TIPE1

Summary

TIPE1 (TNF alpha induced protein 8 like 1, HGNC:28279) is a protein-coding gene on chromosome 19p13.3, encoding Tumor necrosis factor alpha-induced protein 8-like protein 1 (Q8WVP5). Acts as a negative regulator of mTOR activity.

Enables identical protein binding activity. Predicted to be involved in negative regulation of TOR signaling. Predicted to be active in cytoplasm.

Source: NCBI Gene 126282 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_152362

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28279
Approved symbol	TIPE1
Name	TNF alpha induced protein 8 like 1
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC17791
Ensembl gene	ENSG00000185361
Ensembl biotype	protein_coding
OMIM	615869
Entrez	126282

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000327473, ENST00000536716, ENST00000598107, ENST00000883935, ENST00000883936, ENST00000883937, ENST00000961763

RefSeq mRNA: 2 — MANE Select: NM_152362 NM_001167942, NM_152362

CCDS: CCDS12132

Canonical transcript exons

ENST00000327473 — 2 exons

Exon	Start	End
ENSE00001326039	4651867	4655568
ENSE00001406196	4639516	4639629

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 97.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.3774 / max 92.7286, expressed in 1370 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173365	4.1781	1354
173366	0.1993	95

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	97.49	gold quality
bronchus	UBERON:0002185	96.16	gold quality
oviduct epithelium	UBERON:0004804	93.64	gold quality
right uterine tube	UBERON:0001302	91.20	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.18	gold quality
endothelial cell	CL:0000115	89.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.45	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.78	gold quality
right lobe of liver	UBERON:0001114	87.42	gold quality
liver	UBERON:0002107	86.78	gold quality
fallopian tube	UBERON:0003889	84.97	gold quality
ileal mucosa	UBERON:0000331	84.82	gold quality
kidney epithelium	UBERON:0004819	83.16	gold quality
epithelium of nasopharynx	UBERON:0001951	82.08	gold quality
caput epididymis	UBERON:0004358	81.85	gold quality
spleen	UBERON:0002106	81.78	gold quality
apex of heart	UBERON:0002098	81.05	gold quality
Brodmann (1909) area 23	UBERON:0013554	80.85	gold quality
right frontal lobe	UBERON:0002810	80.57	gold quality
Brodmann (1909) area 46	UBERON:0006483	80.50	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.46	gold quality
nasal cavity epithelium	UBERON:0005384	80.45	gold quality
prefrontal cortex	UBERON:0000451	80.37	gold quality
colon	UBERON:0001155	79.88	gold quality
monocyte	CL:0000576	79.59	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.55	gold quality
leukocyte	CL:0000738	79.54	gold quality
transverse colon	UBERON:0001157	79.36	gold quality
large intestine	UBERON:0000059	79.34	gold quality
frontal cortex	UBERON:0001870	79.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

96 targeting TIPE1, 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-3120-5P	100.00	65.56	965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311

Literature-anchored findings (GeneRIF, showing 19)

• high levels of TIPE1 (TNFAIP8-like 1) mRNA were detected in most human carcinoma cell lines, especially in cells transformed with viral genomes (PMID:21600655)
• oxidative stress induces Tnfaip8 l1/Oxi-beta, which results in increased autophagy by its exclusive binding with FBXW5 to stabilize TSC2 (PMID:24444419)
• TIPE1 induced apoptosis in HCC cells by negatively regulating Rac1 pathway (PMID:25043299)
• the levels of TIPE1 were significantly reduced and inversely correlated with differentiation status and distant metastasis in primary gastric cancer tissues. (PMID:28994231)
• our results demonstrate the anti-tumor role of TIPE1 in osteosarcoma (PMID:30062520)
• High TIPE1 expression is associated with repression of p53 acetylation and cervical cancer. (PMID:30445600)
• TIPE1 impairs stemness maintenance in colorectal cancer through directly targeting beta-catenin. (PMID:31111874)
• TNFAIP8L1 and FLT1 polymorphisms alter the susceptibility to cervical cancer amongst uyghur females in China. (PMID:31289124)
• These results suggested that TIPE1 might suppress the invasion and migration of breast cancer cells and inhibit epithelial-to-mesenchymal transition primarily via the ERK signaling pathway. (PMID:31559412)
• Excessive ROS induced by the overexpression of TIPE1 in endothelial cells accelerated the process of atherogenesis. (PMID:31672550)
• CDKN3 regulates cisplatin resistance to colorectal cancer through TIPE1. (PMID:32329836)
• TIPE1-mediated autophagy suppression promotes nasopharyngeal carcinoma cell proliferation via the AMPK/mTOR signalling pathway. (PMID:32588529)
• TIPE-mediated up-regulation of MMP-9 promotes colorectal cancer invasion and metastasis through MKK-3/p38/NF-kappaB pro-oncogenic signaling pathway. (PMID:32843639)
• TNF-alpha-Induce Protein 8-Like 1 Inhibits Hepatic Steatosis, Inflammation, and Fibrosis by Suppressing Polyubiquitination of Apoptosis Signal-Regulating Kinase 1. (PMID:33713358)
• Human tumor necrosis factor alpha-induced protein eight-like 1 exhibited potent anti-tumor effect through modulation of proliferation, survival, migration and invasion of lung cancer cells. (PMID:33895911)
• Phosphoinositide-Binding Protein TIPE1 Promotes Alternative Activation of Macrophages and Tumor Progression via PIP3/Akt/TGFbeta Axis. (PMID:35135809)
• TIPE1 inhibits osteosarcoma tumorigenesis and progression by regulating PRMT1 mediated STAT3 arginine methylation. (PMID:36151091)
• TIPE1 inhibits the growth of Ewing’s sarcoma cells by suppressing Wnt/beta-catenin signaling. (PMID:36495466)
• A pan-cancer analysis of TNFAIP8L1 in human tumors. (PMID:38065896)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tnfaip8l1	ENSDARG00000086457
mus_musculus	Tnfaip8l1	ENSMUSG00000044469
rattus_norvegicus	Tnfaip8l1	ENSRNOG00000069635
drosophila_melanogaster	sigmar	FBGN0034894

Paralogs (3): TNFAIP8 (ENSG00000145779), TNFAIP8L2 (ENSG00000163154), TNFAIP8L3 (ENSG00000183578)

Protein

Protein identifiers

Tumor necrosis factor alpha-induced protein 8-like protein 1 — Q8WVP5 (reviewed: Q8WVP5)

Alternative names: Oxidative stress-regulated gene-beta

All UniProt accessions (1): Q8WVP5

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a negative regulator of mTOR activity.

Subunit / interactions. Interacts with FBXW5; TNFAIP8L1 competes with TSC2 to bind FBXW5 increasing TSC2 stability by preventing its ubiquitination.

Subcellular location. Cytoplasm.

Tissue specificity. High expression detected in most carcinoma cell lines, especially in cells transformed with virus genomes.

Induction. Up-regulated by oxidative stress (OS) at both transcriptional and translational levels.

Similarity. Belongs to the TNFAIP8 family.

RefSeq proteins (2): NP_001161414, NP_689575* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008477	TNFAIP8-like	Family
IPR038355	TNFAIP8_sf	Homologous_superfamily

Pfam: PF05527

UniProt features (2 total): chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVP5-F1	91.20	0.76

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1483255	PI Metabolism

MSigDB gene sets: 175 (showing top): MYOGENIN_Q6, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, FISCHER_G2_M_CELL_CYCLE, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_NEGATIVE_REGULATION_OF_TOR_SIGNALING, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS, AACTTT_UNKNOWN, GOBP_TOR_SIGNALING, USF_02, MARSON_BOUND_BY_E2F4_UNSTIMULATED, chr19p13, NUYTTEN_NIPP1_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_DN, WHITFIELD_CELL_CYCLE_G2_M, OHGUCHI_LIVER_HNF4A_TARGETS_DN

GO Biological Process (2): negative regulation of TOR signaling (GO:0032007), regulation of apoptotic process (GO:0042981)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

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
TOR signaling	1
regulation of TOR signaling	1
negative regulation of intracellular signal transduction	1
apoptotic process	1
regulation of programmed cell death	1
protein binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIPE1	POMP	Q9Y244	649
TIPE1	SPMIP2	Q96LM5	500
TIPE1	FBXW5	Q969U6	485
TIPE1	CASP10	Q92851	470
TIPE1	PPP1R14C	Q8TAE6	445
TIPE1	PRTFDC1	Q9NRG1	428
TIPE1	PGM2L1	Q6PCE3	382
TIPE1	DNAJC1	Q96KC8	349
TIPE1	SMIM3	Q9BZL3	343
TIPE1	TMEM40	Q8WWA1	315
TIPE1	GPRIN1	Q7Z2K8	307
TIPE1	SMIM12	Q96EX1	298
TIPE1	TNFAIP2	Q03169	292
TIPE1	TINAGL1	Q9GZM7	282
TIPE1	KLF10	Q13118	280

IntAct

48 interactions, top by confidence:

A	B	Type	Score
TNFAIP8L1	PSME3	psi-mi:“MI:0915”(physical association)	0.720
PSME3	TNFAIP8L1	psi-mi:“MI:0915”(physical association)	0.720
TNFAIP8L1	DVL3	psi-mi:“MI:0915”(physical association)	0.670
DVL3	TNFAIP8L1	psi-mi:“MI:0915”(physical association)	0.670
EVI5	TNFAIP8L1	psi-mi:“MI:0915”(physical association)	0.560
CAVIN1	TNFAIP8L1	psi-mi:“MI:0915”(physical association)	0.560
TNFAIP8L1	STAC3	psi-mi:“MI:0915”(physical association)	0.560
TNFAIP8L1	MED4	psi-mi:“MI:0915”(physical association)	0.560
SNRPA	TNFAIP8L1	psi-mi:“MI:0915”(physical association)	0.560
TNFAIP8L1	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
ANKRD36B	TNFAIP8L1	psi-mi:“MI:0915”(physical association)	0.560
RPL9	TNFAIP8L1	psi-mi:“MI:0915”(physical association)	0.560
ZRSR2	TNFAIP8L1	psi-mi:“MI:0915”(physical association)	0.560
TNFAIP8L1	TNFAIP8L1	psi-mi:“MI:0915”(physical association)	0.560
KLK6	TNFAIP8L1	psi-mi:“MI:0915”(physical association)	0.560
TNFAIP8L1	EVI5	psi-mi:“MI:0915”(physical association)	0.000
TNFAIP8L1	PSME3	psi-mi:“MI:0915”(physical association)	0.000
TNFAIP8L1	DVL3	psi-mi:“MI:0915”(physical association)	0.000
TNFAIP8L1	CAVIN1	psi-mi:“MI:0915”(physical association)	0.000
TNFAIP8L1	STAC3	psi-mi:“MI:0915”(physical association)	0.000
TNFAIP8L1	MED4	psi-mi:“MI:0915”(physical association)	0.000
RPL9	TNFAIP8L1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (61): TNFAIP8L1 (Two-hybrid), TNFAIP8L1 (Two-hybrid), TNFAIP8L1 (Two-hybrid), TNFAIP8L1 (Two-hybrid), TNFAIP8L1 (Two-hybrid), TNFAIP8L1 (Two-hybrid), TNFAIP8L1 (Two-hybrid), TNFAIP8L1 (Two-hybrid), TNFAIP8L1 (Two-hybrid), TNFAIP8L1 (Two-hybrid), TNFAIP8L1 (Two-hybrid), TNFAIP8L1 (Two-hybrid), STAC3 (Two-hybrid), ANKRD36B (Two-hybrid), TNFAIP8L1 (Affinity Capture-Western)

ESM2 similar proteins: A1JU75, A2BTD8, A2BYT7, A2C500, A2CC26, A5GIU6, A5GVV9, A9BCP8, B0CA85, B0RN90, B1X509, B1XK97, B2FKA7, B2ITQ6, B7KEE5, B8HUU1, C1DNP6, P03179, P15443, P29580, P74069, Q00098, Q02MM2, Q110A6, Q1HVJ0, Q1RE32, Q2JIJ7, Q2JVL1, Q318I3, Q31L05, Q3AMM9, Q3AUW5, Q3BY37, Q3KSV4, Q3MFC2, Q46IQ8, Q4H4F7, Q4UZ69, Q5N0W6, Q6GZV2

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

331 predictions. Top by Δscore:

Variant	Effect	Δscore
19:4639622:GAGA:G	donor_gain	1.0000
19:4639624:GA:G	donor_gain	1.0000
19:4639626:GTAG:G	donor_gain	1.0000
19:4639627:TAGGT:T	donor_loss	1.0000
19:4639628:AGGT:A	donor_loss	1.0000
19:4639630:G:GG	donor_gain	0.9900
19:4639631:T:A	donor_loss	0.9900
19:4651861:CCGCA:C	acceptor_loss	0.9900
19:4651862:CGCA:C	acceptor_loss	0.9900
19:4651863:GCA:G	acceptor_loss	0.9900
19:4651864:CAGGC:C	acceptor_loss	0.9900
19:4651866:G:GA	acceptor_loss	0.9900
19:4651865:A:AG	acceptor_gain	0.9800
19:4651866:G:GG	acceptor_gain	0.9800
19:4651866:GGCC:G	acceptor_gain	0.9800
19:4639627:TAG:T	donor_gain	0.9700
19:4651865:AG:A	acceptor_gain	0.9700
19:4651866:GG:G	acceptor_gain	0.9700
19:4639600:TTGG:T	donor_gain	0.9600
19:4651866:GGCCA:G	acceptor_gain	0.9600
19:4651862:C:CA	acceptor_gain	0.9500
19:4651866:GGC:G	acceptor_gain	0.9400
19:4639603:G:GT	donor_gain	0.9300
19:4639605:C:G	donor_gain	0.9300
19:4639623:AGA:A	donor_gain	0.8700
19:4639624:GAG:G	donor_gain	0.8700
19:4639623:A:T	donor_gain	0.8200
19:4639628:AG:A	donor_gain	0.8100
19:4639629:GG:G	donor_gain	0.8100
19:4639611:G:T	donor_gain	0.7800

AlphaMissense

1199 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:4652200:T:C	F111L	0.990
19:4652202:C:A	F111L	0.990
19:4652202:C:G	F111L	0.990
19:4652179:T:C	F104L	0.985
19:4652181:C:A	F104L	0.985
19:4652181:C:G	F104L	0.985
19:4652014:T:C	F49L	0.979
19:4652016:C:A	F49L	0.979
19:4652016:C:G	F49L	0.979
19:4652176:A:C	S103R	0.977
19:4652178:C:A	S103R	0.977
19:4652178:C:G	S103R	0.977
19:4652194:T:C	F109L	0.976
19:4652196:C:A	F109L	0.976
19:4652196:C:G	F109L	0.976
19:4652064:G:C	K65N	0.975
19:4652064:G:T	K65N	0.975
19:4652076:G:C	K69N	0.971
19:4652076:G:T	K69N	0.971
19:4652171:C:A	A101D	0.971
19:4652180:T:C	F104S	0.965
19:4652308:T:C	F147L	0.963
19:4652310:C:A	F147L	0.963
19:4652310:C:G	F147L	0.963
19:4652333:T:C	F155S	0.963
19:4652179:T:A	F104I	0.958
19:4652198:C:T	T110I	0.956
19:4652200:T:A	F111I	0.956
19:4652293:C:A	R142S	0.956
19:4652074:A:G	K69E	0.954

dbSNP variants (sampled 300 via entrez): RS1000104733 (19:4654493 G>A,C,T), RS1000156642 (19:4646409 G>T), RS1000217020 (19:4648893 C>T), RS1000407400 (19:4654288 G>A), RS1000651111 (19:4650209 G>T), RS1000710069 (19:4644771 T>G), RS1000741583 (19:4655342 C>T), RS1000762538 (19:4644993 C>G), RS1000835637 (19:4650503 A>AAGG), RS1000912596 (19:4639056 A>G), RS1001011261 (19:4645658 C>T), RS1001309767 (19:4651519 C>G), RS1001384931 (19:4641139 G>A), RS1001403333 (19:4642278 C>G,T), RS1001429492 (19:4642546 G>A)

Disease associations

OMIM: gene MIM:615869 | 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: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	3
trichostatin A	affects expression, increases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Smoke	increases abundance, increases expression, decreases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
kojic acid	decreases expression	1
3,4-dichloroaniline	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	increases reaction, affects binding	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
diallyl trisulfide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
entinostat	increases expression	1
abrine	decreases expression	1
NSC 689534	affects binding, decreases expression	1
NSC668394	decreases expression	1
Bortezomib	decreases expression, increases response to substance	1
Resveratrol	affects cotreatment, decreases expression, increases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Biological Factors	decreases expression	1

Clinical trials (associated diseases)

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