TRIP6

Summary

TRIP6 (thyroid hormone receptor interactor 6, HGNC:12311) is a protein-coding gene on chromosome 7q22.1, encoding Thyroid receptor-interacting protein 6 (Q15654). Relays signals from the cell surface to the nucleus to weaken adherens junction and promote actin cytoskeleton reorganization and cell invasiveness.

This gene is a member of the zyxin family and encodes a protein with three LIM zinc-binding domains. This protein localizes to focal adhesion sites and along actin stress fibers. Recruitment of this protein to the plasma membrane occurs in a lysophosphatidic acid (LPA)-dependent manner and it regulates LPA-induced cell migration. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized.

Source: NCBI Gene 7205 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 86 total
• MANE Select transcript: NM_003302

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12311
Approved symbol	TRIP6
Name	thyroid hormone receptor interactor 6
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	ZRP-1, OIP1, MGC10556, MGC10558, MGC29959, MGC3837, MGC4423
Ensembl gene	ENSG00000087077
Ensembl biotype	protein_coding
OMIM	602933
Entrez	7205

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 15 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000200457, ENST00000417475, ENST00000429658, ENST00000437505, ENST00000463125, ENST00000476870, ENST00000488670, ENST00000496260, ENST00000619988, ENST00000893591, ENST00000893592, ENST00000893593, ENST00000893594, ENST00000893595, ENST00000893596, ENST00000893597, ENST00000893598, ENST00000893599, ENST00000936779, ENST00000936780, ENST00000966331

RefSeq mRNA: 1 — MANE Select: NM_003302 NM_003302

CCDS: CCDS5708

Canonical transcript exons

ENST00000200457 — 9 exons

Exon	Start	End
ENSE00000710158	100867861	100867988
ENSE00001833240	100873172	100873454
ENSE00003542941	100868108	100868233
ENSE00003627350	100867387	100867606
ENSE00003653515	100871543	100871721
ENSE00003663967	100870574	100870743
ENSE00003668833	100868495	100868866
ENSE00003677297	100872624	100872744
ENSE00003679725	100870370	100870463

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.3244 / max 101.5025, expressed in 1701 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80060	23.3244	1701

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	98.10	gold quality
body of uterus	UBERON:0009853	97.77	gold quality
metanephros cortex	UBERON:0010533	97.60	gold quality
right lobe of thyroid gland	UBERON:0001119	97.48	gold quality
palpebral conjunctiva	UBERON:0001812	97.43	gold quality
endocervix	UBERON:0000458	97.37	gold quality
left uterine tube	UBERON:0001303	97.34	gold quality
nipple	UBERON:0002030	97.29	gold quality
left lobe of thyroid gland	UBERON:0001120	97.24	gold quality
ectocervix	UBERON:0012249	97.24	gold quality
ascending aorta	UBERON:0001496	97.21	gold quality
thoracic aorta	UBERON:0001515	97.20	gold quality
mucosa of stomach	UBERON:0001199	97.14	gold quality
descending thoracic aorta	UBERON:0002345	97.11	gold quality
right coronary artery	UBERON:0001625	97.02	gold quality
aorta	UBERON:0000947	96.97	gold quality
right uterine tube	UBERON:0001302	96.92	gold quality
popliteal artery	UBERON:0002250	96.84	gold quality
tibial artery	UBERON:0007610	96.84	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.81	gold quality
right adrenal gland cortex	UBERON:0035827	96.72	gold quality
right ovary	UBERON:0002118	96.70	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.68	gold quality
lower esophagus	UBERON:0013473	96.67	gold quality
left ovary	UBERON:0002119	96.65	gold quality
thyroid gland	UBERON:0002046	96.63	gold quality
esophagus mucosa	UBERON:0002469	96.58	gold quality
tibial nerve	UBERON:0001323	96.50	gold quality
esophagus	UBERON:0001043	96.47	gold quality
skin of leg	UBERON:0001511	96.44	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	59.58
E-ANND-3	yes	11.60

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CDK6	Unknown

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

15 targeting TRIP6, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-3691-5P	98.62	65.88	552
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-1270	96.94	66.65	931
HSA-MIR-620	96.94	66.79	888
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-1245A	96.33	66.25	498
HSA-MIR-8079	96.33	66.11	484
HSA-MIR-4471	95.11	66.84	755

Literature-anchored findings (GeneRIF, showing 32)

• the OIP-1 c-peptide is the functional domain of OIP-1 (PMID:11771657)
• TRIP6 functions at a point of convergence between the activated LPA(2) receptor and downstream signals involved in cell adhesion and migration (PMID:14688263)
• Analysis of the subcellular distribution of ZRP-1 demonstrated that in the absence of endoglin, ZRP-1 mainly localizes to focal adhesion sites, whereas in the presence of endoglin ZRP-1 is found along actin stress fibers. (PMID:15148318)
• ZRP-1 has a role in endoglin regulation of cytoskeletal organization (PMID:15148318)
• The data establish a physical and functional association between TRIP6 and RIP2, and suggest that RIP2’s involvement in multiple NF-kappaB and ERK activation pathways is mediated through TRIP6. (PMID:15657077)
• Binding of LPP and TRIP6 to Scrib links Scrib to a communication pathway between cell-cell contacts and the nucleus, and implicates these zyxin family members in Scrib-associated functions. (PMID:16137684)
• The TRIP6 knock-down led to an increased number of longer stress fibers and to the induction of locomotive phenotype in carcinoma cells. (PMID:16240724)
• AMPK phosphorylated TRIP6 in vitro at the N-terminus and the transcriptional co-activator properties of TRIP6 were enhanced by AMPK action. (PMID:16624523)
• ZRP-1 plays a crucial role in coupling the cell-matrix/cell-cell-contact signals with Rho GTPase-mediated actin remodeling by localizing at cell-matrix and cell-cell contact sites. (PMID:17652164)
• OIP-1 inhibits measles virus nucleocapsid protein induced pagetic osteoclast formation/activity through suppression of RANK signaling (PMID:18348201)
• TRIP6 overexpression in colon tumors suggests its critical role in cancer progression. (PMID:19017743)
• IL-12 stimulates the OIP-1 gene expression through STAT-3 activation in CD4+ T cells. (PMID:19259951)
• TRIP6 promotes Fas-mediated cell migration in apoptosis-resistant glioma cells. This effect is regulated via the Src-dependent phosphorylation of TRIP6 at Tyr-55. (PMID:20876301)
• TRIP6 is an adaptor protein that regulates cell motility, antiapoptotic signaling and transcriptional activity. (Review) (PMID:21689746)
• TRIP6 is a nucleocytoplasmatic shuttle protein essential for the coordination of focal adhesion dynamics and transcriptional responses in lysophosphosphatidic (LPA) and NF-kappaB signaling. (PMID:22054418)
• TRIP6 is engaged in cell proliferation, differentiation, transcription regulation and contributes to genome stability. [Review] (PMID:22054418)
• High TRIP6 expression is associated with malignant pleural mesothelioma. (PMID:23313295)
• TRIP6 also promotes serum-induced reduction of nuclear p27(KIP1) expression levels. (PMID:23339869)
• TRIP6 is involved in the regulation of nasopharyngeal carcinoma cell motility, and phosphorylation of tyrosine 55 residue plays an important regulatory role for this event (PMID:23576104)
• TRIP6 acts, in contrast to Zyxin, as an oncogene that partially accounts for the autonomous migratory, invasive and proliferative properties of Ewing’s sarcoma cells. (PMID:24033704)
• TRIP6 overexpression promotes migration, invasion, and clonogenicity of Ewing’s sarcoma cells (PMID:24033704)
• the Trip6-GRIP1-myosin VI interaction and its regulation on F-actin network play a significant role in dendritic morphogenesis (PMID:25673849)
• TRIP6 promotes tumor proliferation and reverses cell adhesion-mediated drug resistance via regulating nuclear p27(Kip1) expression in non-Hodgkin’s lymphoma (PMID:26298725)
• Taken together, these findings showed that TRIP6 plays an important role in promoting HCC cells proliferation and may serve as a novel prognostic biomarker and therapeutic target in HCC. (PMID:29080747)
• TRIP6 acts as an intermediary connecting tension monitoring at adherens junctions to Hippo signaling, which has implications for how tension contributes to growth of organs and tissues during development, tissue repair during injury and to pathological conditions such as cancer. (PMID:29222344)
• MiR-7 directly inhibited TRIP6 expression in colorectal cancer.TRIP6 is involved in important colorectal cancer cellular processes, including cell migration, invasion, proliferation, differentiation and survival.Colorectal cancer patients with higher expression of TRIP6 had poor a poorer prognosis. (PMID:31029422)
• High TRIP6 expression is associated with Cell Proliferation, Cell Migration and Invasion in Endometrial Carcinoma. (PMID:31424277)
• TRIP6 promotes tumorigenic capability through regulating FOXC1 in hepatocellular carcinoma. (PMID:32046874)
• TRIP6 accelerates the proliferation and invasion of cervical cancer by upregulating oncogenic YAP signaling. (PMID:32853630)
• The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes. (PMID:35008510)
• ABCB1 Amplicon Contains Cyclic AMP Response Element-Driven TRIP6 Gene in Taxane-Resistant MCF-7 Breast Cancer Sublines. (PMID:36833223)
• TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association. (PMID:38369589)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	trip6	ENSDARG00000069331
mus_musculus	Trip6	ENSMUSG00000023348
rattus_norvegicus	Trip6	ENSRNOG00000048580
caenorhabditis_elegans		WBGENE00006839

Paralogs (1): ZYX (ENSG00000159840)

Protein

Protein identifiers

Thyroid receptor-interacting protein 6 — Q15654 (reviewed: Q15654)

Alternative names: Opa-interacting protein 1, Zyxin-related protein 1

All UniProt accessions (3): Q15654, F2ZC06, H7BZE2

UniProt curated annotations — full annotation on UniProt →

Function. Relays signals from the cell surface to the nucleus to weaken adherens junction and promote actin cytoskeleton reorganization and cell invasiveness. Involved in lysophosphatidic acid-induced cell adhesion and migration. Acts as a transcriptional coactivator for NF-kappa-B and JUN, and mediates the transrepression of these transcription factors induced by glucocorticoid receptor.

Subunit / interactions. Specifically interacts with the ligand binding domain of the thyroid receptor (TR) in the presence of thyroid hormone. Interacts (via the third LIM domain and C-terminus) with PTPN13 (via the second PDZ domain). Interacts (via the second LIM domain or via the third LIM domain plus C-terminus) with PDLIM4 (via PDZ domain). Found in a complex with PTPN13 and PDLIM4. Interacts with SVIL isoform 2. Interacts with LPAR2 but not other LPA receptors. Interacts with PRKAA2. Interacts with MAGI1. Interacts with SCRIB. In case of infection, interacts with S.typhimurium protein sseI.

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

Tissue specificity. Abundantly expressed in kidney, liver and lung. Lower levels in heart, placenta and pancreas. Expressed in colonic epithelial cells. Up-regulated in colonic tumors.

Post-translational modifications. Phosphorylation at Tyr-55 by SRC is required for enhancement of lysophosphatidic acid-induced cell migration. Tyr-55 is dephosphorylated by PTPN13.

Domain organisation. The LIM zinc-binding domains mediate interaction with LPAR2 and with S.typhimurium protein sseI.

Similarity. Belongs to the zyxin/ajuba family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q15654-1	1	yes
Q15654-2	2
Q15654-3	3

RefSeq proteins (1): NP_003293* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain

Pfam: PF00412

UniProt features (51 total): modified residue 13, strand 9, sequence conflict 5, splice variant 4, domain 3, sequence variant 3, mutagenesis site 3, region of interest 3, turn 3, helix 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1X61	SOLUTION NMR
2DLO	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15654-F1	63.78	0.20

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 (13): 25, 55, 92, 111, 142, 179, 186, 189, 205, 236, 238, 249, 25

Mutagenesis-validated functional residues (3):

Position	Phenotype
101	exclusively located in nucleus.
102	exclusively located in nucleus.
474	reduces interaction with magi1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 216 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, CHIBA_RESPONSE_TO_TSA_UP, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_FOCAL_ADHESION_ASSEMBLY, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_CELL_JUNCTION_ORGANIZATION, UEDA_PERIFERAL_CLOCK, GOBP_POSITIVE_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (6): signal transduction (GO:0007165), positive regulation of cell migration (GO:0030335), chordate embryonic development (GO:0043009), focal adhesion assembly (GO:0048041), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), cell adhesion (GO:0007155)

GO Molecular Function (6): RNA binding (GO:0003723), interleukin-1 receptor binding (GO:0005149), kinase binding (GO:0019900), metal ion binding (GO:0046872), nuclear thyroid hormone receptor binding (GO:0046966), protein binding (GO:0005515)

GO Cellular Component (8): stress fiber (GO:0001725), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), focal adhesion (GO:0005925), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
cellular anatomical structure	2
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
embryo development ending in birth or egg hatching	1
cell-substrate junction assembly	1
cell-matrix adhesion	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
nucleic acid binding	1
cytokine receptor binding	1
growth factor receptor binding	1
enzyme binding	1
cation binding	1
nuclear receptor binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
cell-substrate junction	1
cell junction	1

Protein interactions and networks

STRING

1276 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIP6	OIP5	O43482	853
TRIP6	BCAR1	P56945	807
TRIP6	EXOSC8	Q96B26	795
TRIP6	NHERF2	Q15599	785
TRIP6	PRAME	P78395	774
TRIP6	PKM	P14618	773
TRIP6	VCL	P18206	762
TRIP6	LPAR2	Q9HBW0	747
TRIP6	SHARPIN	Q9H0F6	696
TRIP6	TXNRD2	Q9NNW7	676
TRIP6	ENG	P17813	610
TRIP6	PTPN13	Q12923	565
TRIP6	RHOG	P35238	560
TRIP6	NEDD9	Q14511	558
TRIP6	GIPC1	O14908	546

IntAct

774 interactions, top by confidence:

A	B	Type	Score
NCK2	TRIP6	psi-mi:“MI:0915”(physical association)	0.830
TRIP6	NCK2	psi-mi:“MI:0915”(physical association)	0.830
TRIP6	AQP1	psi-mi:“MI:0915”(physical association)	0.780
CATSPER1	TRIP6	psi-mi:“MI:0915”(physical association)	0.780
AQP1	TRIP6	psi-mi:“MI:0915”(physical association)	0.780
TRIP6	METTL17	psi-mi:“MI:0915”(physical association)	0.740
TRIP6	FRS3	psi-mi:“MI:0915”(physical association)	0.720
FRS3	TRIP6	psi-mi:“MI:0915”(physical association)	0.720
OIP5	TRIP6	psi-mi:“MI:0915”(physical association)	0.670
CTAG2	TRIP6	psi-mi:“MI:0915”(physical association)	0.670
BYSL	TRIP6	psi-mi:“MI:0915”(physical association)	0.670
TRIP6	GSE1	psi-mi:“MI:0915”(physical association)	0.670
EXOC3-AS1	TRIP6	psi-mi:“MI:0915”(physical association)	0.670
TRIP6	TEKT4	psi-mi:“MI:0915”(physical association)	0.670
TRIP6	ABI2	psi-mi:“MI:0915”(physical association)	0.670
TRIP6	CTAG2	psi-mi:“MI:0915”(physical association)	0.670
TEKT4	TRIP6	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (489): TRIP6 (Two-hybrid), TRIP6 (Two-hybrid), TRIP6 (Two-hybrid), TRIP6 (Two-hybrid), TRIP6 (Two-hybrid), TRIP6 (Two-hybrid), TRIP6 (Two-hybrid), TRIP6 (Two-hybrid), TRIP6 (Two-hybrid), TRIP6 (Two-hybrid), TRIP6 (Two-hybrid), TRIP6 (Two-hybrid), TRIP6 (Two-hybrid), TRIP6 (Two-hybrid), TRIP6 (Two-hybrid)

ESM2 similar proteins: A0A0U1RQ45, A0A1B0GWB2, A2A9T0, A6QPA0, A7MCY6, D3ZFB6, E9PUL5, E9Q0B3, F5GYI3, F5H4A9, J3QNX5, O70142, P0C1G7, P81408, P97764, P98077, Q148V8, Q15654, Q2KI80, Q3SX26, Q3SZL6, Q4V9L6, Q5FVJ4, Q5FW56, Q5RAC1, Q5T7N3, Q6DG50, Q6PAJ3, Q6PJ61, Q6ZMQ8, Q6ZNR0, Q6ZRV2, Q75VX8, Q7Z6L0, Q86UK7, Q86VE0, Q8BGW2, Q8BRJ3, Q8BX43, Q8C0R7

Diamond homologs: A0JNI8, A0M8S5, A1ZA47, A2PZF9, A5H447, A6NIX2, A8DZE6, A9LS46, B5DEH0, B7ZUL2, E1BKA3, G5E5X0, G5EEA1, O43294, O60663, O88609, P35688, P37137, P48742, P53411, P53413, P61375, P61376, P61968, P61969, P63006, P63007, P63008, Q04584, Q06BR1, Q07E40, Q0VA45, Q15654, Q15942, Q1JQB5, Q2IBC3, Q3MHZ4, Q3SWZ8, Q3SX26, Q3SX40

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TRIP6	“up-regulates activity”	TRAF6	binding
PTPN13	“down-regulates activity”	TRIP6	dephosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1159 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100870453:G:GT	donor_gain	1.0000
7:100870453:G:T	donor_gain	1.0000
7:100870671:ATGCC:A	acceptor_gain	1.0000
7:100870672:T:G	acceptor_gain	1.0000
7:100871538:A:AG	acceptor_gain	1.0000
7:100871540:CAGGC:C	acceptor_loss	1.0000
7:100871541:A:AG	acceptor_gain	1.0000
7:100871541:A:T	acceptor_loss	1.0000
7:100871541:AG:A	acceptor_gain	1.0000
7:100871542:G:GA	acceptor_gain	1.0000
7:100871542:GG:G	acceptor_gain	1.0000
7:100871542:GGC:G	acceptor_gain	1.0000
7:100871542:GGCC:G	acceptor_gain	1.0000
7:100871542:GGCCA:G	acceptor_gain	1.0000
7:100871711:G:GT	donor_gain	1.0000
7:100871717:CACAG:C	donor_loss	1.0000
7:100871718:ACAG:A	donor_loss	1.0000
7:100871719:CAGGT:C	donor_loss	1.0000
7:100871722:GTC:G	donor_loss	1.0000
7:100872738:G:GG	donor_gain	1.0000
7:100868093:T:TA	acceptor_gain	0.9900
7:100868094:G:A	acceptor_gain	0.9900
7:100868640:TGC:T	donor_gain	0.9900
7:100870464:G:GG	donor_gain	0.9900
7:100870464:GTGAG:G	donor_loss	0.9900
7:100870465:T:A	donor_loss	0.9900
7:100870573:GGCCA:G	acceptor_gain	0.9900
7:100870663:T:G	acceptor_gain	0.9900
7:100870669:A:AG	acceptor_gain	0.9900
7:100870675:C:A	acceptor_gain	0.9900

AlphaMissense

3044 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100871630:T:C	F363L	1.000
7:100871631:T:C	F363S	1.000
7:100871631:T:G	F363C	1.000
7:100871632:C:A	F363L	1.000
7:100871632:C:G	F363L	1.000
7:100871636:T:C	C365R	1.000
7:100871637:G:A	C365Y	1.000
7:100871637:G:T	C365F	1.000
7:100871638:C:G	C365W	1.000
7:100871672:T:C	F377L	1.000
7:100871673:T:C	F377S	1.000
7:100871674:C:A	F377L	1.000
7:100871674:C:G	F377L	1.000
7:100871699:C:G	H386D	1.000
7:100871702:T:A	C387S	1.000
7:100871702:T:C	C387R	1.000
7:100871703:G:A	C387Y	1.000
7:100871703:G:C	C387S	1.000
7:100871704:C:G	C387W	1.000
7:100871714:T:C	F391L	1.000
7:100871715:T:C	F391S	1.000
7:100871715:T:G	F391C	1.000
7:100871716:T:A	F391L	1.000
7:100871716:T:G	F391L	1.000
7:100872628:T:C	F395L	1.000
7:100872630:T:A	F395L	1.000
7:100872630:T:G	F395L	1.000
7:100872640:T:A	C399S	1.000
7:100872640:T:C	C399R	1.000
7:100872641:G:A	C399Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000228673 (7:100868969 A>G), RS1000444268 (7:100869188 C>T), RS1000627721 (7:100865441 G>A), RS1000705298 (7:100867323 G>A,C), RS1000723995 (7:100867032 G>T), RS1001330916 (7:100865948 T>C,G), RS1001372769 (7:100870315 T>C), RS1002240139 (7:100871353 T>C), RS1002637443 (7:100867786 A>C,T), RS1002832937 (7:100869280 G>A), RS1002933197 (7:100873013 G>A), RS1003185849 (7:100872986 G>T), RS1003638199 (7:100868361 A>G), RS1004257687 (7:100873754 G>A), RS1004878380 (7:100873368 C>G)

Disease associations

OMIM: gene MIM:602933 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001684_4	Plasminogen activator inhibitor type 1 levels (PAI-1)	6.000000e-13
GCST005845_4	Heart rate increase in response to exercise	3.000000e-16
GCST005846_7	Heart rate response to recovery post exercise (10 sec)	6.000000e-21
GCST005847_9	Heart rate response to recovery post exercise (20 sec)	3.000000e-21
GCST005848_15	Heart rate response to recovery post exercise (50 sec)	4.000000e-23
GCST005849_14	Heart rate response to recovery post exercise (40 sec)	6.000000e-24
GCST005850_6	Heart rate response to recovery post exercise (30 sec)	8.000000e-23
GCST007250_7	Nonunion in individuals with fractures	3.000000e-07
GCST008103_164	Bipolar disorder	7.000000e-06
GCST90011900_190	Serum alkaline phosphatase levels	1.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004792	plasminogen activator inhibitor 1 measurement
EFO:0009184	heart rate response to exercise
EFO:0009185	heart rate response to recovery post exercise
EFO:0009707	fractures, ununited
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, decreases methylation, increases expression	3
Valproic Acid	increases methylation, affects cotreatment, increases expression, affects expression, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
cobaltous chloride	increases expression	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
chloropicrin	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
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
MRK 003	decreases expression	1
Troglitazone	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Diethylstilbestrol	decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

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