	increases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1

Clinical trials (associated diseases)

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