TIPE2

Summary

TIPE2 (TNF alpha induced protein 8 like 2, HGNC:26277) is a protein-coding gene on chromosome 1q21.3, encoding Tumor necrosis factor alpha-induced protein 8-like protein 2 (Q6P589). Acts as a negative regulator of innate and adaptive immunity by maintaining immune homeostasis.

Predicted to be involved in negative regulation of T cell activation and negative regulation of inflammatory response. Predicted to be located in lysosome and nucleus. Predicted to be active in cytoplasm.

Source: NCBI Gene 79626 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• MANE Select transcript: NM_024575

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26277
Approved symbol	TIPE2
Name	TNF alpha induced protein 8 like 2
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23467
Ensembl gene	ENSG00000163154
Ensembl biotype	protein_coding
OMIM	612112
Entrez	79626

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000368910, ENST00000901231, ENST00000901232

RefSeq mRNA: 1 — MANE Select: NM_024575 NM_024575

CCDS: CCDS985

Canonical transcript exons

ENST00000368910 — 2 exons

Exon	Start	End
ENSE00001448273	151158666	151159749
ENSE00001448274	151156649	151156722

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 96.29.

FANTOM5 (CAGE): breadth broad, TPM avg 6.4604 / max 136.8796, expressed in 514 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5207	6.4604	514
5206	2.8648	422

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.29	gold quality
leukocyte	CL:0000738	94.90	gold quality
monocyte	CL:0000576	94.71	gold quality
blood	UBERON:0000178	93.35	gold quality
ileal mucosa	UBERON:0000331	90.18	gold quality
spleen	UBERON:0002106	90.06	gold quality
vermiform appendix	UBERON:0001154	87.47	gold quality
lymph node	UBERON:0000029	84.63	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.03	gold quality
trabecular bone tissue	UBERON:0002483	81.28	gold quality
bone marrow	UBERON:0002371	80.04	gold quality
superficial temporal artery	UBERON:0001614	78.03	gold quality
caecum	UBERON:0001153	77.40	gold quality
right coronary artery	UBERON:0001625	77.21	gold quality
gall bladder	UBERON:0002110	75.74	gold quality
rectum	UBERON:0001052	75.17	gold quality
right lung	UBERON:0002167	74.79	gold quality
right adrenal gland cortex	UBERON:0035827	73.79	gold quality
upper lobe of left lung	UBERON:0008952	73.78	gold quality
smooth muscle tissue	UBERON:0001135	73.47	gold quality
upper lobe of lung	UBERON:0008948	73.46	gold quality
mucosa of transverse colon	UBERON:0004991	73.40	gold quality
bone marrow cell	CL:0002092	73.38	gold quality
small intestine Peyer’s patch	UBERON:0003454	73.35	gold quality
apex of heart	UBERON:0002098	73.13	gold quality
right adrenal gland	UBERON:0001233	72.93	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	72.90	gold quality
left coronary artery	UBERON:0001626	72.46	gold quality
cardiac muscle of right atrium	UBERON:0003379	71.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting TIPE2, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-6878-5P	98.49	67.91	2142

Literature-anchored findings (GeneRIF, showing 40)

• High levels of TIPE2 were detected in monocyte/macrophage derived cell lines and ovarian adenocarcinoma cells, but not detectable or weakly expressed in most human carcinoma cell lines. (PMID:20663561)
• The unique expressional profile of human TIPE2 suggests new functions beyond controlling innate and adaptive immunity. (PMID:21459448)
• These results indicate that TIPE2 plays an important role in taming Hepatitis B virus-induced hepatic inflammation. (PMID:21466895)
• TIPE2 is an inhibitor of both inflammation and cancer, and a potential drug target for inflammatory and neoplastic diseases. (PMID:22326055)
• Letter: detection of TIPE2 in the blood samples may be used as one of the diagnosis molecular markers in clinical monitoring kidney chronic rejection. (PMID:23009108)
• TIPE2 mRNA and protein expression were decreased in children with asthma compared with healthy controls. (PMID:24107080)
• Human TIPE2 is an endogenous inhibitor of Rac1 in hepatocellular carcinoma (HCC) by which it attenuates invasion and metastasis of HCC. (PMID:24274578)
• These results strongly suggest that TIPE2 plays an important role in shifting L-arginase metabolism from production of NO to urea, during host inflammatory response. (PMID:24806446)
• TIPE2 can inhibit caspase-8 activity in colon cancer cells. TIPE2 can regulate TLR4 inflammatory effect and inhibit further amplification of cascade reaction via caspase-8. (PMID:24934366)
• Both TNF-alpha and TIPE2 might be potential targets for the treatment of hepatocellular carcinoma metastasis. (PMID:25339267)
• TIPE2 plays an important role in regulating hepatitis B virus-specific CD8(+) T cell functions in patients with hepatitis B. (PMID:25499447)
• Tumor necrosis factor-alpha-induced protein-8 like-2 (TIPE2) upregulates p27 to decrease gastic cancer cell proliferation (PMID:25536447)
• TIPE2 might serve as a tumor suppressor in non-small cell lung cancer progression. (PMID:25542151)
• TIPE2 promoted lung cancer cell apoptosis through affecting apoptosis-related molecules caspase-3, caspase-9, Bcl-2 and Bax, possibly via regulating P38 and Akt pathways. (PMID:25946186)
• TIPE2 mRNA showed sensitivity of 74.63%, specificity of 90.24%, positive predictive value of 92.5%, and negative predictive value of 67.3% for predicting 3-month mortality in Acute-on-Chronic Hepatitis B Liver Failure. (PMID:26426653)
• The TIPE2-elicited antimetastatic effect in gastric cancer was closely associated with the inhibition of AKT signaling and enhancement of GSK3b activity followed by the degradation and decreased translocation to nucleus of b-catenin (PMID:26530498)
• our data suggest a previously unappreciated role of TIPE2 in the crosstalk between skin SCC and TAMs and highlight TIPE2 as a promising novel target for skin SCC treatment. (PMID:26577853)
• Insufficient expression of TIPE2 might be involved in the hyperreactivity of monocyte to Toll-like receptor ligands in primary biliary cirrhosis. (PMID:26644386)
• Results provide evidence that TIPE2 acts as an inhibitor of gastric cancer cell growth and triggers an IRF4-associated signaling cascade that promotes p27 expression and restores control of cell proliferation. (PMID:26781452)
• TIPE2 suppressed tumor invasiveness and angiogenesis in non-small cell lung cancer via inhibiting the activation of Rac1 and subsequently weakening its downstream effects, including F-actin polymerization and VEGF expression. (PMID:27556698)
• the expression of TIPE2 protein could be a predictor of better prognosis for DLBCL. (PMID:27578327)
• these data suggest that TIPE2 overexpression inhibited hypoxia-induced Wnt/beta-catenin pathway activation and EMT in glioma cells. (PMID:27656836)
• Low expression of TIPE2 is associated with hepatocellular carcinogenesis. (PMID:27696294)
• Authors demonstrated that TIPE2 overexpression may suppress proliferation, migration, and invasion in prostate cancer cells by inhibiting the PI3K/Akt signaling pathway. (PMID:27712587)
• TIPE2 suppressed breast cancer tumorigenesis, growth and metastasis possibly via regulation of the AKT and p38 signaling pathways. (PMID:27779698)
• Further MD simulations confirmed the dynamic stability of these lipids in the TH domain. This computational analysis thus provides insight into the binding mode of phospholipids in the TH domain of the TIPE family of proteins. (PMID:27783229)
• this study shows that TIPE2 contributes to the pathogenesis of ankylosing spondylitis (PMID:27816498)
• TIPE2 expression was significantly decreased in human breast cancer tissue and cell lines. Overexpression of TIPE2 inhibited the proliferation in vitro and tumor xenograft growth in vivo. TIPE2 also inhibited the migration/invasion of breast cancer cells through preventing the epithelial-to-mesenchymal transition (EMT) phenotype. (PMID:28081733)
• data provided the first evidence that TIPE2 inhibits gastric cancer cell migration, invasion and metastasis very probably via reversal of EMT, revealing that TIPE2 may be a novel therapeutic target for human gastric cancer EMT and metastasis. (PMID:28186089)
• TIPE2 inhibited the expression of asthma-related inflammatory factors in hyperstretched BEAS-2B cells by suppressing the Wnt/beta-catenin signaling pathway. (PMID:28188409)
• TIPE2 might be associated with immune clearance of patients with chronic hepatitis B. (PMID:28390195)
• TIPE2 may participate in T2DM by regulating TNF-alpha production (PMID:28626770)
• In conclusion, for the first time, we discovered that the Th2 milieu is able to upregulate TIPE2 expression in macrophages, which facilitates the change in macrophage phenotype and function and, in turn, potentially exaggerates eosinophilic inflammation and disease progression in chronic rhinosinusitis with nasal polyps. (PMID:28665518)
• The expression of TIPE2 in THP1 cells may be upregulated by Poly I:C. (PMID:28849057)
• TIPE2 could play important roles in maintaining the maternal-fetal tolerance and decreased TIPE2 expression in the decidua may be related to the development of missed abortion. (PMID:28851386)
• our data indicated that TIPE2 expressed in macrophages might play a negative role in MP triggered immune response via inhibiting MAPK signaling pathway. (PMID:29042627)
• Our study identifies the molecular mechanisms underlying the interplay of TNF-alpha, TIPE2, and apoptosis during allograft rejection, and it suggests that both TNF-alpha and TIPE2 might be potential targets for the successfully grafted corneal endothelium. (PMID:29480366)
• Low TIPE2 expression is associated with Gastric cancer. (PMID:30015980)
• Increased serum levels of TIPE2 are positively related to age and severity of Parkinson’s disease. (PMID:30105613)
• TIPE2 sensitizes osteosarcoma cells to cis-platin through downregulation of MDR1 and may be a novel target in osteosarcoma therapy. (PMID:30114619)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tnfaip8l2b	ENSDARG00000046148
danio_rerio	tnfaip8l2a	ENSDARG00000075592
mus_musculus	Tnfaip8l2	ENSMUSG00000013707
rattus_norvegicus	Tnfaip8l2	ENSRNOG00000021100
drosophila_melanogaster	sigmar	FBGN0034894

Paralogs (3): TNFAIP8 (ENSG00000145779), TNFAIP8L3 (ENSG00000183578), TNFAIP8L1 (ENSG00000185361)

Protein

Protein identifiers

Tumor necrosis factor alpha-induced protein 8-like protein 2 — Q6P589 (reviewed: Q6P589)

Alternative names: Inflammation factor protein 20

All UniProt accessions (1): Q6P589

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a negative regulator of innate and adaptive immunity by maintaining immune homeostasis. Plays a regulatory role in the Toll-like signaling pathway by determining the strength of LPS-induced signaling and gene expression. Inhibits TCR-mediated T-cell activation and negatively regulate T-cell function to prevent hyperresponsiveness. Also inhibits autolysosome formation via negatively modulating MTOR activation by interacting with RAC1 and promoting the disassociation of the RAC1-MTOR complex. Plays an essential role in NK-cell biology by acting as a checkpoint and displaying an expression pattern correlating with NK-cell maturation process and by negatively regulating NK-cell maturation and antitumor immunity. Mechanistically, suppresses IL-15-triggered mTOR activity in NK-cells.

Subunit / interactions. May interact with CASP8; however, such result is unclear since PubMed:19079267 could not reproduce the interaction with CASP8. Interacts with RAC1.

Subcellular location. Cytoplasm. Nucleus. Lysosome.

Tissue specificity. Expressed in T-cells, B-cells, macrophages, neurons in the brain and brainstem, and stratified squamous epithelia of the esophagus, cervix and skin.

Post-translational modifications. Phosphorylated by TAK1/MAP3K7; this phosphorylation triggers association with BTRC and subsequent ubiquitination and degradation. Ubiquitinated in a BTRC-depdent manner; leading to degradation mediated through the proteasome pathway.

Domain organisation. The central region was initially thought to constitute a DED (death effector) domain. However, 3D-structure data reveal a previously uncharacterized fold that is different from the predicted fold of a DED (death effector) domain. It consists of a large, hydrophobic central cavity that is poised for cofactor binding.

Similarity. Belongs to the TNFAIP8 family. TNFAIP8L2 subfamily.

RefSeq proteins (1): NP_078851* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008477	TNFAIP8-like	Family
IPR038355	TNFAIP8_sf	Homologous_superfamily

Pfam: PF05527

UniProt features (14 total): helix 8, sequence conflict 2, chain 1, modified residue 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3F4M	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P589-F1	90.55	0.76

Functional residue map

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

Post-translational modifications (1): 3

Mutagenesis-validated functional residues (1):

Position	Phenotype
3	complete loss of interaction with btrc.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1483255	PI Metabolism

MSigDB gene sets: 141 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_169, GOBP_INFLAMMATORY_RESPONSE, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_NEGATIVE_REGULATION_OF_DEFENSE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_LEUKOCYTE_CELL_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE

GO Biological Process (6): T cell activation (GO:0042110), regulation of apoptotic process (GO:0042981), innate immune response (GO:0045087), negative regulation of inflammatory response (GO:0050728), negative regulation of T cell activation (GO:0050868), immune system process (GO:0002376)

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

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), lysosome (GO:0005764)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Phospholipid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lymphocyte activation	1
apoptotic process	1
regulation of programmed cell death	1
immune response	1
defense response to symbiont	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
T cell activation	1
regulation of T cell activation	1
negative regulation of lymphocyte activation	1
negative regulation of leukocyte cell-cell adhesion	1
biological_process	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
lytic vacuole	1

Protein interactions and networks

STRING

1046 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIPE2	CASP8	Q14790	760
TIPE2	TLR1	Q15399	496
TIPE2	FBXW5	Q969U6	442
TIPE2	JUN	P05412	440
TIPE2	FAS	P25445	423
TIPE2	TCHHL1	Q5QJ38	418
TIPE2	RPF2	Q9H7B2	394
TIPE2	RBM44	Q6ZP01	383
TIPE2	TNF	P01375	367
TIPE2	TESMIN	Q9Y4I5	347
TIPE2	ASPSCR1	Q9BZE9	333
TIPE2	TOM1	O60784	333
TIPE2	RGL1	Q9NZL6	329
TIPE2	ETV1	P50549	326
TIPE2	PCNP	Q8WW12	325

IntAct

13 interactions, top by confidence:

A	B	Type	Score
TNFAIP8L2	RAC1	psi-mi:“MI:0915”(physical association)	0.540
TNFAIP8L2	RAC1	psi-mi:“MI:0407”(direct interaction)	0.540
RAC1	TNFAIP8L2	psi-mi:“MI:0915”(physical association)	0.520
TNFAIP8L2	RAC1	psi-mi:“MI:0915”(physical association)	0.520
TNFAIP8L2	RAC2	psi-mi:“MI:0915”(physical association)	0.400
TNFAIP8L2	TES	psi-mi:“MI:0915”(physical association)	0.400
TNFAIP8L2	TES	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): TES (Affinity Capture-MS), AHNAK2 (Affinity Capture-MS), TNFAIP8L2 (Biochemical Activity), TES (Affinity Capture-MS), TNFAIP8L2 (Affinity Capture-Western), BTRC (Affinity Capture-Western), TES (Affinity Capture-MS), NPTN (Affinity Capture-MS), TNFAIP8L2 (Affinity Capture-Western), MAP3K7 (Affinity Capture-Western), TNFAIP8L2 (Reconstituted Complex), MAP3K7 (Reconstituted Complex), LINC00467 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0KI52, A0KW10, A1S7B2, A3M7G4, A3N0I5, A4SKR9, A5EVB5, A5W1G1, A6T2E3, A6W0E2, A7MFV3, A7MSW0, A8FUG8, A8GDD4, A8H5M2, A9X192, B0BPA5, B0KWC3, B0TQ01, B0VUD5, B1KID1, B2I9X7, B2KI57, B2SYW1, B3H1G2, B3R8A8, B4E5X9, B4EVG1, B7VH09, B8CLH3, C3JY69, C4L953, D4GGV4, D4HVG6, P22025, Q0K6N8, Q13U06, Q1LIP2, Q3IH15, Q3KA69

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

1 interactions.

A	Effect	B	Mechanism
MAP3K7	“down-regulates quantity by destabilization”	TNFAIP8L2	phosphorylation

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

257 predictions. Top by Δscore:

Variant	Effect	Δscore
1:151158691:A:AG	acceptor_gain	0.9800
1:151158692:G:GG	acceptor_gain	0.9800
1:151156720:CAGG:C	donor_loss	0.9700
1:151156721:AG:A	donor_loss	0.9700
1:151156723:GTGAG:G	donor_loss	0.9700
1:151156724:T:A	donor_loss	0.9700
1:151158689:CCA:C	acceptor_loss	0.9600
1:151156719:GCAG:G	donor_gain	0.9500
1:151160238:C:CT	acceptor_gain	0.9500
1:151160239:A:T	acceptor_gain	0.9400
1:151158664:A:AG	acceptor_gain	0.9300
1:151158665:G:GG	acceptor_gain	0.9300
1:151156699:C:T	donor_gain	0.9200
1:151158665:GT:G	acceptor_gain	0.8900
1:151156749:T:TA	donor_gain	0.8800
1:151156750:A:AA	donor_gain	0.8800
1:151158691:AG:A	acceptor_gain	0.8800
1:151158692:GG:G	acceptor_gain	0.8800
1:151156764:ATG:A	donor_gain	0.8400
1:151157492:GGTCC:G	donor_gain	0.8400
1:151158640:A:AC	acceptor_gain	0.8300
1:151158692:GGA:G	acceptor_gain	0.8000
1:151156723:G:GG	donor_gain	0.7900
1:151158692:GGACC:G	acceptor_gain	0.7900
1:151158692:GGAC:G	acceptor_gain	0.7700
1:151158665:GTGA:G	acceptor_gain	0.7400
1:151158665:GTGAC:G	acceptor_gain	0.7400
1:151157493:GTCC:G	donor_gain	0.7200
1:151157494:TCCT:T	donor_gain	0.7200
1:151157633:TTTG:T	donor_gain	0.7200

AlphaMissense

1195 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:151158904:G:C	K69N	0.990
1:151158904:G:T	K69N	0.990
1:151158892:A:C	K65N	0.989
1:151158892:A:T	K65N	0.989
1:151159007:T:C	F104L	0.989
1:151159009:T:A	F104L	0.989
1:151159009:T:G	F104L	0.989
1:151158891:A:T	K65I	0.987
1:151159022:T:C	F109L	0.987
1:151159024:C:A	F109L	0.987
1:151159024:C:G	F109L	0.987
1:151158890:A:G	K65E	0.982
1:151158902:A:G	K69E	0.981
1:151159004:A:C	S103R	0.979
1:151159006:C:A	S103R	0.979
1:151159006:C:G	S103R	0.979
1:151158885:T:C	L63P	0.978
1:151159028:T:C	F111L	0.978
1:151159030:C:A	F111L	0.978
1:151159030:C:G	F111L	0.978
1:151158800:A:C	S35R	0.974
1:151158802:C:A	S35R	0.974
1:151158802:C:G	S35R	0.974
1:151159136:T:C	F147L	0.974
1:151159138:T:A	F147L	0.974
1:151159138:T:G	F147L	0.974
1:151158986:G:C	G97R	0.972
1:151159122:G:C	R142P	0.972
1:151158864:C:A	A56D	0.971
1:151159121:C:A	R142S	0.970

dbSNP variants (sampled 300 via entrez): RS1000605489 (1:151158487 A>T), RS1002040275 (1:151156733 G>A), RS1003724418 (1:151154805 C>T), RS1005317606 (1:151156078 C>A,G), RS1005410822 (1:151155770 T>G), RS1005888525 (1:151157294 C>G,T), RS1006874130 (1:151156552 G>A,T), RS1006969202 (1:151156174 G>A), RS1007562820 (1:151155694 C>T), RS1007615190 (1:151155201 G>A), RS1007857188 (1:151158111 T>C,G), RS1007968414 (1:151157815 T>G), RS1008755745 (1:151159430 G>A), RS1008861513 (1:151159703 T>A,C), RS1009433536 (1:151156623 G>T)

Disease associations

OMIM: gene MIM:612112 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_38	Body mass index	4.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression, decreases expression	3
Acetaminophen	affects cotreatment, affects expression, increases expression	2
GSK-J4	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Diuron	decreases expression	1
Lipopolysaccharides	affects cotreatment, affects expression	1
Asbestos, Serpentine	increases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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