TNS1

Summary

TNS1 (tensin 1, HGNC:11973) is a protein-coding gene on chromosome 2q35, encoding Tensin-1 (Q9HBL0). May act as a protein phosphatase and/or a lipid phosphatase.

The protein encoded by this gene localizes to focal adhesions, regions of the plasma membrane where the cell attaches to the extracellular matrix. This protein crosslinks actin filaments and contains a Src homology 2 (SH2) domain, which is often found in molecules involved in signal transduction. This protein is a substrate of calpain II. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 7145 — RefSeq curated summary.

At a glance

• GWAS associations: 55
• Clinical variants (ClinVar): 406 total
• MANE Select transcript: NM_001387777

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11973
Approved symbol	TNS1
Name	tensin 1
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp586K0617, PPP1R155
Ensembl gene	ENSG00000079308
Ensembl biotype	protein_coding
OMIM	600076
Entrez	7145

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 17 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000171887, ENST00000310858, ENST00000413280, ENST00000413554, ENST00000419504, ENST00000423413, ENST00000439083, ENST00000446688, ENST00000446903, ENST00000449814, ENST00000453356, ENST00000465306, ENST00000479185, ENST00000480416, ENST00000480665, ENST00000490566, ENST00000492338, ENST00000495556, ENST00000615025, ENST00000646520, ENST00000649572, ENST00000651849, ENST00000682258, ENST00000705226

RefSeq mRNA: 4 — MANE Select: NM_001387777 NM_001308022, NM_001308023, NM_001387777, NM_022648

CCDS: CCDS2407, CCDS77528, CCDS77529, CCDS92941

Canonical transcript exons

ENST00000682258 — 33 exons

Exon	Start	End
ENSE00000785630	217813685	217813816
ENSE00000785633	217880898	217881014
ENSE00000785634	217882346	217882411
ENSE00000785636	217885744	217885819
ENSE00000785637	217886044	217886104
ENSE00000785638	217886534	217886646
ENSE00000785639	217890962	217891045
ENSE00000796867	217814912	217814998
ENSE00000796868	217817690	217818759
ENSE00000796869	217847510	217849087
ENSE00000934759	217821740	217821938
ENSE00000934761	217831455	217831547
ENSE00000934762	217835091	217835166
ENSE00000934763	217836015	217836211
ENSE00001592528	217990942	217991056
ENSE00001650791	217978765	217978802
ENSE00001805211	218002840	218002995
ENSE00003475068	217906335	217906385
ENSE00003505979	217810248	217810319
ENSE00003511190	217900463	217900512
ENSE00003528528	217897798	217897969
ENSE00003539997	217808075	217808107
ENSE00003560462	217893439	217893561
ENSE00003617900	217813215	217813307
ENSE00003622181	217920195	217920236
ENSE00003667007	217885035	217885164
ENSE00003671574	217907210	217907251
ENSE00003674029	217895006	217895056
ENSE00003674842	217809823	217809991
ENSE00003676153	217812368	217812445
ENSE00003678526	217808603	217808671
ENSE00003686279	217892948	217893012
ENSE00003922069	217799791	217804603

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.3907 / max 963.4577, expressed in 1462 samples.

FANTOM5 promoters (30 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33905	14.9840	968
33917	6.5337	735
33882	3.4444	412
33877	3.0138	97
33909	1.6692	426
33892	1.6610	396
33896	1.5102	231
33920	1.4649	673
33910	0.3949	164
33870	0.2572	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	99.84	gold quality
saphenous vein	UBERON:0007318	99.84	gold quality
urethra	UBERON:0000057	99.66	gold quality
cauda epididymis	UBERON:0004360	99.59	gold quality
lower lobe of lung	UBERON:0008949	99.58	gold quality
seminal vesicle	UBERON:0000998	99.57	gold quality
left ventricle myocardium	UBERON:0006566	99.50	gold quality
right coronary artery	UBERON:0001625	99.47	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.47	gold quality
popliteal artery	UBERON:0002250	99.45	gold quality
tibial artery	UBERON:0007610	99.45	gold quality
nipple	UBERON:0002030	99.43	gold quality
visceral pleura	UBERON:0002401	99.43	gold quality
aorta	UBERON:0000947	99.40	gold quality
descending thoracic aorta	UBERON:0002345	99.40	gold quality
mucosa of stomach	UBERON:0001199	99.38	gold quality
thoracic aorta	UBERON:0001515	99.34	gold quality
ascending aorta	UBERON:0001496	99.32	gold quality
synovial joint	UBERON:0002217	99.32	gold quality
renal medulla	UBERON:0000362	99.30	gold quality
superficial temporal artery	UBERON:0001614	99.26	gold quality
vena cava	UBERON:0004087	99.24	gold quality
dorsal root ganglion	UBERON:0000044	99.21	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.19	gold quality
colonic epithelium	UBERON:0000397	99.18	gold quality
coronary artery	UBERON:0001621	99.17	gold quality
lower esophagus	UBERON:0013473	99.16	gold quality
left coronary artery	UBERON:0001626	99.11	gold quality
mammary duct	UBERON:0001765	99.11	gold quality
trigeminal ganglion	UBERON:0001675	99.06	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	49.03
E-CURD-119	yes	48.06
E-GEOD-134144	yes	31.74
E-GEOD-135922	yes	27.86
E-MTAB-6678	yes	26.60
E-MTAB-8410	yes	23.99
E-GEOD-81608	yes	15.79
E-MTAB-9221	yes	11.86
E-HCAD-25	yes	5.19
E-GEOD-124858	no	206.90
E-MTAB-9067	no	4.10
E-MTAB-9467	no	1.43
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

208 targeting TNS1, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-141-3P	99.94	72.79	2421

Literature-anchored findings (GeneRIF, showing 23)

• Tensin may play important roles in mesangial ECM production through an adhesion complex with integrin alpha5, FAK, and vinculin. (PMID:14991332)
• Results suggest that the protein-tyrosine phosphatase domain of tensin exhibits isoform-specific association with PP1alpha in a restricted spatial region of adhesions that are formed during cell migration. (PMID:17435217)
• Aged fibroblasts, generated with the Hayflick replicative senescence model, exhibit as siRNA silences fibroblasts, a reduced tensin1 expression and an impaired gel contraction capacity. (PMID:18537817)
• Tensins may represent a novel group of metastasis suppressors in the kidney, the loss of which leads to greater tumor cell motility and consequent metastasis. (PMID:19194507)
• The expression of tensin is increased in mesangial cells with stimulating of high concentrations of glucose. (PMID:19664390)
• Results suggest that PP1alpha bound to tensin1 has effects in reducing migration and invasion that are not mediated through DLC-1, and show the importance of PP1alpha binding to tensin1 for the regulation of cell polarization, migration, and invasion. (PMID:19826001)
• Data show expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in lung tissue and indicate potential targets for interventions to alleviate respiratory disease. (PMID:20010834)
• data demonstrate that tensin1 is extensively phosphorylated on Ser/Thr residues in cells and phosphorylation by p38 MAPK regulates the specificity of the tensin1 Src homology 2 domain for binding to different proteins (PMID:20798394)
• TNS1 polymorphism associated with COPD risk and lung function decline (PMID:21965014)
• TNS1, MET, and TRKC tyrosine-phosphorylated proteins are upregulated during epithelial-mesenchymal transition induced with TGF-beta, and predict the outcome in lung adenocarcinoma patients. (PMID:26216473)
• miR-548j functions as a metastasis-promoting miRNA to regulate breast cancer cell invasion and metastasis by targeting Tensin1 and activating Cdc42. (PMID:26949125)
• TNS1 plays an essential role in TGF-beta-induced myofibroblast differentiation. (PMID:28005397)
• Hic-5 is a crucial regulator of extracellular matrix remodeling in Cancer-associated fibroblasts by promoting fibrillar adhesion formation through a novel interaction with tensin1. (PMID:29348458)
• Hyperactivity of Mek in TNS1 knockouts leads to potential treatments for cystic kidney diseases. (PMID:31740667)
• Tensin1 expression and function in chronic obstructive pulmonary disease. (PMID:31831813)
• LncRNA MAGI2-AS3 inhibits bladder cancer progression by targeting the miR-31-5p/TNS1 axis. (PMID:33231563)
• miR-152/TNS1 axis inhibits non-small cell lung cancer progression through Akt/mTOR/RhoA pathway. (PMID:33269380)
• MaTAR25 lncRNA regulates the Tensin1 gene to impact breast cancer progression. (PMID:33353933)
• Tensin 1 (TNS1) is a modifier gene for low body mass index (BMI) in homozygous [F508del]CFTR patients. (PMID:34086412)
• miR-31-5p modulates cell progression in lung adenocarcinoma through TNS1/p53 axis. (PMID:35037949)
• Tensin Regulates Fundamental Biological Processes by Interacting with Integrins of Tonsil-Derived Mesenchymal Stem Cells. (PMID:35954177)
• lncRNA ZNRD1-AS1 promotes malignant lung cell proliferation, migration, and angiogenesis via the miR-942/TNS1 axis and is positively regulated by the m[6]A reader YTHDC2. (PMID:36581942)
• Tensin 1 regulated by hepatic leukemia factor represses the progression of prostate cancer. (PMID:37712764)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tns1b	ENSDARG00000020845
mus_musculus	Tns1	ENSMUSG00000055322
rattus_norvegicus	Tns1	ENSRNOG00000014182

Paralogs (6): HVCN1 (ENSG00000122986), TPTE2 (ENSG00000132958), TNS3 (ENSG00000136205), TMEM266 (ENSG00000169758), PTEN (ENSG00000171862), TPTE (ENSG00000274391)

Protein

Protein identifiers

Tensin-1 — Q9HBL0 (reviewed: Q9HBL0)

All UniProt accessions (15): Q9HBL0, A0A2R8Y4T1, A0A3B3IRK7, A0A494C067, A0A994J515, C9J8K5, C9JFT7, C9JI43, C9JZT0, E7EMG1, E7ERH1, E9PF55, E9PGF5, H0Y4U1, H7C3Z4

UniProt curated annotations — full annotation on UniProt →

Function. May act as a protein phosphatase and/or a lipid phosphatase. Involved in fibrillar adhesion formation. Essential for myofibroblast differentiation and myofibroblast-mediated extracellular matrix deposition. Enhances RHOA activation in the presence of DLC1. Plays a role in cell polarization and migration. May be involved in cartilage development and in linking signal transduction pathways to the cytoskeleton.

Subunit / interactions. Binds to actin filaments and interacts with phosphotyrosine-containing proteins. Interacts with STARD8. Interacts with protein phosphatase PPP1CA. Interacts (via N-terminus) with Rho GTPase-activating protein DLC1; the interaction is decreased by phosphorylation of TNS1. Interacts with tyrosine-phosphorylated proteins BCAR1/p130Cas and PTK2/FAK; the interactions are increased by phosphorylation of TNS1.

Subcellular location. Cell surface. Cell junction. Focal adhesion. Cytoplasm. Cytoskeleton.

Tissue specificity. In the lung, detected in the alveolar septa (at protein level). Ubiquitous.

Post-translational modifications. Extensively phosphorylated on serine and threonine residues in a p38 MAPK-dependent manner which reduces interaction with DLC1 and increases interaction with tyrosine-phosphorylated proteins including BCAR1/p130cas and PTK2/FAK. The majority of the phosphorylated Ser/Thr residues are immediately adjacent to a proline residue. Also phosphorylated on tyrosine residues. Rapidly cleaved by calpain II.

Induction. By transforming growth factor beta (TGFB) which is dependent on signaling through the transforming growth factor receptor TGFBR1 but is independent of SMAD signaling. ROCK activation, actin polymerization and MRTFA/MLK1 activation are required for TNS1 inducibility by TGFB.

Similarity. Belongs to the PTEN phosphatase protein family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9HBL0-3	1	yes
Q9HBL0-1	2
Q9HBL0-2	3

RefSeq proteins (4): NP_001294951, NP_001294952, NP_001374706, NP_072174 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR002219	PKC_DAG/PE	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR006020	PTB/PI_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR013625	PTB	Domain
IPR014020	Tensin_C2-dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR029023	Tensin_phosphatase	Domain
IPR033929	Tensin_PTB	Domain
IPR035012	Tensin-like_SH2	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR046349	C1-like_sf	Homologous_superfamily
IPR051484	Tensin_PTEN_phosphatase	Family

Pfam: PF00017, PF00130, PF08416, PF10409

UniProt features (81 total): modified residue 31, compositionally biased region 14, region of interest 9, sequence variant 7, splice variant 5, domain 4, mutagenesis site 4, sequence conflict 3, glycosylation site 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HBL0-F1	53.42	0.24

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 (31): 463, 489, 491, 503, 504, 558, 746, 826, 889, 894, 919, 985, 1024, 1028, 1032, 1088, 1092, 1228, 1281, 1293 …

Glycosylation sites (2): 1156, 1271

Mutagenesis-validated functional residues (4):

Position	Phenotype
369–370	reduces interaction with dlc1.
377–378	no effect on interaction with dlc1.
427	abolishes interaction with ppp1ca. reduces interaction with dlc1. increases phosphorylation of some ser/thr residues. re
1592	reduces interaction with dlc1 but does not affect interaction with ppp1ca. impaired cell polarization. reduced phosphory

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 304 (showing top): GOCC_CELL_SURFACE, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, MCBRYAN_TERMINAL_END_BUD_UP, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, CHANDRAN_METASTASIS_DN, CAGCTG_AP4_Q5, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, PAPASPYRIDONOS_UNSTABLE_ATEROSCLEROTIC_PLAQUE_DN, GOBP_CELL_JUNCTION_ORGANIZATION, GROSS_HYPOXIA_VIA_ELK3_UP, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_DN

GO Biological Process (2): cell-substrate junction assembly (GO:0007044), fibroblast migration (GO:0010761)

GO Molecular Function (7): RNA binding (GO:0003723), actin binding (GO:0003779), phosphoprotein phosphatase activity (GO:0004721), zinc ion binding (GO:0008270), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (6): cytoskeleton (GO:0005856), focal adhesion (GO:0005925), cell surface (GO:0009986), cytoplasm (GO:0005737), cell-substrate junction (GO:0030055), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell junction assembly	1
cell-substrate junction organization	1
ameboidal-type cell migration	1
nucleic acid binding	1
cytoskeletal protein binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
transition metal ion binding	1
binding	1
catalytic activity	1
cation binding	1
intracellular membraneless organelle	1
cell-substrate junction	1
intracellular anatomical structure	1
anchoring junction	1
cell junction	1

Protein interactions and networks

STRING

2133 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNS1	VCL	P18206	800
TNS1	SRC	P12931	770
TNS1	FN1	P02751	745
TNS1	TLN1	Q9Y490	688
TNS1	TLN2	Q9Y4G6	680
TNS1	PXN	P49023	661
TNS1	DLC1	Q96QB1	640
TNS1	AXL	P30530	618
TNS1	TGFB1I1	O43294	615
TNS1	BCAR1	P56945	609
TNS1	GSTCD	Q8NEC7	583
TNS1	PTK2	Q05397	577
TNS1	EGFR	P00533	535
TNS1	THSD4	Q6ZMP0	506
TNS1	ITGB3	P05106	489

IntAct

41 interactions, top by confidence:

A	B	Type	Score
DMD	DTNB	psi-mi:“MI:0914”(association)	0.890
TNS1	SORBS3	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
GPSM3	ATE1	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
TNS1	FLT3	psi-mi:“MI:0407”(direct interaction)	0.440
TNS1	CAPN2	psi-mi:“MI:0194”(cleavage reaction)	0.440
TNS1	AR	psi-mi:“MI:0407”(direct interaction)	0.440
TNS1	GAB1	psi-mi:“MI:0407”(direct interaction)	0.440
TNS1	KIT	psi-mi:“MI:0407”(direct interaction)	0.440
TNS1	MET	psi-mi:“MI:0407”(direct interaction)	0.440
TNS1	DLC1	psi-mi:“MI:0915”(physical association)	0.400
TNS1	LMNA	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
DLC1	TNS1	psi-mi:“MI:0915”(physical association)	0.370
TNS1	PCNA	psi-mi:“MI:0915”(physical association)	0.370
PPP1CC	TNS1	psi-mi:“MI:0915”(physical association)	0.370
TNS1	KLF10	psi-mi:“MI:0915”(physical association)	0.370
OSGEP	TNS1	psi-mi:“MI:0915”(physical association)	0.370
KCNC3	FYN	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ELL3	ARHGEF10	psi-mi:“MI:0914”(association)	0.350
FBXW11	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
FYN	MYCBP2	psi-mi:“MI:0914”(association)	0.350

BioGRID (42): TNS1 (Two-hybrid), BABAM1 (Affinity Capture-MS), BRCC3 (Affinity Capture-MS), CSK (Affinity Capture-MS), CTNNAL1 (Affinity Capture-MS), DMD (Affinity Capture-MS), DTNB (Affinity Capture-MS), FAM175B (Affinity Capture-MS), SNTB1 (Affinity Capture-MS), SNTB2 (Affinity Capture-MS), SORBS3 (Affinity Capture-MS), UTRN (Affinity Capture-MS), TNS1 (Affinity Capture-MS), TNS1 (Affinity Capture-Western), TNS1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0G2JUG7, A1L390, E9Q0S6, O08774, O14924, O15085, O43182, O54834, O54960, O60307, O75052, P57095, Q13009, Q3U1V8, Q3U214, Q3UHC7, Q4VAC9, Q5DU25, Q5JU85, Q5RBI7, Q5SXA9, Q5VWQ8, Q60610, Q64512, Q6AX33, Q6DN90, Q6NXJ0, Q6P0Q8, Q6P1I6, Q6ZMN7, Q76G19, Q76LL6, Q76M68, Q7T2V3, Q810W7, Q8CGE9, Q8IX03, Q8R0S2, Q8R4H2, Q8WYP3

Diamond homologs: E9Q0S6, G5EE01, H2L045, O08586, O14976, O54857, P60483, P60484, P97874, Q04205, Q32PJ7, Q4R6N0, Q4V8I3, Q54JL7, Q5SSZ5, Q63HR2, Q68CZ2, Q6NR09, Q8BZ33, Q8CGB6, Q8H106, Q8IZW8, Q8T9S7, Q99KY4, Q9FLZ5, Q9GLM4, Q9HBL0, Q9LT75, Q9PUT6, O94526, P56180, Q9P7H1, G5ECJ6, Q5B323, Q6XPS3, Q86IL4, A0AUV4, A8WYE4, B0WAU8, D2I3C6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Constitutive Signaling by Aberrant PI3K in Cancer	6	20.0×	2e-04
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	6	15.3×	5e-04
PIP3 activates AKT signaling	6	10.5×	3e-03
RAF/MAP kinase cascade	6	9.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	286
Likely benign	40
Benign	47

Top pathogenic / likely-pathogenic (0)

SpliceAI

6038 predictions. Top by Δscore:

Variant	Effect	Δscore
2:217808073:A:AC	donor_gain	1.0000
2:217808074:C:CC	donor_gain	1.0000
2:217808596:GACTT:G	donor_loss	1.0000
2:217808597:ACTTA:A	donor_loss	1.0000
2:217808599:TTAC:T	donor_loss	1.0000
2:217808600:TACT:T	donor_loss	1.0000
2:217808601:A:AC	donor_gain	1.0000
2:217808601:ACTTT:A	donor_gain	1.0000
2:217808602:C:CT	donor_gain	1.0000
2:217808602:CT:C	donor_gain	1.0000
2:217808602:CTT:C	donor_gain	1.0000
2:217808602:CTTT:C	donor_gain	1.0000
2:217808602:CTTTC:C	donor_gain	1.0000
2:217808605:T:A	donor_gain	1.0000
2:217808609:T:A	donor_gain	1.0000
2:217808667:AGAGC:A	acceptor_gain	1.0000
2:217808669:AGC:A	acceptor_gain	1.0000
2:217809818:CTTAC:C	donor_loss	1.0000
2:217809819:TTACT:T	donor_loss	1.0000
2:217809821:A:AC	donor_gain	1.0000
2:217809821:AC:A	donor_loss	1.0000
2:217809822:C:CT	donor_gain	1.0000
2:217809822:CT:C	donor_gain	1.0000
2:217809822:CTT:C	donor_gain	1.0000
2:217809822:CTTT:C	donor_gain	1.0000
2:217809825:T:A	donor_gain	1.0000
2:217809988:CAGG:C	acceptor_gain	1.0000
2:217809992:C:CC	acceptor_gain	1.0000
2:217810243:CTCA:C	donor_loss	1.0000
2:217810244:TCACC:T	donor_loss	1.0000

AlphaMissense

11993 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:217809874:A:T	V1637D	1.000
2:217813236:A:G	C1541R	1.000
2:217813239:C:G	G1540R	1.000
2:217813244:A:G	L1538P	1.000
2:217813244:A:T	L1538H	1.000
2:217813250:A:T	V1536D	1.000
2:217813271:A:T	I1529K	1.000
2:217813274:A:G	L1528P	1.000
2:217813276:A:C	F1527L	1.000
2:217813276:A:T	F1527L	1.000
2:217813277:A:G	F1527S	1.000
2:217813278:A:G	F1527L	1.000
2:217813286:A:T	V1524D	1.000
2:217813735:G:T	A1500D	1.000
2:217813738:A:G	L1499P	1.000
2:217813741:C:T	G1498E	1.000
2:217813742:C:A	G1498W	1.000
2:217813742:C:G	G1498R	1.000
2:217813742:C:T	G1498R	1.000
2:217813764:A:C	S1490R	1.000
2:217813764:A:T	S1490R	1.000
2:217813766:T:G	S1490R	1.000
2:217813771:C:G	R1488P	1.000
2:217813772:G:T	R1488S	1.000
2:217813774:A:T	I1487N	1.000
2:217813804:A:G	L1477P	1.000
2:217885163:A:G	L248P	1.000
2:217885755:C:G	G244R	1.000
2:217885755:C:T	G244R	1.000
2:217886581:A:G	L186P	1.000

dbSNP variants (sampled 300 via entrez): RS1000012011 (2:217951666 A>C,G), RS1000020562 (2:217993768 A>G), RS1000048965 (2:217967575 A>G), RS1000061527 (2:217950764 T>G), RS1000069290 (2:217911105 C>T), RS1000096409 (2:217926155 A>G), RS1000107130 (2:218022817 G>A,T), RS1000111518 (2:217813525 A>G), RS1000136582 (2:218031413 A>C,G,T), RS1000139702 (2:217993567 G>A), RS1000143293 (2:217880019 T>A), RS1000148085 (2:217910761 C>CA,CAA), RS1000149056 (2:217850927 C>T), RS1000151220 (2:217842180 C>A), RS1000172694 (2:217931589 G>A)

Disease associations

OMIM: gene MIM:600076 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

55 associations (top):

Study	Trait	p-value
GCST000544_3	Pulmonary function	1.000000e-12
GCST000817_182	Height	2.000000e-14
GCST001263_21	Height	2.000000e-06
GCST001784_44	Pulmonary function (smoking interaction)	8.000000e-09
GCST002322_17	Asthma and hay fever	6.000000e-07
GCST002647_81	Height	1.000000e-17
GCST002702_94	Height	9.000000e-06
GCST003094_2	Mitral valve prolapse	3.000000e-11
GCST004183_28	Lung function (FEV1)	2.000000e-10
GCST004184_18	Lung function (FVC)	1.000000e-06
GCST004185_53	Lung function (FEV1/FVC)	5.000000e-08
GCST004280_90	Diastolic blood pressure	1.000000e-12
GCST004611_19	High light scatter reticulocyte count	2.000000e-18
GCST004612_54	High light scatter reticulocyte percentage of red cells	1.000000e-17
GCST004628_152	Immature fraction of reticulocytes	5.000000e-30
GCST005170_6	Intraocular pressure	7.000000e-12
GCST005194_94	Coronary artery disease	2.000000e-08
GCST005194_95	Coronary artery disease	3.000000e-08
GCST005195_30	Coronary artery disease	2.000000e-12
GCST005196_215	Coronary artery disease	1.000000e-12
GCST005580_231	Intraocular pressure	2.000000e-17
GCST005580_232	Intraocular pressure	2.000000e-17
GCST006394_50	Intraocular pressure	4.000000e-09
GCST006412_5	Intraocular pressure	1.000000e-09
GCST006479_62	Diverticular disease	4.000000e-07
GCST007094_174	Diastolic blood pressure	1.000000e-12
GCST007098_65	Diastolic blood pressure	5.000000e-06
GCST007098_66	Diastolic blood pressure	5.000000e-06
GCST007099_130	Systolic blood pressure	2.000000e-10
GCST007267_296	Systolic blood pressure	1.000000e-09

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004314	forced expiratory volume
EFO:0004312	vital capacity
EFO:0004713	FEV/FVC ratio
EFO:0006336	diastolic blood pressure
EFO:0007986	reticulocyte count
EFO:0004695	intraocular pressure measurement
EFO:0009959	diverticular disease
EFO:0006335	systolic blood pressure
EFO:0007710	cognitive decline measurement
EFO:0007874	gut microbiome measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, affects methylation, decreases expression, increases expression, increases methylation	5
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	5
bisphenol A	affects expression, decreases expression, increases expression	4
(+)-JQ1 compound	decreases expression	3
Estradiol	affects cotreatment, increases expression, decreases expression	3
Aflatoxin B1	increases expression, increases methylation	3
Acetaminophen	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	increases expression	1
sodium bichromate	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
nickel chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	affects methylation	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
ciglitazone	affects binding, increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
Am 580	decreases expression	1
CGP 52608	affects binding, increases reaction	1
3-nitrobenzanthrone	affects expression	1

Clinical trials (associated diseases)

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