TIPRL

Summary

TIPRL (TOR signaling pathway regulator, HGNC:30231) is a protein-coding gene on chromosome 1q24.2, encoding TIP41-like protein (O75663). May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). It is a selective cancer dependency (DepMap: 40.6% of cell lines).

TIPRL is an inhibitory regulator of protein phosphatase-2A (PP2A) (see PPP2CA; MIM 176915), PP4 (see PPP4C; MIM 602035), and PP6 (see PPP6C; MIM 612725) (McConnell et al., 2007 [PubMed 17384681]).

Source: NCBI Gene 261726 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 35 total
• GTEx eGene: eQTL in 23 tissues, sQTL in 3 (q < 0.05)
• Cancer dependency (DepMap): dependent in 40.6% of screened cell lines
• Constraint (gnomAD): pLI 0.84 (intermediate), LOEUF 0.62 (unconstrained)
• MANE Select transcript: NM_152902

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30231
Approved symbol	TIPRL
Name	TOR signaling pathway regulator
Location	1q24.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC3794, dJ69E11.3, TIP41, TIPRL1
Ensembl gene	ENSG00000143155
Ensembl biotype	protein_coding
OMIM	611807
Entrez	261726

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 4 nonsense_mediated_decay

MANE Select: ENST00000367833

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2

ENST00000367833, ENST00000367830, ENST00000940324, ENST00000940325, ENST00000940326, ENST00001007338, ENST00001007340, ENST00001050131, ENST00001084698, ENST00001092160, ENST00001130066, ENST00001145310

RefSeq mRNA: 2 — MANE Select: NM_152902 NM_001031800, NM_152902

CCDS: CCDS1270, CCDS30935

Canonical transcript exons

ENST00000367833 — 7 exons

Exon	Start	End
ENSE00000958402	168183902	168184081
ENSE00000958403	168184779	168184878
ENSE00000958404	168191369	168191500
ENSE00001193861	168198919	168198981
ENSE00001193868	168196547	168196642
ENSE00001445713	168199903	168202109
ENSE00001445714	168178962	168179181

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 97.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.9554 / max 487.5155, expressed in 1822 samples.

Highest expression (Bgee): cauda epididymis, caput epididymis, tongue squamous epithelium, corpus epididymis, cortical plate.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TIPRL is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 26 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	1.6e-11	+0.14	1:168208381:G:A
Muscle Skeletal	eqtl	3.1e-10	-0.30	1:168207856:C:T
Whole Blood	eqtl	7.0e-09	-0.27	1:168153635:G:C
Pancreas	eqtl	1.3e-08	-0.24	1:168189928:A:G
Artery Tibial	eqtl	1.7e-08	+0.17	1:168207980:C:G
Testis	eqtl	2.7e-08	-0.26	1:168197378:C:T
Esophagus Mucosa	eqtl	5.0e-08	+0.20	1:168181334:C:G
Cells Cultured fibroblasts	eqtl	1.7e-07	+0.33	1:168153635:G:C
Skin Not Sun Exposed Suprapubic	eqtl	3.4e-07	+0.13	1:168185216:C:T
Esophagus Muscularis	eqtl	4.1e-07	+0.12	1:168205424:A:G
Thyroid	eqtl	1.0e-04	+0.16	1:168209059:C:T
Cells EBV-transformed lymphocytes	eqtl	1.3e-04	+0.22	1:168209059:C:T
Heart Left Ventricle	eqtl	4.7e-04	-0.21	1:168152068:A:G
Artery Aorta	eqtl	5.8e-04	+0.12	1:168175398:A:G
Brain Nucleus accumbens basal ganglia	sqtl	1.2e-03	-2.81	1:167914701:T:C
Esophagus Gastroesophageal Junction	eqtl	4.9e-03	+0.17	1:168131760:T:C
Prostate	eqtl	7.9e-03	-0.20	1:168129640:C:T
Brain Nucleus accumbens basal ganglia	eqtl	8.3e-03	+0.25	1:167604908:G:T
Brain Putamen basal ganglia	eqtl	1.3e-02	-1.36	1:167464240:C:T
Vagina	eqtl	1.8e-02	-0.20	1:167803261:G:A

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
6473	23.0984	1813
6474	10.2962	1774
6475	2.9543	1478
201805	0.6066	339

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	97.20	gold quality
caput epididymis	UBERON:0004358	95.64	gold quality
tongue squamous epithelium	UBERON:0006919	95.50	gold quality
corpus epididymis	UBERON:0004359	95.31	gold quality
cortical plate	UBERON:0005343	95.02	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.50	gold quality
nipple	UBERON:0002030	94.43	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.25	gold quality
saphenous vein	UBERON:0007318	93.90	gold quality
mammary duct	UBERON:0001765	93.73	gold quality
entorhinal cortex	UBERON:0002728	93.65	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.60	gold quality
hair follicle	UBERON:0002073	93.39	gold quality
colonic mucosa	UBERON:0000317	93.35	gold quality
epithelium of mammary gland	UBERON:0003244	93.14	gold quality
pylorus	UBERON:0001166	92.94	gold quality
vena cava	UBERON:0004087	92.92	gold quality
adrenal tissue	UBERON:0018303	92.87	gold quality
ganglionic eminence	UBERON:0004023	92.83	gold quality
pons	UBERON:0000988	92.19	gold quality
CA1 field of hippocampus	UBERON:0003881	92.17	silver quality
parietal lobe	UBERON:0001872	92.16	gold quality
gingiva	UBERON:0001828	92.15	gold quality
gingival epithelium	UBERON:0001949	92.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.13	gold quality
calcaneal tendon	UBERON:0003701	92.13	gold quality
cardia of stomach	UBERON:0001162	92.12	gold quality
seminal vesicle	UBERON:0000998	92.07	gold quality
superior surface of tongue	UBERON:0007371	92.03	gold quality
visceral pleura	UBERON:0002401	91.96	gold quality
postcentral gyrus	UBERON:0002581	91.85	gold quality
endometrium	UBERON:0001295	91.81	gold quality
cranial nerve II	UBERON:0000941	91.64	gold quality
tibia	UBERON:0000979	91.64	gold quality
biceps brachii	UBERON:0001507	91.49	gold quality
pericardium	UBERON:0002407	91.48	gold quality
trigeminal ganglion	UBERON:0001675	91.45	gold quality
ventral tegmental area	UBERON:0002691	91.39	gold quality
occipital lobe	UBERON:0002021	91.34	gold quality
primary visual cortex	UBERON:0002436	91.33	gold quality
trabecular bone tissue	UBERON:0002483	91.31	gold quality
superior frontal gyrus	UBERON:0002661	91.30	gold quality
ventricular zone	UBERON:0003053	91.18	gold quality
renal medulla	UBERON:0000362	91.13	gold quality
middle temporal gyrus	UBERON:0002771	91.01	gold quality
parietal pleura	UBERON:0002400	90.98	gold quality
orbitofrontal cortex	UBERON:0004167	90.95	gold quality
squamous epithelium	UBERON:0006914	90.94	gold quality
superior vestibular nucleus	UBERON:0007227	90.88	gold quality
islet of Langerhans	UBERON:0000006	90.82	gold quality
tongue	UBERON:0001723	90.44	gold quality
tendon	UBERON:0000043	90.27	gold quality
esophagus squamous epithelium	UBERON:0006920	90.01	gold quality
pharyngeal mucosa	UBERON:0000355	89.96	gold quality
rectum	UBERON:0001052	89.93	gold quality
palpebral conjunctiva	UBERON:0001812	89.93	gold quality
heart right ventricle	UBERON:0002080	89.85	gold quality
germinal epithelium of ovary	UBERON:0001304	89.74	gold quality
substantia nigra pars compacta	UBERON:0001965	89.73	gold quality
oviduct epithelium	UBERON:0004804	89.70	gold quality
epithelium of esophagus	UBERON:0001976	89.67	gold quality
pleura	UBERON:0000977	89.66	gold quality
jejunum	UBERON:0002115	89.63	gold quality
cartilage tissue	UBERON:0002418	89.59	gold quality
uterus	UBERON:0000995	89.54	gold quality
cervix squamous epithelium	UBERON:0006922	89.54	silver quality
Brodmann (1909) area 9	UBERON:0013540	89.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.42	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.37	gold quality
inferior vagus X ganglion	UBERON:0005363	89.29	gold quality
urethra	UBERON:0000057	89.22	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.22	gold quality
body of tongue	UBERON:0011876	89.11	gold quality
mammalian vulva	UBERON:0000997	88.99	gold quality
prefrontal cortex	UBERON:0000451	88.95	gold quality
monocyte	CL:0000576	88.93	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.92	gold quality
buccal mucosa cell	CL:0002336	88.82	gold quality
mammary gland	UBERON:0001911	88.82	gold quality
medial globus pallidus	UBERON:0002477	88.77	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.75	gold quality
thoracic mammary gland	UBERON:0005200	88.73	gold quality
myometrium	UBERON:0001296	88.72	gold quality
mononuclear cell	CL:0000842	88.71	gold quality
secondary oocyte	CL:0000655	88.64	gold quality
lymph node	UBERON:0000029	88.57	gold quality
cerebral cortex	UBERON:0000956	88.57	gold quality
leukocyte	CL:0000738	88.56	gold quality
gastrocnemius	UBERON:0001388	88.54	gold quality
fallopian tube	UBERON:0003889	88.52	gold quality
stromal cell of endometrium	CL:0002255	88.51	gold quality
muscle of leg	UBERON:0001383	88.50	gold quality
epithelium of nasopharynx	UBERON:0001951	88.50	gold quality
embryo	UBERON:0000922	88.49	gold quality
jejunal mucosa	UBERON:0000399	88.44	gold quality
dorsal root ganglion	UBERON:0000044	88.42	gold quality
globus pallidus	UBERON:0001875	88.42	gold quality
oral cavity	UBERON:0000167	88.39	gold quality
temporal lobe	UBERON:0001871	88.38	gold quality
smooth muscle tissue	UBERON:0001135	88.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.87

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebral cortex	tissue	40.2	medium
Motor cortex	tissue	40.2
Putamen	tissue	40.0
Somatosensory cortex	tissue	39.9
Occipital cortex	tissue	39.5
Hippocampal formation	tissue	39.0
Prefrontal cortex	tissue	37.6
Entorhinal cortex	tissue	37.5
Basal ganglia	tissue	36.6	medium
Retrosplenial and cingulate cortex	tissue	35.7
Temporal cortex	tissue	34.6
Postcentral gyrus	tissue	34.3
Ventral forebrain	tissue	34.1
Thalamus	tissue	33.3
Retrosplenial cortex	tissue	32.8
Septum	tissue	32.5
Bone marrow	tissue	31.5	high
Insular cortex	tissue	30.8
Cerebellum	tissue	30.5	medium
Pons	tissue	30.3
Midbrain	tissue	29.3
Superior colliculi	tissue	28.3
Thymus	tissue	28.1
Amygdala	tissue	25.9
Parathyroid gland	tissue	25.7	medium
Olfactory bulb	tissue	25.0
Locus coeruleus	tissue	24.0
Hypothalamus	tissue	23.9
Nucleus accumbens	tissue	23.4
Substantia nigra	tissue	23.1
Skeletal muscle	tissue	22.8	medium
Frontal cortex	tissue	22.8
Caudate putamen	tissue	22.2
Heart muscle	tissue	22.1	medium
Hippocampus	tissue	22.1	medium
Endometrium 1	tissue	21.7	medium
Tongue	tissue	21.6
Choroid plexus	tissue	21.3
Smooth muscle	tissue	21.2	low
Liver	tissue	21.0	low
Colon	tissue	20.8	high
Lymph node	tissue	20.7	high
Rectum	tissue	20.6	high
Periaqueductal gray	tissue	20.6
Ovary	tissue	19.9	medium
Medulla oblongata	tissue	19.7
Breast	tissue	19.6	high
Esophagus	tissue	18.7	high
Tonsil	tissue	18.7	medium
Appendix	tissue	18.5	medium
Duodenum	tissue	17.9	high
Spinal cord	tissue	17.6
Urinary bladder	tissue	17.5	medium
Small intestine	tissue	17.4	high
Prostate	tissue	17.2	medium
Testis	tissue	17.0	medium
Cervix	tissue	16.6	high
Kidney	tissue	16.6	medium
Placenta	tissue	16.4	medium
Seminal vesicle	tissue	16.3	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Dorsal hippocampus (39.0), Subiculum (37.2), Ventral hippocampus (32.1), Arcuate nucleus (29.4), Temporo-occipital transitional zone (29.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting TIPRL by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 103 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-202-5P	99.78	67.65	991

Functional genomics

gnomAD constraint: pLI 0.842, LOEUF 0.616, missense Z 1.37 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000367833 — one region, missense o/e 0.76. DepMap (CRISPR cell-line fitness): dependent in 40.6% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SK-MEL-24 (-2.141), Malme-3M (-1.943), HMY-1 (-1.767), DBTRG-05MG (-1.437), WM1799 (-1.43), UACC-62 (-1.422), COLO 205 (-1.386), Daoy (-1.368), Panc 05.04 (-1.348), SNU-601 (-1.324), VMRC-RCW (-1.31), 8505C (-1.262), WM983B (-1.247), COV362 (-1.164), SNU-478 (-1.161).

Literature-anchored findings (GeneRIF, showing 8)

• Data indicate that PP2A holoenzyme biogenesis and activity are controlled by five PP2A modulators, consisting of alpha4, PTPA, LCMT1, PME-1 and TIPRL1, which serve to prevent promiscuous phosphatase activity until the holoenzyme is completely assembled. (PMID:22443683)
• TIPRL is highly up-regulated in human HCC samples and cell lines, compared with noncancerous liver tissues. (PMID:22841785)
• Unlike yeast TIP41, TIPRL has a positive effect on mTORC1 signaling through the association with PP2Ac. (PMID:23892082)
• overexpression of TIPRL promotes phosphorylation of H2AX, and increases gamma-H2AX positive foci in response to DNA damage, whereas knockdown of TIPRL inhibits gamma-H2AX phosphorylation (PMID:26717153)
• MPC2 rs10489202 was genome-wide significantly associated with schizophrenia. The expression quantitative trait loci analysis in lymphoblastoid cell lines from East Asian donors revealed that MPC2 rs10489202 was specifically and significantly associated with the expression of TIPRL gene. (PMID:30087317)
• The positive correlation of TIPRL with LC3 and CD133 contributes to cancer aggressiveness: potential biomarkers for early liver cancer. (PMID:31727942)
• TIPRL potentiates survival of lung cancer by inducing autophagy through the eIF2alpha-ATF4 pathway. (PMID:31862913)
• TIPRL, a Potential Double-edge Molecule to be Targeted and Re-targeted Toward Cancer. (PMID:38888871)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tiprl	ENSDARG00000032353
mus_musculus	Tiprl	ENSMUSG00000040843
rattus_norvegicus	Tiprl	ENSRNOG00000003048
drosophila_melanogaster	CG9578	FBGN0031094
caenorhabditis_elegans		WBGENE00022803

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1915087) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal startle reflex	1
abnormal forebrain development	1
embryonic growth retardation	1
preweaning lethality, complete penetrance	1
embryonic lethality prior to tooth bud stage	1
decreased thigmotaxis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus tropicalis	Q5FW12	93.8%	Diamond
Xenopus laevis	Q6IRA8	93.8%	Diamond
Dictyostelium discoideum	Q54MI6	41.0%	Diamond
Saccharomyces cerevisiae S288C	Q12199	38.6%	Diamond
Arabidopsis thaliana	Q8VXY4	38.5%	Diamond
Schizosaccharomyces pombe 972h-	Q9USK5	34.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR1255B2	ncRNA	100313835
GPR161	protein-coding	23432
MPC2	protein-coding	25874
DCAF6	protein-coding	55827
SFT2D2	protein-coding	375035
TRP-AGG2-1	tRNA	100189019
ADCY10	protein-coding	55811
MPZL1	protein-coding	9019

Protein

Protein identifiers

TIP41-like protein — O75663 (reviewed: O75663)

Alternative names: Putative MAPK-activating protein PM10, Type 2A-interacting protein

All UniProt accessions (1): O75663

UniProt curated annotations — full annotation on UniProt →

Function. May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). Isoform 1 inhibits catalytic activity of the PP2A(D) core complex in vitro. The PP2A(C):TIPRL complex does not show phosphatase activity. Acts as a negative regulator of serine/threonine-protein phosphatase 4 probably by inhibiting the formation of the active PPP4C:PPP4R2 complex; the function is proposed to implicate it in DNA damage response by promoting H2AX phosphorylated on Ser-140 (gamma-H2AX). May play a role in the regulation of ATM/ATR signaling pathway controlling DNA replication and repair.

Subunit / interactions. Isoform 1 interacts with PPP2CA. Isoform 2 does not interact with PPP2CA. Interacts with PPP2CB, PPP4C and PPP6C. Interacts with IGBP1; the interaction is dependent on PPP2CA. Associates with a protein phosphatase 2A PP2A(C):IGBP1 complex. Interacts with PPP4C and PPP4R2.

Subcellular location. Cytoplasm.

Similarity. Belongs to the TIP41 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75663-1	1	yes
O75663-2	2, TIP_i2

RefSeq proteins (2): NP_001026970, NP_690866* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007303	TIP41-like	Family
IPR051330	Phosphatase_reg/MetRdx	Family

Pfam: PF04176

UniProt features (35 total): strand 12, helix 10, mutagenesis site 5, modified residue 2, turn 2, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
5D9G	Crystal structure of TIPRL, TOR signaling pathway regulator-like, in complex with peptide	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75663-F1	85.04	0.71

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH approved · IF approved

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 (2)

Type	Positions
N6-acetyllysine	106
Phosphoserine	265

Mutagenesis-validated functional residues (5)

Position	Phenotype
198	abolishes interaction with ppp2ca, ppp2cb and ppp4c.
71	abolishes interaction with ppp2ca, ppp2cb and ppp4c.
79	diminishes interaction with ppp2ca.
136	abolishes interaction with ppp2ca, ppp2cb and ppp4c.
196	abolishes interaction with ppp2ca, ppp2cb and ppp4c.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 151 (showing top): ATF_B, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, CREBP1_Q2, SP1_Q2_01, CREB_Q4, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_DNA_DAMAGE_RESPONSE, ATF3_Q6, CREB_Q2_01, ATF4_Q2, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_TOR_SIGNALING

GO Biological Process (2): DNA damage checkpoint signaling (GO:0000077), TOR signaling (GO:0031929)

GO Molecular Function (3): protein phosphatase inhibitor activity (GO:0004864), protein phosphatase activator activity (GO:0072542), protein binding (GO:0005515)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

11 GO namespaces:

Category	Terms
phosphoprotein phosphatase activity	2
protein phosphatase regulator activity	2
cellular anatomical structure	2
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
intracellular signal transduction	1
phosphatase inhibitor activity	1
phosphatase activator activity	1
binding	1
cytoplasm	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 7 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
DNA damage checkpoint signaling	BP	mutant phenotype
protein phosphatase inhibitor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,416 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIPRL	PPP6C	O00743	874
TIPRL	PPP4C	P33172	821
TIPRL	IGBP1	P78318	775
TIPRL	PPP2CA	P05323	771
TIPRL	LCMT1	Q9UIC8	697
TIPRL	PPME1	Q9Y570	651
TIPRL	PTPA	Q15257	612
TIPRL	TBCEL	Q5QJ74	535
TIPRL	TUB	P50607	502
TIPRL	ATM	Q13315	485
TIPRL	PPP6R1	Q9UPN7	418
TIPRL	PDRG1	Q9NUG6	414
TIPRL	MAP2K7	O14733	405
TIPRL	PPP2R1A	P30153	390
TIPRL	NACA2	Q9H009	389

IntAct

Human interaction partners of TIPRL in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

12 partners by confidence:

Partner	Interaction type	MIscore	Records
PPP4C	association	0.850	5
PPP4R2	association	0.800	2
PPP6C	direct interaction	0.700	2
PPP2CA	physical association	0.590	9
PPP2CB	direct interaction	0.590	1
DYNLT2B	association	0.510	2
IGBP1	physical association	0.400	2
AQP12B	association	0.350	1
FASLG	association	0.350	1
FUCA1	association	0.350	1
PTPN18	association	0.350	1
DYNLT1	physical association	0.000	1

BioGRID (161 interactions; top human partners by supporting records): PPP4R2 (Affinity Capture-MS; 5 records), PPP4C (Affinity Capture-MS; 4 records), PPP6C (Affinity Capture-MS; 4 records), IGBP1 (Affinity Capture-Western; 3 records), PPP2CB (Co-fractionation; 3 records), PPP2R1A (Affinity Capture-MS; 3 records), ATP6V1A (Co-fractionation; 2 records), AURKA (Affinity Capture-MS; 2 records), CCNF (Affinity Capture-MS; 2 records), FUCA1 (Affinity Capture-MS; 2 records), HUWE1 (Affinity Capture-MS; 2 records), ITLN1 (Affinity Capture-MS; 2 records), PARK2 (Proximity Label-MS; 2 records), PPP2CA (Affinity Capture-Western; 2 records), PTPDC1 (Affinity Capture-MS; 2 records)

Disease & clinical

Genetic variants

Variant evidence for TIPRL: 35 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 676):

Position(s)	Effect	Δscore	Sites
1:168184768	acceptor_gain	1.0000
1:168191367–168191368	acceptor_loss	1.0000	6
1:168191501	donor_loss	1.0000	2
1:168196545–168196546	acceptor_loss	1.0000	6
1:168196643–168196644	donor_loss	1.0000	4
1:168179182–168179183	donor_loss	0.9900	3
1:168184769	acceptor_gain	0.9900
1:168184773	acceptor_gain	0.9900
1:168191502	donor_loss	0.9900
1:168196643	donor_loss	0.9900

AlphaMissense

802 missense substitutions predicted likely pathogenic (of 1,816 scored), across 179 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M48	9	0.987	0.999
M175	9	0.967	0.997
D162	8	0.999	1.000
D158	8	0.997	0.999
D190	8	0.994	0.999
D109	8	0.991	0.997
F50	8	0.973	1.000
H161	8	0.968	0.990
D198	8	0.963	0.996
F67	8	0.960	0.999
H163	8	0.904	0.998
H26	8	0.879	0.982
W110	7	0.999	1.000
F156	7	0.996	0.998
W91	7	0.995	1.000
E159	7	0.995	0.999
W18	7	0.992	0.999
E157	7	0.988	0.997
N53	7	0.981	0.999
E47	7	0.978	0.996

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	0.000232
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.00076

Disease associations

OMIM: gene MIM:611807 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST90002404_34	Red cell distribution width	6e-21
GCST011741_40	LDL cholesterol levels in HIV infection	8e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067004 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

1 potent at pChembl≥5 of 2 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.16	Kd	7005	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149592: Binding affinity to human TIPRL incubated for 45 mins by Kinobead based pull down assay	kd	7.0055	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, increases methylation, decreases expression	5
sodium arsenite	affects binding, increases reaction, affects cotreatment, increases abundance, increases expression	2
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
sodium arsenate	increases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, increases reaction	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	increases expression	1
bisphenol AF	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, affects expression	1
Air Pollutants, Occupational	affects expression	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Cisplatin	increases expression, decreases response to substance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652634	Binding	Binding affinity to human TIPRL incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3JA	Abcam HEK293T TIPRL KO	Transformed cell line	Female
CVCL_TS42	HAP1 TIPRL (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TIPRL across ~30M SureChEMBL compounds — explore on Sugi Predict.