TNFRSF12A

Summary

TNFRSF12A (TNF receptor superfamily member 12A, HGNC:18152) is a protein-coding gene on chromosome 16p13.3, encoding Tumor necrosis factor receptor superfamily member 12A (Q9NP84). Receptor for TNFSF12/TWEAK.

Involved in positive regulation of extrinsic apoptotic signaling pathway and regulation of wound healing. Predicted to be located in cell surface and ruffle. Predicted to be active in plasma membrane.

Source: NCBI Gene 51330 — RefSeq curated summary.

At a glance

• Druggable target: yes
• MANE Select transcript: NM_016639

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18152
Approved symbol	TNFRSF12A
Name	TNF receptor superfamily member 12A
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FN14, TweakR, CD266
Ensembl gene	ENSG00000006327
Ensembl biotype	protein_coding
OMIM	605914
Entrez	51330

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000326577, ENST00000341627, ENST00000571351, ENST00000573001, ENST00000574699, ENST00000575124, ENST00000575836, ENST00000917163, ENST00000917164, ENST00000917165

RefSeq mRNA: 1 — MANE Select: NM_016639 NM_016639

CCDS: CCDS10489

Canonical transcript exons

ENST00000326577 — 4 exons

Exon	Start	End
ENSE00003539984	3021555	3021689
ENSE00003665681	3021215	3021319
ENSE00003899196	3021771	3022383
ENSE00003901828	3020368	3020491

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 97.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 189.4314 / max 1652.4013, expressed in 1784 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152361	178.5126	1780
152360	6.1202	1279
152362	4.7641	1090
152359	0.0344	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.61	gold quality
ascending aorta	UBERON:0001496	96.84	gold quality
thoracic aorta	UBERON:0001515	96.72	gold quality
metanephros cortex	UBERON:0010533	96.34	gold quality
body of pancreas	UBERON:0001150	95.84	gold quality
type B pancreatic cell	CL:0000169	95.41	gold quality
adenohypophysis	UBERON:0002196	95.22	gold quality
gall bladder	UBERON:0002110	94.75	gold quality
right coronary artery	UBERON:0001625	94.66	gold quality
upper lobe of left lung	UBERON:0008952	94.37	gold quality
islet of Langerhans	UBERON:0000006	94.34	gold quality
pancreas	UBERON:0001264	94.29	gold quality
heart left ventricle	UBERON:0002084	93.94	gold quality
cardiac ventricle	UBERON:0002082	93.79	gold quality
descending thoracic aorta	UBERON:0002345	93.75	gold quality
upper lobe of lung	UBERON:0008948	93.57	gold quality
aorta	UBERON:0000947	93.40	gold quality
left coronary artery	UBERON:0001626	93.34	gold quality
pituitary gland	UBERON:0000007	92.90	gold quality
coronary artery	UBERON:0001621	92.73	gold quality
left ventricle myocardium	UBERON:0006566	92.64	gold quality
heart right ventricle	UBERON:0002080	92.37	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.37	gold quality
cartilage tissue	UBERON:0002418	92.05	gold quality
heart	UBERON:0000948	91.90	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.37	gold quality
left uterine tube	UBERON:0001303	91.34	gold quality
right atrium auricular region	UBERON:0006631	91.09	gold quality
left adrenal gland	UBERON:0001234	91.08	gold quality
popliteal artery	UBERON:0002250	90.96	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	1918.20
E-HCAD-13	yes	1086.72
E-MTAB-9154	yes	814.36
E-MTAB-10662	yes	761.56
E-GEOD-130473	yes	708.42
E-MTAB-8221	yes	547.25
E-MTAB-8142	yes	97.87
E-MTAB-8410	yes	35.84
E-MTAB-10553	yes	27.06
E-HCAD-10	yes	24.56
E-HCAD-9	yes	7.97
E-GEOD-130148	yes	6.81
E-MTAB-6678	yes	6.24
E-MTAB-7052	no	1047.35
E-CURD-10	no	234.88

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNMT3A, F2R, F2RL1, HR, MAML1, NFATC2, NR1I2, RARA

miRNA regulators (miRDB)

41 targeting TNFRSF12A, 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-4481	100.00	66.42	1669
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-1301-5P	98.09	66.62	495
HSA-MIR-6502-5P	98.09	66.73	495
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-8057	97.64	66.54	897
HSA-MIR-4287	97.55	67.24	1247
HSA-MIR-4685-3P	97.55	67.35	1255
HSA-MIR-4640-5P	97.42	66.33	1543

Literature-anchored findings (GeneRIF, showing 40)

• These results indicated that TWEAK could induce pro-inflammatory reactions via fibroblast growth factor-inducible 14 (Fn14)on human umbilical vein endothelial cells. (PMID:12445828)
• FN14 is the sole mediator of the multiple pathways of TWEAK-induced cell death in all TWEAK-sensitive tumor cell lines. (PMID:12496418)
• up-regulated in migrating glioma cells in vitro and overexpressed in advanced glial tumors (PMID:12651623)
• TWEAK acts on human keratinocytes as an inducer of RANTES via Fn14. (PMID:15140220)
• TWEAK/TWEAK receptor interactions have roles in the pathogenesis of inflammatory and systemic autoimmune diseases [review] (PMID:15353286)
• Fn14 protein functions, in part, through the NFkappaB signaling pathway to up-regulate BCL-XL and BCL-W expression to foster malignant glioblastoma cell survival. (PMID:15611130)
• Expression of Fn14 in subcutaneous adipose tissue from obese patients. (PMID:16503147)
• the TWEAK-Fn14 interaction is highly dependent on multiple Fn14 residues located in both CRD modules (PMID:16526941)
• TWEAK and Fn14 are expressed in atherosclerotic plaques and could be novel mediators of atherosclerosis. (PMID:16809572)
• The Fn14 promoter has NF-kappaB binding sites mediating positive feedback causing sustained overexpression of Fn14 & enduring glioma cell invasion. The Fn14 cascade operates as a positive feedback mechanism for elevated & sustained Fn14 expression. (PMID:17018610)
• These results indicate that the TWEAK/Fn14 pathway is a novel regulator of skeletal muscle precursor cells and illustrate an important mechanism by which inflammatory cytokines influence tissue regeneration and repair. (PMID:17124496)
• Fn14 receptor is required for the expression of myogenic regulatory factors and differentiation of myoblasts into myotubes. (PMID:17383968)
• Fn14 protein expression increased with disease progression in esophageal adenocarcinoma (PMID:17594693)
• Fn14-mediated NF-kappaB pathway activation has a role in in breast tumor invasion and metastasis (PMID:18505918)
• Taken together, these findings indicate that the TWEAK/Fn14 pathway contributes to inflammation and tissue injury and is, therefore, a potential therapeutic target in MS. (PMID:19018248)
• determination of the solution structure of the Fn14 cysteine-rich domain (CRD)(Glu28-Ala70) by heteronuclear NMR (PMID:19241374)
• Human cardiomyocytes express the TWEAK receptor Fn14. TWEAK/Fn14 may be important in regulating myocardial structural remodeling and function and may play a role in the pathogenesis of dilated cardiomyopathy. (PMID:19349318)
• Fn14 (TWEAK receptor) is a novel potential mediator of adipogenesis that is expressed differentially in immature-appearing and mature adipocytes and in benign and malignant adipose tissue-derived tumors. (PMID:19828625)
• Tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 interaction may have proinflammatory effects in retinal pigment epithelial cells. TWEAK increased the production of IL-8 and MCP-1 via Fn14. (PMID:19895311)
• These data reveal the TWEAK/Fn14 pathway for regulation of microbial-induced inflammation in the female reproductive tract. (PMID:19963275)
• TWEAK/FN-14 might regulate the effects of interleukin 18 adn 15 in the human endometrium. (PMID:20004376)
• Fn14 expression is high in endometrial cancers and promotes apoptosis of these cancer cells. (PMID:20189297)
• TWEAKR/Fn14 was expressed on the cell membrane and in the cytoplasm of Rheumatoid arthritis fibroblast-like synoviocytes (PMID:20487651)
• The transgenic Fn14/TWEAK receptor pathway in a mouse model is adversely involved in inflammatory and ischemic brain disease associated with the strongest increase of endogenous neuroprotective G-CSF and the G-CSF receptor system. (PMID:20557950)
• Oligomerization of soluble TWEAK differentially affects Fn14-mediated activation of the classical and nonclassical NF-kappa B pathway. (PMID:20610643)
• the TWEAK-Fn14 axis can regulate activation of TF and PAI-1 expression in vascular cells (PMID:20810696)
• Regulation of TWEAKR expression by Kaposi’s sarcoma-associated herpesvirus microRNA prevents TWEAK-induced apoptosis and inflammatory cytokine expression. (PMID:20844036)
• Fn14 expression was highly upregulated in ischemic renal tissues and tubular epithelial cells of biopsies (PMID:20927042)
• REVIEW: TWEAK/Fn14 pathway in tissue remodeling (PMID:21153335)
• Suggest that the renal TWEAK/Fn14 and IP-10/CXCR3 axis may contribute to the pathogenesis of lupus nephritis. (PMID:21303425)
• TWEAK/Fn14 signalling is important in the pathogenesis of inflammation and bone erosion in rheumatoid arthritis. (PMID:21435232)
• This is the first study, presenting together the TNFSF members APRIL, BAFF, TWEAK and their receptors in different areas of normal renal tissue and renal cell carcinoma. (PMID:21483105)
• GRP94, FN14, and inhibin have roles in brain and non-brain metastases in ErbB-2+ and ErbB-2- breast neoplasms (PMID:21708117)
• Overexpression of Fn14 promotes androgen-independent prostate cancer progression through MMP-9. (PMID:21828059)
• effect of Fn14 on cell growth was mediated by the NF-kappaB activity and eventually by the transcriptional regulation of the anti-apoptotic Bcl-2 family gene (PMID:21993017)
• The effect of interaction between TWEAK and its receptor fibroblast growth factor-inducible-14 (Fn14) on cytokine expression in RAFLS. (PMID:22055894)
• binding of TWEAK to Fn14 (PMID:22081603)
• RAR is able to interact with cytoplasmic AFP and binds to the element of the regulatory region of the Fn14 gene in the neoplastic tissue of human hepatocellular carcinoma patients (PMID:22521346)
• Elevated expression of Fn14 in non-small cell lung cancer correlates with activated EGFR and promotes tumor cell migration and invasion. (PMID:22634180)
• Fn14, the receptor for TNF-like weak inducer of apoptosis, is selectively upregulated in patients with Alcoholic Hepatitis. (PMID:22637703)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tnfrsf12a	ENSMUSG00000023905

Protein

Protein identifiers

Tumor necrosis factor receptor superfamily member 12A — Q9NP84 (reviewed: Q9NP84)

Alternative names: Fibroblast growth factor-inducible immediate-early response protein 14, Tweak-receptor

All UniProt accessions (5): Q9NP84, I3L0S4, I3L1J9, I3L3P4, I3L539

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for TNFSF12/TWEAK. Weak inducer of apoptosis in some cell types. Promotes angiogenesis and the proliferation of endothelial cells. May modulate cellular adhesion to matrix proteins.

Subunit / interactions. Associates with TRAF1 and TRAF2, and probably also with TRAF3.

Subcellular location. Membrane.

Tissue specificity. Highly expressed in heart, placenta and kidney. Intermediate expression in lung, skeletal muscle and pancreas.

Induction. By FGF1 and phorbol ester.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NP84-1	1	yes
Q9NP84-2	2

RefSeq proteins (1): NP_057723* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022316	TNFR_12	Family

Pfam: PF12191

UniProt features (16 total): helix 3, disulfide bond 3, strand 2, topological domain 2, signal peptide 1, chain 1, turn 1, transmembrane region 1, repeat 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2EQP	SOLUTION NMR
2KMZ	SOLUTION NMR
2RPJ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NP84-F1	73.82	0.06

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 (3): 36–49, 52–67, 55–64

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5668541	TNFR2 non-canonical NF-kB pathway
R-HSA-5676594	TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway

MSigDB gene sets: 334 (showing top): AP1_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_WOUND_HEALING, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_NEURON_PROJECTION_EXTENSION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_GROWTH, GOCC_CELL_SURFACE, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, MCBRYAN_TERMINAL_END_BUD_UP, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_NEUROGENESIS, RACCACAR_AML_Q6, TGACCTY_ERR1_Q2

GO Biological Process (11): angiogenesis (GO:0001525), substrate-dependent cell migration, cell attachment to substrate (GO:0006931), cell differentiation (GO:0030154), positive regulation of apoptotic process (GO:0043065), regulation of angiogenesis (GO:0045765), positive regulation of axon extension (GO:0045773), regulation of wound healing (GO:0061041), extrinsic apoptotic signaling pathway (GO:0097191), positive regulation of extrinsic apoptotic signaling pathway (GO:2001238), apoptotic process (GO:0006915), cell adhesion (GO:0007155)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): ruffle (GO:0001726), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic signaling pathway	2
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
substrate-dependent cell migration	1
cell-substrate adhesion	1
cellular developmental process	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
angiogenesis	1
regulation of anatomical structure morphogenesis	1
regulation of vasculature development	1
positive regulation of cell growth	1
regulation of axon extension	1
positive regulation of developmental growth	1
axon extension	1
positive regulation of axonogenesis	1
wound healing	1
regulation of response to wounding	1
cell surface receptor signaling pathway	1
extrinsic apoptotic signaling pathway	1
positive regulation of apoptotic signaling pathway	1
regulation of extrinsic apoptotic signaling pathway	1
programmed cell death	1
execution phase of apoptosis	1
cellular process	1
binding	1
cell leading edge	1
plasma membrane bounded cell projection	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1174 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNFRSF12A	TNFSF12	O43508	999
TNFRSF12A	TRAF3	Q13114	869
TNFRSF12A	TRAF5	O00463	861
TNFRSF12A	TNFRSF25	P78507	800
TNFRSF12A	TNFRSF1A	P19438	740
TNFRSF12A	TRAF1	Q13077	718
TNFRSF12A	FGF20	Q9NP95	716
TNFRSF12A	FGF22	Q9HCT0	716
TNFRSF12A	FGF6	P10767	716
TNFRSF12A	FGF16	O43320	716
TNFRSF12A	TRADD	Q15628	715
TNFRSF12A	FGF18	O76093	714
TNFRSF12A	FGF17	O60258	714
TNFRSF12A	FGF5	P12034	713
TNFRSF12A	FGF3	P11487	713

IntAct

33 interactions, top by confidence:

A	B	Type	Score
SLC30A2	TNFRSF12A	psi-mi:“MI:0915”(physical association)	0.780
TNFRSF12A	SLC30A2	psi-mi:“MI:0915”(physical association)	0.780
TNFRSF12A	TNFSF12	psi-mi:“MI:0915”(physical association)	0.760
TNFSF12	TNFRSF12A	psi-mi:“MI:0915”(physical association)	0.760
TNFSF12	TNFRSF12A	psi-mi:“MI:0407”(direct interaction)	0.760
TNFRSF12A	TNFSF12	psi-mi:“MI:0407”(direct interaction)	0.760
KRTAP3-3	TNFRSF12A	psi-mi:“MI:0915”(physical association)	0.560
TNFRSF12A	BIRC2	psi-mi:“MI:0915”(physical association)	0.500
TRAF2	TNFRSF12A	psi-mi:“MI:0915”(physical association)	0.500
TNFRSF12A	TRAF2	psi-mi:“MI:0914”(association)	0.500
TNFRSF12A	TRAF2	psi-mi:“MI:0915”(physical association)	0.500
PSG5	TNFRSF12A	psi-mi:“MI:0915”(physical association)	0.400
KIR2DL5A	TNFRSF12A	psi-mi:“MI:0915”(physical association)	0.400
TNFRSF12A	LILRA1	psi-mi:“MI:0915”(physical association)	0.400
TNFRSF12A	LILRA3	psi-mi:“MI:0915”(physical association)	0.400
TNFRSF12A	LILRA6	psi-mi:“MI:0915”(physical association)	0.400
LILRB3	TNFRSF12A	psi-mi:“MI:0915”(physical association)	0.400
LILRB5	TNFRSF12A	psi-mi:“MI:0915”(physical association)	0.400
TNFRSF12A	TREM2	psi-mi:“MI:0915”(physical association)	0.400
TNFRSF12A	E6	psi-mi:“MI:0915”(physical association)	0.370
MFSD14A	FAM171A2	psi-mi:“MI:0914”(association)	0.350
TNFRSF12A	SLC30A2	psi-mi:“MI:0915”(physical association)	0.000
TNFRSF12A	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): TNFRSF12A (Two-hybrid), TNFRSF12A (Affinity Capture-RNA), TRAF2 (Affinity Capture-Western), SLC30A2 (Two-hybrid), KRTAP3-3 (Two-hybrid), TRAF1 (Reconstituted Complex), TRAF2 (Reconstituted Complex), TNFRSF12A (Affinity Capture-RNA), TNFRSF12A (Negative Genetic), TNFRSF12A (Proximity Label-MS), TNFRSF12A (PCA), TNFRSF12A (Affinity Capture-MS), TNFRSF12A (Affinity Capture-MS), TNFRSF12A (Affinity Capture-RNA), BIRC2 (Affinity Capture-Western)

ESM2 similar proteins: A0A140LIT1, A0A1B0GVG4, A0A494C0Y3, A0JNH6, A0JNN8, A1A5D9, A2ARS0, A5A769, A5PJP1, A6NC98, A7YWC8, C9JTQ0, O15049, O35764, O95502, P0C7N4, P0DPE3, P58660, Q0P5D1, Q1HCM0, Q2TAC2, Q3LUD3, Q3LUD4, Q3TMW1, Q3UMT1, Q4QRL3, Q5BLP8, Q5JTB6, Q6QNY0, Q6QZQ4, Q8BP01, Q8C7U1, Q8CHW5, Q8K262, Q8N283, Q8N6Y0, Q8TAT2, Q8TER5, Q8TF21, Q91XV7

Diamond homologs: Q9CR75, Q9NP84

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
F2RL1	“up-regulates quantity by expression”	TNFRSF12A	“transcriptional regulation”
F2R	“up-regulates quantity by expression”	TNFRSF12A	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	6	43.6×	1e-07
Adaptive Immune System	5	12.4×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
immune response-regulating signaling pathway	6	227.7×	1e-11
adaptive immune response	5	35.1×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

602 predictions. Top by Δscore:

Variant	Effect	Δscore
16:3020488:CCAGG:C	donor_loss	1.0000
16:3020490:AGGT:A	donor_loss	1.0000
16:3020492:G:GC	donor_loss	1.0000
16:3020493:T:G	donor_loss	1.0000
16:3021315:GGGCT:G	donor_gain	1.0000
16:3021316:GGCT:G	donor_gain	1.0000
16:3021316:GGCTG:G	donor_gain	1.0000
16:3021317:GCT:G	donor_gain	1.0000
16:3021317:GCTG:G	donor_gain	1.0000
16:3021320:G:GG	donor_gain	1.0000
16:3020487:GCCAG:G	donor_gain	0.9900
16:3020492:G:GG	donor_gain	0.9900
16:3021288:G:GT	donor_gain	0.9900
16:3021690:G:GG	donor_gain	0.9900
16:3021769:A:AG	acceptor_gain	0.9900
16:3021770:G:GG	acceptor_gain	0.9900
16:3021550:CCCA:C	acceptor_loss	0.9800
16:3021551:CCAG:C	acceptor_loss	0.9800
16:3021770:GC:G	acceptor_gain	0.9800
16:3021770:GCCC:G	acceptor_gain	0.9800
16:3021770:GCCCC:G	acceptor_gain	0.9800
16:3018483:CT:C	acceptor_gain	0.9700
16:3021317:GCTGT:G	donor_loss	0.9700
16:3021318:CT:C	donor_gain	0.9700
16:3021319:TGT:T	donor_loss	0.9700
16:3021320:GT:G	donor_loss	0.9700
16:3021321:TGA:T	donor_loss	0.9700
16:3021553:A:AG	acceptor_gain	0.9700
16:3021554:G:GG	acceptor_gain	0.9700
16:3021687:CCA:C	donor_gain	0.9700

AlphaMissense

802 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:3021308:T:G	F63C	0.998
16:3021307:T:C	F63L	0.997
16:3021309:C:A	F63L	0.997
16:3021309:C:G	F63L	0.997
16:3021684:T:G	F110C	0.997
16:3021683:T:C	F110L	0.995
16:3021685:C:A	F110L	0.995
16:3021685:C:G	F110L	0.995
16:3021614:A:C	S87R	0.993
16:3021616:C:A	S87R	0.993
16:3021616:C:G	S87R	0.993
16:3021684:T:C	F110S	0.993
16:3021246:G:C	W42C	0.992
16:3021246:G:T	W42C	0.992
16:3021247:A:T	S43C	0.990
16:3021308:T:C	F63S	0.988
16:3021777:T:A	I114K	0.987
16:3021248:G:T	S43I	0.986
16:3021265:T:A	C49S	0.986
16:3021266:G:C	C49S	0.986
16:3021284:G:A	C55Y	0.986
16:3021247:A:C	S43R	0.985
16:3021249:C:A	S43R	0.985
16:3021249:C:G	S43R	0.985
16:3021301:A:C	S61R	0.984
16:3021303:C:A	S61R	0.984
16:3021303:C:G	S61R	0.984
16:3021781:G:C	E115D	0.984
16:3021781:G:T	E115D	0.984
16:3021311:G:A	C64Y	0.981

dbSNP variants (sampled 300 via entrez): RS1000273802 (16:3021354 C>T), RS1000512408 (16:3019365 CTTTT>C,CTTT,CTTTTT), RS1000950947 (16:3022677 C>T), RS1001172979 (16:3019173 G>A), RS1001933083 (16:3018881 GGTT>G), RS1002006199 (16:3022250 G>A,C,T), RS1002663492 (16:3019389 G>A,C), RS1003810930 (16:3022219 G>C), RS1003914622 (16:3022459 C>G,T), RS1003951080 (16:3021009 G>T), RS1004892878 (16:3022571 C>T), RS1005175924 (16:3022284 C>T), RS1005340736 (16:3018665 C>G,T), RS1005591189 (16:3019600 A>G), RS1005622187 (16:3019861 C>G,T)

Disease associations

OMIM: gene MIM:605914 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712850 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Tumour necrosis factor (TNF) receptor family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, affects expression, increases abundance, decreases expression	4
Benzo(a)pyrene	increases expression	4
Valproic Acid	affects cotreatment, increases expression	4
bisphenol A	affects expression, affects cotreatment, decreases expression	2
trichostatin A	affects cotreatment, increases expression	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	increases expression	2
Dexamethasone	decreases expression, affects cotreatment	2
Estradiol	decreases reaction, increases expression, decreases expression	2
Hydrogen Peroxide	affects expression, increases expression	2
Nickel	increases expression	2
Ozone	affects expression, increases abundance, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tunicamycin	increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	increases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
beta-lapachone	increases expression	1
arsenite	increases expression, affects reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
ochratoxin A	decreases expression, affects cotreatment	1
potassium chromate(VI)	decreases expression, affects cotreatment	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TT07	HAP1 TNFRSF12A (-) 1	Cancer cell line	Male
CVCL_XU55	HAP1 TNFRSF12A (-) 2	Cancer cell line	Male
CVCL_XU56	HAP1 TNFRSF12A (-) 3	Cancer cell line	Male
CVCL_XU57	HAP1 TNFRSF12A (-) 4	Cancer cell line	Male
CVCL_XU58	HAP1 TNFRSF12A (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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