TNFAIP8

Summary

TNFAIP8 (TNF alpha induced protein 8, HGNC:17260) is a protein-coding gene on chromosome 5q23.1, encoding Tumor necrosis factor alpha-induced protein 8 (O95379). Acts as a negative mediator of apoptosis and may play a role in tumor progression.

Enables cysteine-type endopeptidase inhibitor activity involved in apoptotic process. Involved in positive regulation of apoptotic process. Located in cytoplasm and nucleoplasm.

Source: NCBI Gene 25816 — RefSeq curated summary.

At a glance

• GWAS associations: 68
• Clinical variants (ClinVar): 27 total — 1 pathogenic
• MANE Select transcript: NM_014350

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17260
Approved symbol	TNFAIP8
Name	TNF alpha induced protein 8
Location	5q23.1
Locus type	gene with protein product
Status	Approved
Aliases	GG2-1, MDC-3.13, SCC-S2
Ensembl gene	ENSG00000145779
Ensembl biotype	protein_coding
OMIM	612111
Entrez	25816

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000274456, ENST00000388882, ENST00000415806, ENST00000503646, ENST00000504642, ENST00000504771, ENST00000513374

RefSeq mRNA: 6 — MANE Select: NM_014350 NM_001077654, NM_001286813, NM_001286814, NM_001286815, NM_001286817, NM_014350

CCDS: CCDS47257, CCDS47258, CCDS68933

Canonical transcript exons

ENST00000504771 — 2 exons

Exon	Start	End
ENSE00002058606	119356019	119356121
ENSE00003695402	119392816	119399688

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 97.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 52.2875 / max 2154.2775, expressed in 1812 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58111	23.6427	1783
58133	15.6918	820
58132	3.1008	451
58110	2.1360	1109
58129	2.0119	731
58118	2.0051	156
58131	0.6922	264
58117	0.5024	106
58130	0.4655	200
203669	0.4187	196

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	97.90	gold quality
epithelium of nasopharynx	UBERON:0001951	97.59	gold quality
nasopharynx	UBERON:0001728	97.57	gold quality
vermiform appendix	UBERON:0001154	96.41	gold quality
bone marrow	UBERON:0002371	96.13	gold quality
leukocyte	CL:0000738	96.10	gold quality
mononuclear cell	CL:0000842	96.03	gold quality
monocyte	CL:0000576	96.01	gold quality
lymph node	UBERON:0000029	95.85	gold quality
bone marrow cell	CL:0002092	95.81	gold quality
trabecular bone tissue	UBERON:0002483	95.61	gold quality
esophagus squamous epithelium	UBERON:0006920	95.36	gold quality
palpebral conjunctiva	UBERON:0001812	95.30	gold quality
bone element	UBERON:0001474	94.90	gold quality
choroid plexus epithelium	UBERON:0003911	94.54	gold quality
secondary oocyte	CL:0000655	94.42	gold quality
granulocyte	CL:0000094	94.39	gold quality
parietal pleura	UBERON:0002400	93.86	gold quality
skin of hip	UBERON:0001554	93.68	gold quality
upper leg skin	UBERON:0004262	93.68	gold quality
blood	UBERON:0000178	93.65	gold quality
caecum	UBERON:0001153	93.63	gold quality
placenta	UBERON:0001987	93.48	gold quality
spleen	UBERON:0002106	93.43	gold quality
epithelium of esophagus	UBERON:0001976	93.06	gold quality
germinal epithelium of ovary	UBERON:0001304	92.97	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.88	gold quality
bronchial epithelial cell	CL:0002328	92.34	gold quality
oral cavity	UBERON:0000167	92.24	gold quality
pleura	UBERON:0000977	92.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO3, NR2F1, NR2F2, TLX3

miRNA regulators (miRDB)

70 targeting TNFAIP8, 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-9-5P	100.00	72.28	2361
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-3942-3P	99.57	69.03	2854

Literature-anchored findings (GeneRIF, showing 40)

• SCC-S2 is a novel oncogenic factor in cancer cells (PMID:14724590)
• A chicken ovalbumin upstream promoter transcription factor I (COUP-TFI) complex represses expression of the gene encoding tumor necrosis factor alpha-induced protein 8 (TNFAIP8). (PMID:19112178)
• SCC-S2 plays an important role in NSCLC and might be a useful therapeutic target of NSCLC. (PMID:20398053)
• Findings demonstrate that TNFAIP8 is one of critical components of a signal transduction pathway that links mesangial cell proliferation to diabetic renal injury. (PMID:20699119)
• results showed stronger staining of TNFAIP8 protein in pancreatic cancer tissues compared with normal pancreas tissue; TNFAIP8 expression positively correlated with EGFR levels; results indicate TNFAIP8 may play important roles in the progression of pancreatic cancer (PMID:22631659)
• polymorphism of TNFAIP8 rs1045241C>T may contribute to NHL susceptibility in a Chinese population (PMID:22666399)
• SCC-S2 is overexpressed in colon cancers. (PMID:22886548)
• TNFAIP8 functions in oncogenesis are likely to involve activation of the integrin, MMP and VEGFR-2 signaling pathways. TNFAIP8 expression revealed correlation of both cytoplasmic and nuclear TNFAIP8 overexpression with high grade prostatic adenocarcinomas (PMID:23280553)
• the TNFAIP8-rs11064 Single nucleotide polymorphism may function by affecting the affinity of miR-22 binding to the 3’-untranslated region of TNFAIP8 and regulating TNFAIP8 expression, thus contributing to cervical cancer risk (PMID:23299407)
• These results provide evidence that TNFAIP8 plays critical roles in non-small cell lung cancer (PMID:24136748)
• SCC-S2 may play roles in affecting both immune cells and tumor cells in the thyroid and may indicate a novel pathway for understanding the pathogenesis of the disease. (PMID:24464924)
• TNFAIP8 may be used as a prognostic marker for the recurrence of endometrial cancer (EC), and its promotion of the proliferation and metastasis in EC may be due to its mediation of Ki-67 and MMP9. (PMID:24590269)
• Our data suggest that TNFAIP8 overexpression may contribute to lymph node metastasis and poor prognosis in intestinal-type gastric adenocarcinoma. (PMID:24621012)
• our findings indicate that TNFAIP8 overexpression is an independent predictor of platinum resistance in epithelial ovarian cancer (PMID:24767861)
• Expression of TNFAIP8 is up-regulated in human gastric cancer and regulates cell proliferation, invasion and migration. (PMID:25936980)
• expression associated with cell survival and death in cancer cell lines infected with canine distemper virus (PMID:26373887)
• these findings suggest that TNFAIP8 overexpression is a potential biomarker to identify pN0 esophageal squamous cell carcinoma patients at higher risk of lymphatic recurrence who may benefit from adjuvant therapy. (PMID:26886285)
• Of these, three CpG sites on TNFAIP8 and PON1 genes (corresponding to: cg23917399; cg07086380; and cg07404485, respectively) were significantly differentially methylated between black and non-black individuals. The three CpG sites showed lower methylation status among infants of black women. (PMID:27000849)
• induction of TNFAIP8 is critical for the evasion of apoptosis by tumor cells expressing the K120R variant of p53. (PMID:27341992)
• TNFAIP8 seems to regulate the cell survival and cancer progression processes in a multifaceted manner. (Review) (PMID:27807832)
• TNFAIP8 v2 may contribute to both carcinogenesis and chemotherapeutic resistance by broadly suppressing p53 activity, thus offsetting p53-dependent tumor suppression. (PMID:27834950)
• TNFAIP8 overexpression is correlated with axillary lymph node metastasis and poor prognosis in invasive ductal breast carcinoma. (PMID:28087477)
• that MicroRNA-9-TNFAIP8 might represent a promising diagnostic biomarker for gastric cancer patients and could be a potential therapeutic target in the prevention and treatment of gastric cancer (PMID:28127811)
• TNFAIP8 regulates Hippo (MST1/2) signaling through its interaction with LATS1. (PMID:28152516)
• TNFAIP8 regulates Hippo pathway through interacting with LATS1 to promote cell proliferation. (PMID:28926138)
• The indel chr5:118704153:D, located within TNFAIP8, showed an association with plantar fascial disorders at genome-wide significance (p<5x10(-8)) with small effects (odds ratios=0.93 and 1.07 per allele, respectively). (PMID:29534260)
• role of TNFAIP8 in NSCLC proliferation and cisplatin chemoresistance that is mediated through the MDM2/p53 pathway (PMID:30064446)
• SCC-S2 Facilitates Tumor Proliferation and Invasion via Activating Wnt Signaling and Depressing Hippo Signaling in Colorectal Cancer Cells and Predicts Poor Prognosis of Patients (PMID:30216108)
• this review focused on the expression, regulation, structural aspects, modifications/interactions, and oncogenic role of TNFAIP8 proteins in human cancers. [Review] (PMID:30586922)
• TNFAIP8 regulates autophagy, cell steatosis, and promotes hepatocellular carcinoma cell proliferation. (PMID:32152268)
• TNFAIP8 regulates cisplatin resistance through TAF-Ialpha and promotes malignant progression of esophageal cancer. (PMID:32432789)
• TNFAIP8 promotes AML chemoresistance by activating ERK signaling pathway through interaction with Rac1. (PMID:32795319)
• Inflection of Akt/mTOR/STAT-3 cascade in TNF-alpha induced protein 8 mediated human lung carcinogenesis. (PMID:32976884)
• TNFAIP8 drives metabolic reprogramming to promote prostate cancer cell proliferation. (PMID:33227392)
• Proteomic Analysis of Plasma sEVs Reveals That TNFAIP8 Is a New Biomarker of Cell Proliferation in Diabetic Retinopathy. (PMID:33594895)
• TNFAIP8 regulates gastric cancer growth via mTOR-Akt-ULK1 pathway and autophagy signals. (PMID:33682317)
• Current research status of TNFAIP8 in tumours and other inflammatory conditions (Review). (PMID:34036374)
• Decoupling tumor cell metastasis from growth by cellular pilot protein TNFAIP8. (PMID:34608264)
• Kidney tubular epithelial cells control interstitial fibroblast fate by releasing TNFAIP8-encapsulated exosomes. (PMID:37828075)
• Synovial fluid exosome-derived miR-182-5p alleviates osteoarthritis by downregulating TNFAIP8 and promoting autophagy through LC3 signaling. (PMID:37948986)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tnfaip8	ENSMUSG00000062210
rattus_norvegicus	Tnfaip8	ENSRNOG00000026136
drosophila_melanogaster	sigmar	FBGN0034894

Paralogs (3): TNFAIP8L2 (ENSG00000163154), TNFAIP8L3 (ENSG00000183578), TNFAIP8L1 (ENSG00000185361)

Protein

Protein identifiers

Tumor necrosis factor alpha-induced protein 8 — O95379 (reviewed: O95379)

Alternative names: Head and neck tumor and metastasis-related protein, MDC-3.13, NF-kappa-B-inducible DED-containing protein, SCC-S2, TNF-induced protein GG2-1

All UniProt accessions (4): D6RCM8, E5RIJ3, J3KQT8, O95379

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a negative mediator of apoptosis and may play a role in tumor progression. Suppresses the TNF-mediated apoptosis by inhibiting caspase-8 activity but not the processing of procaspase-8, subsequently resulting in inhibition of BID cleavage and caspase-3 activation.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed at high levels in the spleen, lymph node, thymus, thyroid, bone marrow and placenta. Expressed at high levels both in various tumor tissues, unstimulated and cytokine-activated cultured cells. Expressed at low levels in the spinal cord, ovary, lung, adrenal glands, heart, brain, testis and skeletal muscle.

Induction. By nuclear factor-KB (NF-KB) and TNF. Induction by TNF depends upon activation of NF-KB.

Similarity. Belongs to the TNFAIP8 family.

Isoforms (4)

UniProt ID	Names	Canonical?
O95379-1	1	yes
O95379-2	2
O95379-3	3
O95379-4	4

RefSeq proteins (6): NP_001071122, NP_001273742, NP_001273743, NP_001273744, NP_001273746, NP_055165* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008477	TNFAIP8-like	Family
IPR038355	TNFAIP8_sf	Homologous_superfamily

Pfam: PF05527

UniProt features (6 total): splice variant 3, chain 1, coiled-coil region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95379-F1	89.83	0.74

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1483255	PI Metabolism
R-HSA-1430728	Metabolism
R-HSA-1483257	Phospholipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 317 (showing top): MCLACHLAN_DENTAL_CARIES_UP, BASSO_HAIRY_CELL_LEUKEMIA_DN, MODULE_45, HALMOS_CEBPA_TARGETS_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GENTILE_RESPONSE_CLUSTER_D3, MODULE_16, AAAYRNCTG_UNKNOWN, HINATA_NFKB_TARGETS_KERATINOCYTE_UP, RICKMAN_METASTASIS_DN, ONKEN_UVEAL_MELANOMA_UP, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, LE_EGR2_TARGETS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (4): apoptotic process (GO:0006915), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), regulation of apoptotic process (GO:0042981)

GO Molecular Function (2): cysteine-type endopeptidase inhibitor activity involved in apoptotic process (GO:0043027), protein binding (GO:0005515)

GO Cellular Component (2): nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Phospholipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	3
regulation of apoptotic process	2
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
regulation of programmed cell death	1
cysteine-type endopeptidase regulator activity involved in apoptotic process	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNFAIP8	CFLAR	O15519	625
TNFAIP8	MMP1	P03956	563
TNFAIP8	TNF	P01375	535
TNFAIP8	KDR	P35968	470
TNFAIP8	MMP9	P14780	441
TNFAIP8	TTLL1	O95922	419
TNFAIP8	RIC8A	Q9NPQ8	417
TNFAIP8	RASA3	Q14644	416
TNFAIP8	TNFAIP2	Q03169	410
TNFAIP8	TNFAIP3	P21580	409
TNFAIP8	H1-2	P16403	373
TNFAIP8	CLECL1	Q8IZS7	318
TNFAIP8	FBXW5	Q969U6	317
TNFAIP8	TNFAIP6	P98066	305
TNFAIP8	CASP8	Q14790	305

IntAct

53 interactions, top by confidence:

A	B	Type	Score
TNFAIP8	MED4	psi-mi:“MI:0915”(physical association)	0.780
MED4	TNFAIP8	psi-mi:“MI:0915”(physical association)	0.780
SDCBP	TNFAIP8	psi-mi:“MI:0915”(physical association)	0.720
TNFAIP8	PRR13	psi-mi:“MI:0915”(physical association)	0.720
TNFAIP8	SDCBP	psi-mi:“MI:0915”(physical association)	0.720
PRR13	TNFAIP8	psi-mi:“MI:0915”(physical association)	0.720
PLEKHF2	TNFAIP8	psi-mi:“MI:0915”(physical association)	0.670
INO80E	TNFAIP8	psi-mi:“MI:0915”(physical association)	0.560
TIFA	TNFAIP8	psi-mi:“MI:0915”(physical association)	0.560
TNFAIP8	INO80E	psi-mi:“MI:0915”(physical association)	0.560
TNFAIP8	TIFA	psi-mi:“MI:0915”(physical association)	0.560
TNFAIP8	ATN1	psi-mi:“MI:0915”(physical association)	0.560
TNFAIP8	PLEKHF1	psi-mi:“MI:0915”(physical association)	0.560
TNFAIP8	EAF1	psi-mi:“MI:0915”(physical association)	0.560
TNFAIP8	EAPP	psi-mi:“MI:0915”(physical association)	0.560
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480

BioGRID (48): TNFAIP8 (Two-hybrid), MED4 (Two-hybrid), PRR13 (Two-hybrid), PLEKHF2 (Two-hybrid), TIFA (Two-hybrid), INO80E (Two-hybrid), TNFAIP8 (Affinity Capture-RNA), MED4 (Two-hybrid), PLEKHF2 (Two-hybrid), LATS1 (Affinity Capture-Western), TNFAIP8 (Affinity Capture-Western), TNFAIP8 (Affinity Capture-RNA), PTP4A2 (Affinity Capture-MS), PTP4A1 (Affinity Capture-MS), TNFAIP8 (Affinity Capture-MS)

ESM2 similar proteins: A0KHF9, A4IF78, A4SQI6, B5X737, C5E1D0, O34950, O60083, O95379, P01579, P02243, P0CA45, P20147, P28341, P33754, P38581, P38582, P42162, P63309, P63310, P63311, P68581, P68582, Q10012, Q10420, Q1ECV8, Q28I19, Q28ZG0, Q3IH15, Q3TBL6, Q4R8E8, Q4V8P4, Q5BKH4, Q5I6S9, Q5RF18, Q5ZI78, Q5ZJU8, Q6DF07, Q6DFE2, Q6GQ44, Q6NWL1

Diamond homologs: A4IF78, A5PK29, A9X192, B0KWC3, B2KI57, B4UT01, B5X737, B7NZC7, O95379, Q1ECV8, Q28I19, Q28ZG0, Q3TBL6, Q3ZBK5, Q5BKH4, Q5GJ75, Q5RF18, Q5ZI78, Q5ZJU8, Q6AYJ8, Q6DFE2, Q6GQ44, Q6P589, Q6P7I6, Q7KVH9, Q7SZE8, Q7T364, Q7T3D0, Q8K288, Q8WVP5, Q921Z5, Q9D8Y7

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
GNAI3	“up-regulates activity”	TNFAIP8	binding
GNAI1	“up-regulates activity”	TNFAIP8	binding
GNAI2	“up-regulates activity”	TNFAIP8	binding
miR-455-5p	“down-regulates quantity by destabilization”	TNFAIP8	“post transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
685538	GRCh37/hg19 5q21.3-23.1(chr5:108304806-121335239)x1	Pathogenic

SpliceAI

1062 predictions. Top by Δscore:

Variant	Effect	Δscore
5:119268906:GA:G	donor_gain	1.0000
5:119268908:G:GG	donor_gain	1.0000
5:119392814:A:AG	acceptor_gain	1.0000
5:119392814:AGT:A	acceptor_gain	1.0000
5:119392814:AGTG:A	acceptor_gain	1.0000
5:119392815:G:GA	acceptor_gain	1.0000
5:119392815:GT:G	acceptor_gain	1.0000
5:119392815:GTG:G	acceptor_gain	1.0000
5:119392815:GTGG:G	acceptor_gain	1.0000
5:119392815:GTGGC:G	acceptor_gain	1.0000
5:119268907:AGTA:A	donor_loss	0.9900
5:119268908:GTAAG:G	donor_loss	0.9900
5:119268909:TAAGT:T	donor_loss	0.9900
5:119268910:AAGTG:A	donor_loss	0.9900
5:119308308:C:T	donor_gain	0.9900
5:119268903:TCCGA:T	donor_gain	0.9800
5:119268904:CCGA:C	donor_gain	0.9800
5:119268905:CGA:C	donor_gain	0.9800
5:119268906:GAG:G	donor_gain	0.9800
5:119356119:A:T	donor_gain	0.9800
5:119392816:T:TA	acceptor_gain	0.9800
5:119356118:G:GT	donor_gain	0.9700
5:119269027:G:GG	donor_gain	0.9600
5:119269021:GT:G	donor_gain	0.9500
5:119392810:TTTTA:T	acceptor_gain	0.9500
5:119392811:TTTA:T	acceptor_gain	0.9500
5:119392812:TTAGT:T	acceptor_gain	0.9500
5:119392813:TAG:T	acceptor_gain	0.9500
5:119392814:A:T	acceptor_gain	0.9500
5:119392815:G:C	acceptor_gain	0.9500

AlphaMissense

1337 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:119393130:T:C	F116L	0.999
5:119393132:C:A	F116L	0.999
5:119393132:C:G	F116L	0.999
5:119393013:A:G	K77E	0.998
5:119393015:G:C	K77N	0.998
5:119393015:G:T	K77N	0.998
5:119393025:A:G	K81E	0.998
5:119393127:A:C	S115R	0.998
5:119393129:T:A	S115R	0.998
5:119393129:T:G	S115R	0.998
5:119393151:T:C	F123L	0.998
5:119393153:T:A	F123L	0.998
5:119393153:T:G	F123L	0.998
5:119393224:T:C	L147P	0.998
5:119392900:C:A	A39D	0.997
5:119392945:T:C	L54P	0.997
5:119393008:T:C	L75P	0.997
5:119393027:G:C	K81N	0.997
5:119393027:G:T	K81N	0.997
5:119392849:C:A	A22D	0.996
5:119393113:C:A	A110D	0.996
5:119393245:G:C	R154P	0.996
5:119392923:A:C	S47R	0.995
5:119392925:T:A	S47R	0.995
5:119392925:T:G	S47R	0.995
5:119393056:T:C	F91S	0.995
5:119393248:T:A	V155D	0.995
5:119393038:T:C	L85P	0.994
5:119393110:T:C	L109P	0.994
5:119393112:G:C	A110P	0.994

dbSNP variants (sampled 300 via entrez): RS1000021812 (5:119300246 A>G), RS1000028936 (5:119370072 G>C), RS1000042573 (5:119291521 A>G), RS1000051197 (5:119301559 A>G), RS1000061478 (5:119369860 A>G), RS1000079582 (5:119330248 C>A,T), RS1000144416 (5:119378073 A>G,T), RS1000241987 (5:119295639 T>G), RS1000253649 (5:119270871 A>G), RS1000275441 (5:119344893 G>A), RS1000281886 (5:119380057 C>CTAT), RS1000284705 (5:119271186 T>A), RS1000292481 (5:119375193 A>G), RS1000302057 (5:119304569 G>A,T), RS1000339023 (5:119311384 A>C,G)

Disease associations

OMIM: gene MIM:612111 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

68 associations (top):

Study	Trait	p-value
GCST002379_3	Pyoderma gangrenosum in inflammatory bowel disease	7.000000e-06
GCST002579_12	Heschl’s gyrus morphology	6.000000e-06
GCST002782_39	Waist-to-hip ratio adjusted for body mass index	7.000000e-12
GCST002782_40	Waist-to-hip ratio adjusted for body mass index	4.000000e-07
GCST002782_41	Waist-to-hip ratio adjusted for body mass index	4.000000e-12
GCST002782_42	Waist-to-hip ratio adjusted for body mass index	2.000000e-07
GCST004064_55	Waist-hip ratio	3.000000e-08
GCST004505_1	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	3.000000e-09
GCST005038_20	Allergic disease (asthma, hay fever or eczema)	4.000000e-09
GCST005558_1	Plantar fascial disorders	3.000000e-08
GCST005956_40	Waist-to-hip ratio adjusted for BMI	2.000000e-06
GCST005958_18	Waist-to-hip ratio adjusted for BMI (age >50)	9.000000e-07
GCST005959_23	Waist-to-hip ratio adjusted for BMI x sex interaction	3.000000e-06
GCST005962_27	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	9.000000e-09
GCST006611_93	HDL cholesterol	9.000000e-09
GCST006613_84	Triglycerides	6.000000e-11
GCST008159_36	Waist-to-hip ratio adjusted for BMI	8.000000e-06
GCST008916_66	Asthma	6.000000e-10
GCST009597_72	Multiple sclerosis	3.000000e-08
GCST009720_35	Asthma	2.000000e-09
GCST009798_70	Asthma	3.000000e-11
GCST010042_136	Asthma	4.000000e-11
GCST010043_127	Asthma	4.000000e-12
GCST010173_79	Triglyceride levels	4.000000e-13
GCST010241_322	Apolipoprotein A1 levels	2.000000e-08
GCST010242_307	HDL cholesterol levels	2.000000e-14
GCST010244_261	Triglyceride levels	2.000000e-20
GCST011743_86	HDL cholesterol levels in HIV infection	1.000000e-05
GCST90002388_319	Lymphocyte count	2.000000e-30
GCST90002389_210	Lymphocyte percentage of white cells	2.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0006835	pyoderma gangrenosum
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004343	waist-hip ratio
EFO:0004318	smoking behavior
EFO:1001909	Plantar Fasciitis
EFO:0008343	sex interaction measurement
EFO:0008007	age at assessment
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	4
Valproic Acid	decreases expression, affects cotreatment, increases expression, affects expression	4
bisphenol A	affects cotreatment, increases methylation, decreases methylation, increases expression	3
Cadmium	affects expression, increases abundance, decreases expression, increases expression	3
Cisplatin	increases expression, decreases response to substance	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
Cyclosporine	increases expression, decreases expression	3
bisphenol F	increases expression, affects cotreatment	2
nickel chloride	increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Zoledronic Acid	increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Vehicle Emissions	decreases methylation, increases abundance, increases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Estradiol	affects cotreatment, decreases expression	2
Smoke	decreases expression, increases abundance	2
Aflatoxin B1	decreases methylation, increases expression, affects expression	2
Asbestos, Serpentine	affects expression, decreases methylation	2
Asbestos, Crocidolite	affects expression, increases expression	2
Cadmium Chloride	decreases expression, affects expression, increases abundance	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
trichostatin A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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