TNFSF14

Summary

TNFSF14 (TNF superfamily member 14, HGNC:11930) is a protein-coding gene on chromosome 19p13.3, encoding Tumor necrosis factor ligand superfamily member 14 (O43557). Cytokine that binds to TNFRSF3/LTBR.

The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF14, which is a member of the tumor necrosis factor receptor superfamily, and which is also known as a herpesvirus entry mediator (HVEM). This protein may function as a costimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus. This protein has been shown to stimulate the proliferation of T cells, and trigger apoptosis of various tumor cells. This protein is also reported to prevent tumor necrosis factor alpha mediated apoptosis in primary hepatocyte. Two alternatively spliced transcript variant encoding distinct isoforms have been reported.

Source: NCBI Gene 8740 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 36 total
• Druggable target: yes
• MANE Select transcript: NM_001376887

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11930
Approved symbol	TNFSF14
Name	TNF superfamily member 14
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	LIGHT, LTg, HVEM-L, CD258
Ensembl gene	ENSG00000125735
Ensembl biotype	protein_coding
OMIM	604520
Entrez	8740

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000245912, ENST00000599359, ENST00000675206, ENST00000850589, ENST00000896417, ENST00000896418

RefSeq mRNA: 3 — MANE Select: NM_001376887 NM_001376887, NM_003807, NM_172014

CCDS: CCDS12171, CCDS45939

Canonical transcript exons

ENST00000675206 — 4 exons

Exon	Start	End
ENSE00000858097	6667113	6667154
ENSE00000858098	6667413	6667449
ENSE00001053513	6661253	6665350
ENSE00004282248	6669851	6670160

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 92.13.

FANTOM5 (CAGE): breadth broad, TPM avg 7.6021 / max 1119.8621, expressed in 404 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178720	2.5153	251
178729	2.2738	257
178718	1.1809	172
178722	0.5441	99
178721	0.3060	77
178728	0.1869	114
178724	0.1330	44
178726	0.1253	43
178717	0.1050	40
178723	0.0981	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	92.13	gold quality
blood	UBERON:0000178	88.32	gold quality
pericardium	UBERON:0002407	87.84	gold quality
parietal pleura	UBERON:0002400	87.16	gold quality
liver	UBERON:0002107	83.76	gold quality
omental fat pad	UBERON:0010414	82.99	gold quality
peritoneum	UBERON:0002358	82.97	gold quality
granulocyte	CL:0000094	82.65	gold quality
pleura	UBERON:0000977	82.37	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.92	gold quality
amniotic fluid	UBERON:0000173	78.43	gold quality
visceral pleura	UBERON:0002401	77.92	gold quality
left uterine tube	UBERON:0001303	76.55	gold quality
buccal mucosa cell	CL:0002336	76.50	silver quality
palpebral conjunctiva	UBERON:0001812	75.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.36	gold quality
leukocyte	CL:0000738	72.80	gold quality
monocyte	CL:0000576	72.26	gold quality
right coronary artery	UBERON:0001625	71.93	gold quality
sperm	CL:0000019	71.74	gold quality
mononuclear cell	CL:0000842	71.73	gold quality
germinal epithelium of ovary	UBERON:0001304	71.06	silver quality
bone marrow	UBERON:0002371	70.80	gold quality
lower esophagus mucosa	UBERON:0035834	70.37	gold quality
male germ cell	CL:0000015	70.02	gold quality
vena cava	UBERON:0004087	69.85	gold quality
lymph node	UBERON:0000029	69.47	gold quality
adipose tissue	UBERON:0001013	68.02	gold quality
vermiform appendix	UBERON:0001154	67.94	gold quality
secondary oocyte	CL:0000655	67.43	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.80
E-HCAD-29	no	3251.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, ETS2, IRF2, NCOA2, NFATC1, NFATC2, NFKB1, NR2C1, NR2C2, RELA, SP1, TP53

Literature-anchored findings (GeneRIF, showing 40)

• Effects in transgenic mice indicate that human LIGHT may function as a major regulator of T cell activation, and implicate LIGHT signaling pathways in inflammation focused on mucosal tissues. (PMID:11714797)
• LIGHT (TNFSF14),5 its membrane-anchored ligand, was also present in atheromatous lesions and highest in regions rich in macrophage-derived foam cells. (PMID:11742858)
• Role of calcium-signaling pathway in the transcriptional control (PMID:12215452)
• LIGHT may act as an anti-apoptotic agent against TNFalpha-mediated liver injury by blocking the activation of both caspase-3 and caspase-8. (PMID:12393901)
• LIGHT, a new member of the TNF superfamily [review] (PMID:12456019)
• Data show that mRNA encoding LIGHT and its receptors [HVEM, LTbetaR, and TR6 (DcR3)] are present in placentas and cytotrophoblast cells at term. (PMID:12466117)
• Soluble LIGHT blocks TR6-Fc costimulated proliferation, lymphokine production, and cytotoxicity of T cells in the presence of T cell receptor ligation. (PMID:12471113)
• LIGHT-sensitized IFN-gamma-mediated apoptosis of MDA-MB-231 cells is probably through down-regulation of anti-apoptosis Bcl-2 family members; it could be caspase (especially caspase-3)-independent, even though extensive caspase activation was observed. (PMID:12767529)
• LIGHT signaling is mediated through both death receptor and mitochondria pathways (PMID:15115612)
• LIGHT-herpesvirus entry mediator mediated signaling as an important immune regulatory mechanism in mucosal inflammatory responses. (PMID:15210782)
• Mechanisms protecting trophoblast cells from LIGHT-mediated apoptosis were studied. (PMID:15215185)
• LIGHT expression by human intestinal T cells suggests the possibility that LIGHT may play a key role in regulation of the mucosal immune system. (PMID:15634882)
• LIGHT protein can be activated on mucosal T cells through a gut-specific CD2-dependent signaling mechanism. (PMID:15634882)
• Data suggest that LIGHT constitutively expressed in human melanoma cells and microvesicles may contribute to regulate T-cell responses to tumor cells. (PMID:15833878)
• NF-kappaB signal plays a key role in LIGHT-mediated upregulation of CD86 expression. (PMID:15895390)
• both LTbetaR and HVEM can discriminatively mediate the expression of different genes in cultured human umbilical vein endothelial cells, including LIGHT, a proinflammatory cytokine (PMID:15917993)
• A transgenic mouse model resembling Crohn’s disease (CD) suggests that up-regulation of LIGHT may be an important mediator of CD pathogenesis. (PMID:15944326)
• LIGHT could serve as a molecular link between lipid metabolism, inflammation, and thrombus formation, which are all features of atherosclerotic plaques. (PMID:16186421)
• platelet-derived LIGHT is biologically active and can induce an inflammatory response in monocytes and particularly within endothelial cells measured as up-regulation of adhesion molecules and release of chemokines (PMID:16861346)
• Blockade of TNFSF14 signaling caused a substantial reduction in the expression of lymphotoxin beta receptor (LTbetaR)-controlled migration factors within the islets and disrupts organization of tertiary structures, leading to prevention of diabetes. (PMID:16934497)
• LIGHT system may regulate early to middle stages of placental development via cell-specific, temporally programmed expression of the ligand and its receptors, and may also assist in preserving placental immune privilege. (PMID:17010447)
• in addition to activating NF-kappaB/p52, LIGHT also activates Stat3 through the NIK pathway (PMID:17543278)
• attenuated Salmonella typhimurium expressing LIGHT inhibited growth of primary tumors, as well as the dissemination of pulmonary metastases, in various mouse tumor models employing murine carcinoma cell lines in immunocompetent mice (PMID:17652173)
• The plasma levels of LIGHT seem to be similar in hemodialysis (HD) patients and healthy subjects and were not affected by gender, age, the mean period of HD history, disease etiology, type of medication and type of using dialysis membrane. (PMID:17826757)
• platelet-associated LIGHT is involved in adhesion of platelets to endothelium while soluble LIGHT induces a pro-inflammatory state in vascular endothelial cells (PMID:17938804)
• Lymphotoxin-beta receptor ligand LIGHT activates both the the noncanonical and classical NF-kappa B pathways leading to proinflammatory gene expression in vascular endothelial cells. (PMID:18292573)
• the allele T of C-770T and the haplotype TTGA of the promoter SNPs in LIGHT gene might decrease the expression of LIGHT and subsequently increase the susceptibility to vascular dementia in females (PMID:18320356)
• derangement of LIGHT may be important for atherogenetic process of ischemic stroke. (PMID:18384455)
• LIGHT was upregulated in both synovial fluid and synovium of rheumatoid arthritis patients compared with osteoarthritis patients. (PMID:18412315)
• These findings suggested that LIGHT might be involved in the progression of inflammatory bone destruction in rheumatoid arthritis. (PMID:19019090)
• LIGHT acts synergistically with PAR-2 activation to promote enhanced release of the proatherogenic interleukin-8 & monocyte chemoattractant protein-1. The interaction between LIGHT & PAR-2 is biologically active, promoting potent inflammatory effects. (PMID:19023130)
• Enhanced plasma levels of soluble LIGHT in patients with chronic infections suggest a role of LIGHT in systemic inflammatory activation. (PMID:19380287)
• unknown killing effect of LIGHT through HVEM on a lymphoid malignancy is described. (PMID:19701890)
• suppresses tumor growth by augmentation of immune response (PMID:19716382)
• mediates organ-specific donor T cells activation in GVHD (PMID:19826934)
• When highly expressed, LIGHT is capable of promoting effector T cell proliferation and differentiation even in a regulatory T (Treg) cell-enriched, suppressive intestinal environment. (PMID:20042587)
• There is over expression of genes related to immune and inflammatory responses, including cytokines such as TNFSF14 in interstitial cystitis (PMID:20096889)
• Increased potential for LIGHT receptor signaling, coupled with increased bioavailability due to lower decoy receptor-3 (DcR3) avidity, provides a mechanism for polymorphic variants in LIGHT to contribute to the pathogenesis of inflammatory diseases. (PMID:20592286)
• These data clearly indicate that ZFP91 is a key regulator in LIGHT-induced activation of non-canonical NF-kappaB pathway in LTbetaR signaling. (PMID:20804734)
• Herpes simplex virus 1 gD interfere HVEM function by competing with its natural ligands and by downregulating HVEM. (PMID:20826693)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tnfsf14	ENSDARG00000111357
mus_musculus	Tnfsf14	ENSMUSG00000005824
rattus_norvegicus	Tnfsf14	ENSRNOG00000047730

Paralogs (8): CD40LG (ENSG00000102245), FASLG (ENSG00000117560), TNFSF11 (ENSG00000120659), TNFSF10 (ENSG00000121858), TNFSF15 (ENSG00000181634), LTA (ENSG00000226979), LTB (ENSG00000227507), TNF (ENSG00000232810)

Protein

Protein identifiers

Tumor necrosis factor ligand superfamily member 14 — O43557 (reviewed: O43557)

Alternative names: Herpes virus entry mediator ligand

All UniProt accessions (1): O43557

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine that binds to TNFRSF3/LTBR. Binding to the decoy receptor TNFRSF6B modulates its effects. Acts as a ligand for TNFRSF14/HVEM. Upon binding to TNFRSF14/HVEM, delivers costimulatory signals to T cells, leading to T cell proliferation and IFNG production.

Subunit / interactions. Homotrimer. Interacts with TNFRSF14.

Subcellular location. Cell membrane Secreted Cytoplasm.

Tissue specificity. Predominantly expressed in the spleen but also found in the brain. Weakly expressed in peripheral lymphoid tissues and in heart, placenta, liver, lung, appendix, and kidney, and no expression seen in fetal tissues, endocrine glands, or nonhematopoietic tumor lines.

Post-translational modifications. N-glycosylated. The soluble form of isoform 1 derives from the membrane form by proteolytic processing.

Induction. Up-regulated after T-cell activation.

Similarity. Belongs to the tumor necrosis factor family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43557-1	1	yes
O43557-2	2, LIGHT delta-TM

RefSeq proteins (3): NP_001363816, NP_003798, NP_742011 (=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 (27 total): strand 12, sequence variant 3, chain 2, topological domain 2, helix 2, transmembrane region 1, domain 1, site 1, glycosylation site 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4KG8	X-RAY DIFFRACTION	2.25
4KGQ	X-RAY DIFFRACTION	2.27
4RSU	X-RAY DIFFRACTION	2.3
4J6G	X-RAY DIFFRACTION	2.4
4EN0	X-RAY DIFFRACTION	2.59
4KGG	X-RAY DIFFRACTION	2.78
7MSG	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43557-F1	84.20	0.62

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 (1): 82–83 (cleavage)

Disulfide bonds (1): 154–187

Glycosylation sites (1): 102

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5668541	TNFR2 non-canonical NF-kB pathway
R-HSA-5669034	TNFs bind their physiological receptors
R-HSA-5676594	TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway

MSigDB gene sets: 363 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_T_CELL_CHEMOTAXIS, GOBP_CELL_CHEMOTAXIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, MODULE_64, GOBP_T_CELL_HOMEOSTASIS, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_MIGRATION, GOBP_LYMPHOCYTE_HOMEOSTASIS, GOBP_LYMPHOCYTE_COSTIMULATION, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION

GO Biological Process (18): apoptotic process (GO:0006915), immune response (GO:0006955), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), T cell chemotaxis (GO:0010818), positive regulation of T cell chemotaxis (GO:0010820), T cell costimulation (GO:0031295), T cell proliferation (GO:0042098), T cell activation (GO:0042110), T cell homeostasis (GO:0043029), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of myoblast differentiation (GO:0045663), cellular response to mechanical stimulus (GO:0071260), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), positive regulation of myoblast fusion (GO:1901741), positive regulation of extrinsic apoptotic signaling pathway (GO:2001238), cell communication (GO:0007154), signaling (GO:0023052)

GO Molecular Function (6): signaling receptor binding (GO:0005102), cytokine activity (GO:0005125), tumor necrosis factor receptor binding (GO:0005164), identical protein binding (GO:0042802), cysteine-type endopeptidase inhibitor activity involved in apoptotic process (GO:0043027), protein binding (GO:0005515)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), plasma membrane (GO:0005886), extracellular region (GO:0005576), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
TNFR2 non-canonical NF-kB pathway	2
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular process	2
positive regulation of intracellular signal transduction	2
protein binding	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
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
lymphocyte chemotaxis	1
T cell migration	1
T cell chemotaxis	1
regulation of T cell chemotaxis	1
positive regulation of lymphocyte chemotaxis	1
positive regulation of T cell migration	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
T cell activation	1
lymphocyte proliferation	1
lymphocyte activation	1
lymphocyte homeostasis	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
myoblast differentiation	1
positive regulation of cell differentiation	1
regulation of myoblast differentiation	1
response to mechanical stimulus	1
cellular response to abiotic stimulus	1
cellular response to external stimulus	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
myoblast fusion	1
positive regulation of syncytium formation by plasma membrane fusion	1
regulation of myoblast fusion	1
extrinsic apoptotic signaling pathway	1

Protein interactions and networks

STRING

1324 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNFSF14	TNFRSF14	Q92956	999
TNFSF14	LTBR	P36941	998
TNFSF14	TNFRSF6B	O95407	951
TNFSF14	ACKR1	Q16570	884
TNFSF14	BTLA	Q7Z6A9	867
TNFSF14	CD160	O95971	802
TNFSF14	TNFSF9	P41273	742
TNFSF14	CD70	P32970	705
TNFSF14	LTA	P01374	704
TNFSF14	TNFRSF9	Q07011	640
TNFSF14	TNFRSF25	P78507	630
TNFSF14	VTCN1	Q7Z7D3	629
TNFSF14	CD27	P26842	621
TNFSF14	TNFRSF4	P43489	616
TNFSF14	CD80	P33681	578

IntAct

77 interactions, top by confidence:

A	B	Type	Score
TNFSF14	TNFRSF14	psi-mi:“MI:0915”(physical association)	0.810
TNFRSF14	TNFSF14	psi-mi:“MI:0915”(physical association)	0.810
TNFSF14	TNFRSF14	psi-mi:“MI:0407”(direct interaction)	0.810
TNFSF14	TMEM11	psi-mi:“MI:0915”(physical association)	0.670
TNFSF14	TMEM11	psi-mi:“MI:0914”(association)	0.670
ZDHHC24	TNFSF14	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	ZDHHC24	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	MAL	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	ADIPOQ	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	SEC23A	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	LHFPL3	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	CXCL9	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	ADAM33	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	BMP10	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	SYS1	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	JAGN1	psi-mi:“MI:0915”(physical association)	0.560
UPK2	TNFSF14	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	OLFM4	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	CLDN11	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	PLLP	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	SEC22A	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	CLDN19	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	PTTG1IP	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	Tnfrsf14	psi-mi:“MI:0915”(physical association)	0.520
TNFSF14	LTBR	psi-mi:“MI:0915”(physical association)	0.520
TNFSF14	Ltbr	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (87): TNFSF14 (Two-hybrid), TNFSF14 (Two-hybrid), TNFSF14 (Two-hybrid), TNFSF14 (Two-hybrid), TNFSF14 (Two-hybrid), TNFSF14 (Two-hybrid), CXCL9 (Two-hybrid), ADAM33 (Two-hybrid), BMP10 (Two-hybrid), CLDN19 (Two-hybrid), JAGN1 (Two-hybrid), MAL (Two-hybrid), TMEM11 (Two-hybrid), ADIPOQ (Two-hybrid), PTTG1IP (Two-hybrid)

ESM2 similar proteins: B6ZK76, B6ZK77, O08722, O08747, O14788, O35235, O43278, O43557, O77764, O95150, O95185, O95390, O97605, O97626, P13296, P27548, P29965, P32971, P32972, P36940, P50592, P51749, P63304, P63305, P79374, Q1G1A2, Q29607, Q5UBV8, Q6QNF3, Q6ZN44, Q761X5, Q7T2Z5, Q8IUK5, Q8IZJ1, Q8JFG3, Q8K1S3, Q8K3Y7, Q91ZV7, Q95MQ5, Q9BDM3

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

1 interactions.

A	Effect	B	Mechanism
TNFSF14	up-regulates	TNFRSF14	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

659 predictions. Top by Δscore:

Variant	Effect	Δscore
19:6665346:GGCCC:G	acceptor_gain	1.0000
19:6665348:CCC:C	acceptor_gain	1.0000
19:6665349:CCC:C	acceptor_gain	1.0000
19:6665350:CCTGT:C	acceptor_gain	1.0000
19:6665351:C:CC	acceptor_gain	1.0000
19:6665351:C:CG	acceptor_loss	1.0000
19:6665354:T:TC	acceptor_gain	1.0000
19:6667410:CA:C	donor_loss	1.0000
19:6665347:GCCC:G	acceptor_gain	0.9900
19:6665348:CCCC:C	acceptor_gain	0.9900
19:6665349:CC:C	acceptor_gain	0.9900
19:6665354:T:C	acceptor_gain	0.9900
19:6667108:CTCAC:C	donor_loss	0.9900
19:6667109:TCA:T	donor_loss	0.9900
19:6667111:A:AT	donor_loss	0.9900
19:6667153:CT:C	acceptor_gain	0.9900
19:6667154:TCTG:T	acceptor_loss	0.9900
19:6667155:C:CC	acceptor_gain	0.9900
19:6667155:C:G	acceptor_gain	0.9900
19:6667155:CTGG:C	acceptor_loss	0.9900
19:6667156:T:A	acceptor_loss	0.9900
19:6667411:A:AC	donor_gain	0.9900
19:6667412:C:CC	donor_gain	0.9900
19:6667445:CCGTC:C	acceptor_gain	0.9900
19:6667446:CGTC:C	acceptor_gain	0.9900
19:6667446:CGTCC:C	acceptor_gain	0.9900
19:6667450:C:CA	acceptor_loss	0.9900
19:6667451:T:A	acceptor_loss	0.9900
19:6669849:A:AC	donor_gain	0.9900
19:6669850:C:CC	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000287634 (19:6668514 T>G), RS1000416241 (19:6661795 A>G), RS1000489886 (19:6662014 G>C), RS1000528303 (19:6672333 G>A), RS1000855338 (19:6666552 C>T), RS1000860689 (19:6660983 G>A), RS1000968672 (19:6665527 G>A), RS1001096859 (19:6671582 G>A), RS1001562310 (19:6669559 C>T), RS1001973987 (19:6664175 G>A,T), RS1002947960 (19:6662369 G>C), RS1002978979 (19:6662571 A>G), RS1003245940 (19:6668838 G>A), RS1003291500 (19:6670216 C>A,T), RS1003838568 (19:6664852 G>A,C,T)

Disease associations

OMIM: gene MIM:604520 | 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
GCST001198_39	Multiple sclerosis	9.000000e-14
GCST004608_131	Granulocyte percentage of myeloid white cells	8.000000e-10
GCST004609_93	Monocyte percentage of white cells	5.000000e-11
GCST005531_65	Multiple sclerosis	2.000000e-24
GCST005977_18	Monocyte count	7.000000e-11
GCST006585_2447	Blood protein levels	4.000000e-08
GCST009597_292	Multiple sclerosis	8.000000e-33
GCST009731_65	Blood protein levels in cardiovascular risk	1.000000e-31

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0010613	tumor necrosis factor ligand superfamily member 14 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712914 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression, decreases expression, affects cotreatment	3
Cyclosporine	decreases expression	3
Cisplatin	increases expression	2
Estradiol	affects cotreatment, decreases expression, affects expression, increases reaction	2
Lipopolysaccharides	affects cotreatment, increases expression, decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bisphenol F	increases methylation	1
propionaldehyde	increases expression	1
lead acetate	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	affects expression	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	decreases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
PCB 180	affects expression	1
pinostrobin	increases expression	1
lipopolysaccharide, E. coli O26-B6	decreases expression	1
beta-hydroxy simvastatin acid	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A9P5	LIGHT-CHO	Spontaneously immortalized cell line	Female
CVCL_E6S8	Genomeditech CHO-K1 H_TNFSF14(LIGHT)	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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