TNFSF15

Summary

TNFSF15 (TNF superfamily member 15, HGNC:11931) is a protein-coding gene on chromosome 9q32, encoding Tumor necrosis factor ligand superfamily member 15 (O95150). Receptor for TNFRSF25 and TNFRSF6B.

The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is abundantly expressed in endothelial cells, but is not expressed in either B or T cells. The expression of this protein is inducible by TNF and IL-1 alpha. This cytokine is a ligand for receptor TNFRSF25 and decoy receptor TNFRSF21/DR6. It can activate NF-kappaB and MAP kinases, and acts as an autocrine factor to induce apoptosis in endothelial cells. This cytokine is also found to inhibit endothelial cell proliferation, and thus may function as an angiogenesis inhibitor. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 9966 — RefSeq curated summary.

At a glance

• GWAS associations: 26
• Clinical variants (ClinVar): 39 total
• Phenotypes (HPO): 41
• MANE Select transcript: NM_005118

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11931
Approved symbol	TNFSF15
Name	TNF superfamily member 15
Location	9q32
Locus type	gene with protein product
Status	Approved
Aliases	TL1, VEGI, TL1A, VEGI192A, MGC129934, MGC129935
Ensembl gene	ENSG00000181634
Ensembl biotype	protein_coding
OMIM	604052
Entrez	9966

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000374044, ENST00000374045

RefSeq mRNA: 2 — MANE Select: NM_005118 NM_001204344, NM_005118

CCDS: CCDS6809

Canonical transcript exons

ENST00000374045 — 4 exons

Exon	Start	End
ENSE00001212368	114792407	114792454
ENSE00001212373	114793526	114793568
ENSE00001462247	114805803	114806039
ENSE00001925927	114784652	114790906

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 90.02.

FANTOM5 (CAGE): breadth broad, TPM avg 18.6405 / max 1638.0897, expressed in 513 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102174	18.4676	492
102175	0.1730	97

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	90.02	gold quality
jejunal mucosa	UBERON:0000399	84.74	gold quality
duodenum	UBERON:0002114	82.31	gold quality
germinal epithelium of ovary	UBERON:0001304	80.29	gold quality
visceral pleura	UBERON:0002401	80.26	gold quality
palpebral conjunctiva	UBERON:0001812	80.08	gold quality
pancreatic ductal cell	CL:0002079	78.57	gold quality
parotid gland	UBERON:0001831	73.46	gold quality
epithelium of nasopharynx	UBERON:0001951	73.37	gold quality
pleura	UBERON:0000977	73.20	gold quality
esophagus squamous epithelium	UBERON:0006920	72.20	gold quality
urethra	UBERON:0000057	71.85	gold quality
ileal mucosa	UBERON:0000331	71.31	silver quality
metanephros cortex	UBERON:0010533	71.15	gold quality
parietal pleura	UBERON:0002400	70.36	gold quality
placenta	UBERON:0001987	70.12	gold quality
epithelial cell of pancreas	CL:0000083	69.77	silver quality
seminal vesicle	UBERON:0000998	69.08	gold quality
epithelium of esophagus	UBERON:0001976	68.90	gold quality
mucosa of paranasal sinus	UBERON:0005030	68.77	gold quality
jejunum	UBERON:0002115	68.69	gold quality
saliva-secreting gland	UBERON:0001044	68.56	gold quality
tibia	UBERON:0000979	68.11	gold quality
islet of Langerhans	UBERON:0000006	67.98	gold quality
prostate gland	UBERON:0002367	67.04	gold quality
minor salivary gland	UBERON:0001830	67.02	gold quality
upper leg skin	UBERON:0004262	66.83	gold quality
oral cavity	UBERON:0000167	66.63	silver quality
rectum	UBERON:0001052	66.57	gold quality
squamous epithelium	UBERON:0006914	66.04	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ENAD-21	yes	628.77
E-ANND-3	yes	5.04

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF6, JUN, LITAF, NFKB1, NFKB, RELA, SP1

miRNA regulators (miRDB)

151 targeting TNFSF15, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-124-3P	99.89	73.74	3043

Literature-anchored findings (GeneRIF, showing 40)

• Vascular endothelial growth inhibitor is an endothelial cell-specific gene and inhibitor of endothelial cell proliferation, angiogenesis, and tumor growth; mediates G1 arrest in G0/G1 cells responding to growth stimuli, and apoptosis in cell division (PMID:11739281)
• TL1A-induced NF-kappaB activation and c-IAP2 production prevent DR3-mediated apoptosis (PMID:12882979)
• TL1A mRNA and protein expression is up-regulated in inflammatory bowel disease, particularly in involved areas of Crohn’s disease (CD) in gut mucosa cell types other than endothelial, including lamina propria lymphocytes as well as tissue macrophages. (PMID:14568967)
• Expression of TL1A and its receptor DR3 by lamina propria mononuclear cells (LPMC) could have significant influence on the severity of mucosal inflammation. (PMID:15207783)
• TL1A and DR3 is involved in atherosclerosis via the induction of pro-inflammatory cytokines/chemokines (PMID:15760679)
• VEGI is an endogenous inhibitor of angiogenesis (PMID:16061878)
• Genetic variations in the TNFSF15 gene contribute to the susceptibility to inflammatory bowel diseases in Japanese and European populations. (PMID:16221758)
• It can be concluded that VEGI72-251 is able to increase the level of human IL-2 production by the activation of T lymphocytes (PMID:16604264)
• a significant association between TNFSF15 and Crohn’s disease (PMID:16966713)
• The induction of TL1A on APCs via specific pathway stimulation suggests a role for TL1A in Th1 responses to pathogens, and in CD. (PMID:17371957)
• Mononuclear phagocytes are a major source of TL1A in rheumatoid arthritis (RA), as revealed by their strong TL1A expression in either synovial fluids or synovial tissue of rheumatoid factor (RF)-seropositive RA patients, but not RF-negative/RA patients. (PMID:17513783)
• TNFSF15 is an ethnic-specific IBD susceptibility gene. Five SNPs that comprise the 2 common haplotypes were genotyped in 599 Caucasian patients with Crohn’s dis, 382 Caucasian patients with ulcerative colitis, and 230 controls. (PMID:17663424)
• TL1A forms a homotrimer with each monomer assuming a jellyroll beta-sandwich fold. The CD loop in TL1A is the longest among the TNF ligand members with known structure and the AA’ loop in TL1A is the second longest after that in TRAIL. (PMID:17935696)
• TL1A may contribute to renal inflammation and injury through DR3-mediated activation of NF-kappaB and caspase-3 (PMID:18287561)
• Variants in TNFSF15 contribute to overall CD susceptibility in European populations, although to a lesser extent than that seen in the Japanese. (PMID:18338776)
• TNFSF15 genotypes play an important role in the pathogenesis of Crohn’s disease in Koreans. (PMID:18422820)
• TL1A may serve as an inflammatory marker in rheumatoid arthritis. Interactions between TL1A and its receptors may be important in the pathogenesis of rheumatois arthritis. (PMID:18757243)
• The allelic expression imbalance of TNFSF15 in peripheral blood mononuclear cells was examined to reveal the effects of the single nucleotide polymorphisms on the transcriptional activity of TNFSF15. (PMID:19124533)
• confirms that TNFSF15 or a closely linked gene is involved in the genetic predisposition to CD (PMID:19174806)
• sodium butyrate has different effects on lung vascular TNFSF15 (TL1A) expression in pulmonary artery and microvascular endothelial cells (PMID:19251437)
• TL1A gene variation exacerbates induction of TL1A in response to FcgammaR stimulation in Jewish CD patients and this may lead to chronic intestinal inflammation via overwhelming T cell responses (PMID:19262684)
• Results provide insights into the structure and function of TL1A and provide the basis for the rational manipulation of its interactions with cognate receptors. (PMID:19522538)
• A haplotype strongly associated with predisposition to spondyloarthritis is located near to TNFSF15. (PMID:19543369)
• these data suggest that TL1A secretion in lymphoid organs might contribute to rheumatoid arthritis initiation by promoting autoantibody production. (PMID:19786547)
• Data suggest that lipopolysaccharide induces TL1A expression through the transcriptional activation via a NF-kappa B pathway. (PMID:19815424)
• Our findings suggest a role for TL1A in pro-inflammatory APC-T cell interactions (PMID:19839006)
• VEGI functions as a negative regulator for aggressiveness during the development and progression of prostate cancer. (PMID:19885571)
• critically involved in the pathogenesis of rheumatoid arthritis (PMID:20125169)
• VEGI functions as a negative regulator of aggressiveness during development and progression of bladder cancer. (PMID:20150621)
• TL1A increased cytotoxicity of IL-12/IL-18-activated NK cells against target cells dependent on NK activation for lysis and could function in vivo as a key co-activator of NK cytotoxicity. (PMID:20349123)
• TL1A promotes foam cell formation in human macrophages in vitro by increasing low density lipoprotein uptake, by enhancing intracellular total and esterified cholesterol levels and reducing cholesterol efflux. (PMID:20410491)
• The TL1A/DcR3 ligand/receptor pair is upregulated in active ulcerative colitis. (PMID:20675196)
• TL1A can regulate the inflammatory processes through modulation of the betaig-h3 expression through two separate pathways, one through PKC and PI3K and the other through ERK, which culminates at NF-kappaB activation. (PMID:20863486)
• role in inflammatory bowel disease pathogenesis (PMID:21153332)
• role of TNFRSF25:TNFSF15 in disease and health (PMID:21153333)
• studies for the first time establish the regulatory axis of AMPK-LITAF-TNFSF15 and also suggest that LITAF may function as a tumor suppressor (PMID:21217782)
• neither TNFSF15 nor IL23R variants contribute to ulcerative colitis susceptibility in Koreans (PMID:21228792)
• Decoy Receptor 3 (DcR3)neutralizes three different TNF ligands: FasL, LIGHT, and TL1A. Crystal structure of DcR3 reported here provides a mechanistic basis for the broadened specificity required to support the decoy function of DcR3. (PMID:21300286)
• Substance P- and hemokinin-1-stimulated monocytes potentiate T helper type (Th)17 cell generation in vitro through IL-1beta, IL-23, and tumor necrosis factor-like (TNF)1A expression. (PMID:21368235)
• DcR3 may act as an inducer, and membrane-bound TL1A may act as a receptor in rheumatoid synovial fibroblasts. (PMID:21537832)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tnfsf15	ENSMUSG00000050395
rattus_norvegicus	Tnfsf15	ENSRNOG00000008930

Paralogs (8): CD40LG (ENSG00000102245), FASLG (ENSG00000117560), TNFSF11 (ENSG00000120659), TNFSF10 (ENSG00000121858), TNFSF14 (ENSG00000125735), LTA (ENSG00000226979), LTB (ENSG00000227507), TNF (ENSG00000232810)

Protein

Protein identifiers

Tumor necrosis factor ligand superfamily member 15 — O95150 (reviewed: O95150)

Alternative names: TNF ligand-related molecule 1, Vascular endothelial cell growth inhibitor

All UniProt accessions (3): A0A0U5JA19, O95150, X6R8I9

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for TNFRSF25 and TNFRSF6B. Mediates activation of NF-kappa-B. Inhibits vascular endothelial growth and angiogenesis (in vitro). Promotes activation of caspases and apoptosis.

Subunit / interactions. Homotrimer.

Subcellular location. Membrane Secreted.

Tissue specificity. Specifically expressed in endothelial cells. Detected in monocytes, placenta, lung, liver, kidney, skeletal muscle, pancreas, spleen, prostate, small intestine and colon.

Induction. Up-regulated by IL1A/interleukin-1 alpha and TNF.

Similarity. Belongs to the tumor necrosis factor family.

Isoforms (3)

UniProt ID	Names	Canonical?
O95150-1	1, TL1A, VEGI-251	yes
O95150-2	2, VEGI-192
O95150-3	3, VEGI-174

RefSeq proteins (2): NP_001191273, NP_005109* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006052	TNF_dom	Domain
IPR006053	TNF	Family
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily

Pfam: PF00229

UniProt features (35 total): strand 15, splice variant 3, site 3, chain 2, glycosylation site 2, topological domain 2, turn 2, disulfide bond 1, sequence variant 1, sequence conflict 1, transmembrane region 1, helix 1, domain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
2RJL	X-RAY DIFFRACTION	2.05
2RE9	X-RAY DIFFRACTION	2.1
2RJK	X-RAY DIFFRACTION	2.3
3K51	X-RAY DIFFRACTION	2.45
2QE3	X-RAY DIFFRACTION	2.5
3MI8	X-RAY DIFFRACTION	2.95
2O0O	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95150-F1	81.64	0.56

Functional residue map

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

Catalytic / active sites (3): 71–72 (cleavage); 187 (important for binding tnfrsf6b); 190 (important for binding tnfrsf6b)

Disulfide bonds (1): 162–202

Glycosylation sites (2): 229, 133

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5669034	TNFs bind their physiological receptors

MSigDB gene sets: 276 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, CREL_01, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_ACTIVATION_OF_NF_KAPPAB_INDUCING_KINASE_ACTIVITY, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, RODRIGUES_NTN1_TARGETS_DN, NFKB_Q6, NFKB_C, IRF7_01, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_APOPTOTIC_SIGNALING_PATHWAY

GO Biological Process (8): immune response (GO:0006955), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), activation of NF-kappaB-inducing kinase activity (GO:0007250), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of extrinsic apoptotic signaling pathway (GO:2001238), cell communication (GO:0007154), signaling (GO:0023052)

GO Molecular Function (4): signaling receptor binding (GO:0005102), cytokine activity (GO:0005125), tumor necrosis factor receptor binding (GO:0005164), protein binding (GO:0005515)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), membrane (GO:0016020), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
TNFR2 non-canonical NF-kB pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
cellular anatomical structure	2
immune system process	1
response to stimulus	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
activation of protein kinase activity	1
non-canonical NF-kappaB signal transduction	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
extrinsic apoptotic signaling pathway	1
positive regulation of apoptotic signaling pathway	1
regulation of extrinsic apoptotic signaling pathway	1
regulation of biological process	1
protein binding	1
receptor ligand activity	1
tumor necrosis factor receptor superfamily binding	1
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1438 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNFSF15	TNFRSF6B	O95407	998
TNFSF15	TNFRSF25	P78507	997
TNFSF15	TNFSF8	P32971	876
TNFSF15	CCDC122	Q5T0U0	779
TNFSF15	TNFRSF21	O75509	766
TNFSF15	NOD2	Q9HC29	759
TNFSF15	TNFRSF14	Q92956	742
TNFSF15	TNFRSF1A	P19438	735
TNFSF15	LACC1	Q8IV20	725
TNFSF15	TNFSF18	Q9UNG2	700
TNFSF15	TNFSF9	P41273	681
TNFSF15	ATG16L1	Q676U5	681
TNFSF15	TNFRSF4	P43489	641
TNFSF15	CD70	P32970	636
TNFSF15	LTBR	P36941	624

IntAct

9 interactions, top by confidence:

A	B	Type	Score
TNFSF15	HTRA2	psi-mi:“MI:0915”(physical association)	0.560
TNFSF15	HTT	psi-mi:“MI:0915”(physical association)	0.560
	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): TNFSF15 (Affinity Capture-MS), TNFSF15 (Affinity Capture-MS), TNFRSF25 (Affinity Capture-Western), TNFRSF6B (Affinity Capture-Western), TNFSF15 (Positive Genetic)

ESM2 similar proteins: A1A5X5, A4IH36, D4AB34, O93449, O95150, O97605, O97626, P04088, P04924, P09529, P10600, P15203, P16047, P17125, P17491, P27093, P36939, P36940, P41047, P42917, P48023, P50591, P50592, P59694, P59695, P63306, P63307, P63308, Q04999, Q07258, Q5UBV8, Q5XIG2, Q6PGN1, Q80WL1, Q861W5, Q8BGU2, Q8BMF8, Q8IUK8, Q8K3Y7, Q8R2Z0

Diamond homologs: O43557, O95150, P04924, P36940, P51435, Q5UBV8, Q861W5, Q8K3Y7, Q9I8D8, Q9QYH9, P09225, P10154, P26445, P36939, P41047, P41155, P48023, P50591, P63306, P63307, P63308, Q06332, Q06600, Q5WR07, Q8JFG3, Q9BDN1, Q9BEA8, Q9XT48, O35734, O77510, O77764, P01374, P01375, P06804, P13296, P16599, P19101, P23383, P23563, P29553

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TNFSF15	up-regulates	TNFRSF25	binding
TNFRSF6B	down-regulates	TNFSF15	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

425 predictions. Top by Δscore:

Variant	Effect	Δscore
9:114790902:CACAA:C	acceptor_gain	1.0000
9:114790903:ACAA:A	acceptor_gain	1.0000
9:114790904:CAA:C	acceptor_gain	1.0000
9:114790904:CAAC:C	acceptor_gain	1.0000
9:114790907:C:CC	acceptor_gain	1.0000
9:114790907:C:CG	acceptor_loss	1.0000
9:114790908:T:A	acceptor_loss	1.0000
9:114792401:GCTTA:G	donor_loss	1.0000
9:114792402:CTTA:C	donor_loss	1.0000
9:114792403:TTA:T	donor_loss	1.0000
9:114792404:TACCT:T	donor_loss	1.0000
9:114792405:ACC:A	donor_loss	1.0000
9:114793524:A:AC	donor_gain	1.0000
9:114793525:C:CC	donor_gain	1.0000
9:114793525:CAAA:C	donor_gain	1.0000
9:114805799:TTACC:T	donor_loss	1.0000
9:114805800:TACC:T	donor_loss	1.0000
9:114805802:C:CG	donor_loss	1.0000
9:114790905:AA:A	acceptor_gain	0.9900
9:114792400:GGCTT:G	donor_loss	0.9900
9:114792452:CATCT:C	acceptor_loss	0.9900
9:114792453:ATCTG:A	acceptor_loss	0.9900
9:114792454:TCTG:T	acceptor_loss	0.9900
9:114792455:C:G	acceptor_loss	0.9900
9:114792456:T:A	acceptor_loss	0.9900
9:114793519:TAC:T	donor_loss	0.9900
9:114793521:C:CG	donor_loss	0.9900
9:114793522:TTAC:T	donor_loss	0.9900
9:114793523:T:TC	donor_loss	0.9900
9:114793524:A:C	donor_loss	0.9900

AlphaMissense

1646 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:114790851:C:A	W119C	0.999
9:114790851:C:G	W119C	0.999
9:114790853:A:G	W119R	0.998
9:114790853:A:T	W119R	0.998
9:114790473:G:C	F245L	0.997
9:114790473:G:T	F245L	0.997
9:114790475:A:G	F245L	0.997
9:114790468:C:T	G247E	0.996
9:114790461:G:C	F249L	0.995
9:114790461:G:T	F249L	0.995
9:114790463:A:G	F249L	0.995
9:114790827:G:C	F127L	0.995
9:114790827:G:T	F127L	0.995
9:114790829:A:G	F127L	0.995
9:114790852:C:G	W119S	0.995
9:114792412:A:G	L99P	0.995
9:114790531:A:G	L226P	0.994
9:114790562:C:G	A216P	0.994
9:114790743:G:C	F155L	0.994
9:114790743:G:T	F155L	0.994
9:114790744:A:G	F155S	0.994
9:114790745:A:G	F155L	0.994
9:114790769:A:C	Y147D	0.994
9:114790466:C:G	A248P	0.993
9:114790515:A:C	S231R	0.993
9:114790515:A:T	S231R	0.993
9:114790517:T:G	S231R	0.993
9:114790465:G:T	A248D	0.992
9:114790469:C:G	G247R	0.992
9:114790469:C:T	G247R	0.992

dbSNP variants (sampled 300 via entrez): RS1000085413 (9:114788000 C>T), RS1000105084 (9:114793350 A>G), RS1000136502 (9:114792998 GTCTATTAGT>G), RS1000313447 (9:114805129 A>C), RS1000470964 (9:114804383 G>A), RS1000656324 (9:114798016 G>C,T), RS1000710422 (9:114804138 C>T), RS1000945511 (9:114785970 G>A,T), RS1000964936 (9:114794317 G>T), RS1000984271 (9:114798295 A>T), RS1001051447 (9:114806561 A>G), RS1001061348 (9:114806878 G>A,C), RS1001114042 (9:114791981 G>A), RS1001159564 (9:114800945 G>T), RS1001331923 (9:114794010 A>G)

Disease associations

OMIM: gene MIM:604052 | disease phenotypes: MIM:609888

GenCC curated gene-disease

Mondo (1): leprosy, susceptibility to, 1 (MONDO:0012358)

Orphanet (1): Leprosy (Orphanet:548)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000820	Abnormality of the thyroid gland
HP:0000939	Osteoporosis
HP:0000952	Jaundice
HP:0000953	Hyperpigmentation of the skin
HP:0000989	Pruritus
HP:0001114	Xanthelasma
HP:0001262	Excessive daytime somnolence
HP:0001278	Orthostatic hypotension
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001399	Hepatic failure
HP:0001402	Hepatocellular carcinoma
HP:0001409	Portal hypertension
HP:0001541	Ascites
HP:0001744	Splenomegaly
HP:0002040	Esophageal varix
HP:0002240	Hepatomegaly
HP:0002360	Sleep disturbance
HP:0002480	Hepatic encephalopathy
HP:0002570	Steatorrhea
HP:0002608	Celiac disease
HP:0002613	Biliary cirrhosis
HP:0002841	Recurrent fungal infections
HP:0002908	Conjugated hyperbilirubinemia
HP:0002960	Autoimmunity
HP:0003073	Hypoalbuminemia
HP:0003119	Abnormal circulating lipid concentration
HP:0003124	Hypercholesterolemia
HP:0003155	Elevated circulating alkaline phosphatase concentration
HP:0003261	Increased circulating IgA concentration

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST000207_5	Crohn’s disease	3.000000e-10
GCST000225_4	Inflammatory bowel disease	3.000000e-08
GCST000546_1	Leprosy	3.000000e-21
GCST000853_10	Ulcerative colitis	1.000000e-06
GCST000879_9	Crohn’s disease	1.000000e-15
GCST000964_9	Ulcerative colitis	6.000000e-12
GCST001118_2	Ulcerative colitis or Crohn’s disease	4.000000e-13
GCST001685_6	Primary biliary cholangitis	3.000000e-14
GCST001725_101	Inflammatory bowel disease	3.000000e-32
GCST001785_11	Crohn’s disease	5.000000e-46
GCST002772_7	Leprosy	9.000000e-42
GCST003097_17	Pediatric autoimmune diseases	1.000000e-08
GCST003360_4	Crohn’s disease	5.000000e-25
GCST003602_12	Inflammatory bowel disease	2.000000e-27
GCST004145_5	Primary biliary cholangitis	8.000000e-19
GCST004302_3	Primary biliary cholangitis	1.000000e-29
GCST005537_173	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	1.000000e-25
GCST007036_4	Primary biliary cholangitis	2.000000e-26
GCST007216_1	Crohn’s disease	3.000000e-26
GCST009391_114	Metabolite levels	1.000000e-06
GCST010042_43	Asthma	3.000000e-09
GCST010043_165	Asthma	5.000000e-08
GCST010577_3	Crohn’s disease	2.000000e-23
GCST011793_8	Early chronic obstructive pulmonary disease in never smokers	4.000000e-06
GCST012073_18	Behcet’s disease	8.000000e-08
GCST012429_2	Asthma (childhood onset)	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0010354	diacylglycerol 36:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	3
Silicon Dioxide	decreases expression, increases expression	3
Tretinoin	increases expression	3
Valproic Acid	increases expression	3
sodium arsenite	decreases expression	2
Cadmium	decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
peracetylated N-azidoacetylmannosamine	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
geldanamycin	decreases expression	1
22-hydroxycholesterol	increases expression	1
2-anisidine	decreases expression	1
propionaldehyde	increases expression	1
25-hydroxycholesterol	increases expression	1
potassium perchlorate	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
perfluorooctanoic acid	increases expression	1
zinc chromate	increases abundance, increases expression	1
nonylphenol	affects reaction, decreases expression, decreases secretion, decreases reaction	1
24,25-epoxycholesterol	increases expression	1
triadimefon	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
usnic acid	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
perfluoro-n-nonanoic acid	increases expression	1
T0901317	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E6S9	Genomeditech CHO-K1 H_TNFSF15(TL1A)	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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