TES

Summary

TES (testin LIM domain protein, HGNC:14620) is a protein-coding gene on chromosome 7q31.2, encoding Testin (Q9UGI8). Scaffold protein that may play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton.

Cancer-associated chromosomal changes often involve regions containing fragile sites. This gene maps to a common fragile site on chromosome 7q31.2 designated FRA7G. This gene is similar to mouse Testin, a testosterone-responsive gene encoding a Sertoli cell secretory protein containing three LIM domains. LIM domains are double zinc-finger motifs that mediate protein-protein interactions between transcription factors, cytoskeletal proteins and signaling proteins. This protein is a negative regulator of cell growth and may act as a tumor suppressor. This scaffold protein may also play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton. Multiple protein isoforms are encoded by transcript variants of this gene.

Source: NCBI Gene 26136 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 50 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_015641

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14620
Approved symbol	TES
Name	testin LIM domain protein
Location	7q31.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP586B2022, TESS-2, TESTIN
Ensembl gene	ENSG00000135269
Ensembl biotype	protein_coding
OMIM	606085
Entrez	26136

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 15 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000358204, ENST00000393481, ENST00000393484, ENST00000455989, ENST00000461440, ENST00000463746, ENST00000485009, ENST00000492891, ENST00000494384, ENST00000496871, ENST00000496912, ENST00000898315, ENST00000898316, ENST00000898317, ENST00000898318, ENST00000898319, ENST00000937597, ENST00000937598, ENST00000937599, ENST00000952265, ENST00000952266, ENST00000952267

RefSeq mRNA: 2 — MANE Select: NM_015641 NM_015641, NM_152829

CCDS: CCDS5763, CCDS5764

Canonical transcript exons

ENST00000358204 — 7 exons

Exon	Start	End
ENSE00000919364	116250161	116250496
ENSE00001864576	116257294	116258783
ENSE00001915255	116210539	116210734
ENSE00003497314	116249020	116249272
ENSE00003521514	116251760	116251975
ENSE00003524843	116252318	116252476
ENSE00003760171	116234534	116234619

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 99.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.6740 / max 2274.5702, expressed in 1780 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80589	41.3563	1770
80590	3.0403	1212
80591	2.0654	945
80606	0.9439	570
80604	0.4858	272
80605	0.2363	104
80593	0.1543	34
80595	0.1291	22
80601	0.0903	19
80599	0.0756	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	99.22	gold quality
seminal vesicle	UBERON:0000998	99.09	gold quality
saphenous vein	UBERON:0007318	99.05	gold quality
blood vessel layer	UBERON:0004797	99.04	gold quality
mucosa of stomach	UBERON:0001199	98.56	gold quality
superficial temporal artery	UBERON:0001614	98.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.01	gold quality
sigmoid colon	UBERON:0001159	97.80	gold quality
descending thoracic aorta	UBERON:0002345	97.52	gold quality
nipple	UBERON:0002030	97.34	gold quality
myometrium	UBERON:0001296	97.32	gold quality
smooth muscle tissue	UBERON:0001135	97.28	gold quality
thoracic aorta	UBERON:0001515	97.21	gold quality
aorta	UBERON:0000947	97.18	gold quality
popliteal artery	UBERON:0002250	97.15	gold quality
tibial artery	UBERON:0007610	97.14	gold quality
ascending aorta	UBERON:0001496	97.13	gold quality
amniotic fluid	UBERON:0000173	96.97	gold quality
colonic mucosa	UBERON:0000317	96.94	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.93	gold quality
urinary bladder	UBERON:0001255	96.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.87	gold quality
urethra	UBERON:0000057	96.86	gold quality
lower esophagus	UBERON:0013473	96.84	gold quality
palpebral conjunctiva	UBERON:0001812	96.78	gold quality
mammary duct	UBERON:0001765	96.69	gold quality
rectum	UBERON:0001052	96.55	gold quality
vermiform appendix	UBERON:0001154	96.54	gold quality
large intestine	UBERON:0000059	96.50	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	323.35
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR5A1

miRNA regulators (miRDB)

114 targeting TES, 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-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833

Literature-anchored findings (GeneRIF, showing 33)

• TES is best candidate tumor suppressor gene at 7q31 in prostate tumors (PMID:15252854)
• Loss of TES from focal adhesions results in loss of actin stress fibres. (PMID:15662727)
• Oservations identify Tes as an atypical binding partner of EVH1 domain of Mena and a regulator specific to a single Ena/VASP family member. (PMID:18158903)
• Results suggest that testin has different conformational states in different cellular compartments, and a “closed” conformational state of TES may be involved in nucleolar localization. (PMID:18696217)
• The expression level of TES is significantly down-regulated in primary gastric cancer. (PMID:18799041)
• Inactivation of TESTIN is involved in head and neck carcinogenesis through its downregulation. (PMID:19289703)
• TES gene functions as a tumor suppressor gene and is frequently silenced by hypermethylation and loss of heterozygosity in ovarian cancers. (PMID:20180808)
• data implicate TES methylation in ALL and provide additional evidence for the involvement of LIM domain proteins in leukaemogenesis (PMID:20573277)
• results support the role of TES as a TSG in gastric carcinogenesis and that TES is inactivated primarily by LOH and CpG island methylation (PMID:20626849)
• Molecular recognition of the Tes LIM2-3 domains by the actin-related protein Arp7A. (PMID:21278383)
• These results suggest an interplay between the CaR and testin in the regulation of CaR-mediated Rho signalling with possible effects on the cytoskeleton. (PMID:21843504)
• Low TES gene expression is associated with coronary artery disease. (PMID:22156939)
• Alterations of TES mRNA level may predict the location of metastasis. CAV1 possibly affect the cancer cell invasion (PMID:22201996)
• TES, as a valuable marker of breast cancer prognosis, plays an important role in the development and progression of breast cancer. TES may be an effective novel target in breast cancer prevention and treatment. (PMID:22957844)
• A further significant correlation was observed between TES downregulation and the luminal B subtype independent of survivin expression. (PMID:23715752)
• TESTIN was commonly downregulated in human endometrial carcinoma and was associated with poor prognostic markers. (PMID:24929083)
• Downregulation of TES was associated with breast cancer. (PMID:25119600)
• findings suggest that the TES gene is a novel tumor suppressor gene (PMID:25498217)
• TESTIN was hypermethylated in 43.7% endometrial cancer tissues (p < 0.001). Moreover, TESTIN hypermethylation was significantly correlated with advanced tumor stage, deep myometrial invasion and lymphatic node metastasis. (PMID:25720371)
• Loss of TES gene expression is associated with nasopharyngeal carcinoma. (PMID:25824796)
• VASP, zyxin and TES are tension-dependent members of focal adherens junctions independent of the alpha-catenin-vinculin module. (PMID:26611125)
• we confirm that the TES promoter is unmethylated in normal adult and fetal tissues. Re-expression of TESTIN protein in acute lymphoblastic leukemia cells using expression plasmid transfection results in rapid cell death or cell cycle arrest. (PMID:26985820)
• these data indicate that TES functions as a necessary suppressor of colorectal cancer progression by activating p38-MAPK signaling pathways. (PMID:27323777)
• Testin plays an important role in the development and progression of non-small cell lung cancer. Testin is a tumor suppressor. (PMID:28000866)
• validated two new TES cocomplex partners: TGFB1I1 and a short form of the glucocorticoid receptor. TES and TGFB1I1 are shown to oppositely affect cell spreading providing biological validity for their copresence in complexes since they act in similar processes (PMID:28378594)
• testin region (amino acids 52-233) harbouring the PET domain interacts with the C-terminal LIM1-2 domains (PMID:28542564)
• Testin and filamin-C downregulation by acetylated Siah2 increases invasiveness of Helicobacter pylori-infected gastric cancer cells. (PMID:30063986)
• Expression of testin is downregulated in the hearts of patients with dilated cardiomyopathy. (PMID:30467953)
• These findings provide a better understanding of the development and progression of gastric cancer (GC) and indicate that TES may be used as a potential prognostic marker and therapeutic target for GC patients. (PMID:30728082)
• TES-mediated upregulation of the transcription factor DDIT3 is involved in CFP suppression of breast cancer cell growth (PMID:30755730)
• Chitinase 3-Like 1, Nestin, and Testin Proteins as Novel Biomarkers of Potential Clinical Use in Colorectal Cancer: A Review. (PMID:32170669)
• Stress fiber strain recognition by the LIM protein testin is cryptic and mediated by RhoA. (PMID:34038160)
• The value of lung function assessment and Testin expression detection in clinicopathological features and prognosis of NSCLC patients. (PMID:38627776)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	tes	ENSDARG00000051857
mus_musculus	Tes	ENSMUSG00000029552
mus_musculus	Tesl1	ENSMUSG00000068113
rattus_norvegicus	Tesl2	ENSRNOG00000013698
rattus_norvegicus	Tesl	ENSRNOG00000033628
rattus_norvegicus	Tes	ENSRNOG00000051952
rattus_norvegicus	Tesl1	ENSRNOG00000057692
rattus_norvegicus		ENSRNOG00000067513
drosophila_melanogaster	Tes	FBGN0034223
caenorhabditis_elegans		WBGENE00004112
caenorhabditis_elegans		WBGENE00015217

Paralogs (3): LMCD1 (ENSG00000071282), LIMD2 (ENSG00000136490), PRICKLE1 (ENSG00000139174)

Protein

Protein identifiers

Testin — Q9UGI8 (reviewed: Q9UGI8)

Alternative names: TESS

All UniProt accessions (5): A4D0U5, F8W7T0, F8WDI4, Q9UGI8, H7BYK1

UniProt curated annotations — full annotation on UniProt →

Function. Scaffold protein that may play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton. Plays a role in the regulation of cell proliferation. May act as a tumor suppressor. Inhibits tumor cell growth.

Subunit / interactions. Interacts via LIM domain 1 with ZYX. Interacts (via LIM domain 3) with ENAH and VASP. Interacts with ALKBH4, talin, actin, alpha-actinin, GRIP1 and PXN. Interacts (via LIM domain 2) with ACTL7A (via N-terminus). Heterodimer with ACTL7A; the heterodimer interacts with ENAH to form a heterotrimer.

Subcellular location. Cytoplasm. Cell junction. Focal adhesion.

Tissue specificity. Ubiquitous.

Domain organisation. The N-terminal and the C-terminal halves of the protein can associate with each other, thereby hindering interactions with ZYX.

Similarity. Belongs to the prickle / espinas / testin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UGI8-1	1	yes
Q9UGI8-2	2

RefSeq proteins (2): NP_056456, NP_690042 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR010442	PET_domain	Domain
IPR033724	PET_testin	Domain
IPR034958	LIM1_Testin	Domain
IPR034959	LIM2_Testin	Domain
IPR034960	LIM3_Testin	Domain
IPR047120	Pk/Esn/Tes	Family

Pfam: PF00412, PF06297

UniProt features (30 total): strand 10, turn 5, domain 4, helix 3, mutagenesis site 2, chain 1, sequence conflict 1, region of interest 1, compositionally biased region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2IYB	X-RAY DIFFRACTION	2.35
2XQN	X-RAY DIFFRACTION	2.62

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UGI8-F1	85.97	0.68

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
391	abolishes localization at focal adhesions.
328	abolishes interaction with actl7a.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 269 (showing top): LI_CISPLATIN_RESISTANCE_DN, TSENG_IRS1_TARGETS_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, CTATGCA_MIR153, NAGASHIMA_NRG1_SIGNALING_UP, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, LYF1_01, GUO_HEX_TARGETS_UP, IK2_01, VANTVEER_BREAST_CANCER_ESR1_DN

GO Biological Process (1): negative regulation of cell population proliferation (GO:0008285)

GO Molecular Function (5): RNA binding (GO:0003723), zinc ion binding (GO:0008270), cadherin binding (GO:0045296), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleus (GO:0005634), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cell junction (GO:0030054), protein-containing complex (GO:0032991), cytoplasm (GO:0005737), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
nucleic acid binding	1
transition metal ion binding	1
cell adhesion molecule binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
membrane	1
cell periphery	1
cell-substrate junction	1
cellular_component	1
intracellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

1052 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TES	LMO1	P25800	685
TES	VASP	P50552	632
TES	TLN1	Q9Y490	550
TES	SYP	P08247	549
TES	TLN2	Q9Y4G6	547
TES	ZYX	Q15942	530
TES	KCNE2	Q9Y6J6	509
TES	CASR	P41180	479
TES	SPTAN1	Q13813	446
TES	CYCS	P00001	424
TES	SDHC	Q99643	419
TES	IAH1	Q2TAA2	378
TES	ANKRD49	Q8WVL7	375
TES	STRN4	Q9NRL3	357
TES	ERMP1	Q7Z2K6	348

IntAct

101 interactions, top by confidence:

A	B	Type	Score
ZSCAN32	ZNF24	psi-mi:“MI:0914”(association)	0.880
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TES	ACTL7A	psi-mi:“MI:0915”(physical association)	0.670
TES	ACTL7A	psi-mi:“MI:0407”(direct interaction)	0.670
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
TES	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
TES	ENAH	psi-mi:“MI:0407”(direct interaction)	0.540
TES	ENAH	psi-mi:“MI:0915”(physical association)	0.540
ZSCAN32	ZNF197	psi-mi:“MI:0914”(association)	0.530
KPTN	EIF4G3	psi-mi:“MI:0914”(association)	0.530
RDH12	NME2P1	psi-mi:“MI:0914”(association)	0.530
CTNNA1	CTNNA2	psi-mi:“MI:0914”(association)	0.530
RNF135	XRCC4	psi-mi:“MI:0914”(association)	0.530
SNN	MTDH	psi-mi:“MI:0914”(association)	0.530
GORASP1	PPP6R2	psi-mi:“MI:0914”(association)	0.530

BioGRID (399): TES (Affinity Capture-RNA), TES (Affinity Capture-RNA), TES (Affinity Capture-MS), TES (Affinity Capture-MS), TES (Affinity Capture-MS), TES (Affinity Capture-MS), TES (Co-fractionation), TES (Co-fractionation), TES (Co-fractionation), TES (Co-fractionation), TES (Co-fractionation), TES (Proximity Label-MS), TES (Affinity Capture-MS), TES (Affinity Capture-MS), TES (Affinity Capture-MS)

ESM2 similar proteins: A0M8R4, A0M8S5, A0M8U6, A8K855, O00151, P47226, P52944, P60670, Q00PK1, Q07DW1, Q07DX3, Q07DY3, Q07DZ4, Q07E27, Q07E40, Q07E51, Q09YI0, Q09YJ2, Q09YK3, Q09YL5, Q09YN8, Q0E908, Q108U9, Q17QE2, Q2IBA3, Q2IBC3, Q2IBH0, Q2LAP6, Q2QL92, Q2QLA1, Q2QLB2, Q2QLC3, Q2QLE3, Q2QLF4, Q2QLG8, Q2QLH9, Q2YDE9, Q5PXT2, Q5RC52, Q6DIR5

Diamond homologs: A0A1L8F1M4, A0M8R4, A0M8S5, A0M8U6, A1Z6W3, A8WH69, O43294, O43900, P47226, Q00PK1, Q04650, Q07DW1, Q07DX3, Q07DY3, Q07DZ4, Q07E27, Q07E40, Q07E51, Q09YI0, Q09YJ2, Q09YK3, Q09YL5, Q09YN8, Q108U9, Q174I2, Q17QE2, Q28FG2, Q292U2, Q292U5, Q2IBA3, Q2IBC3, Q2IBH0, Q2LAP6, Q2QL92, Q2QLA1, Q2QLB2, Q2QLC3, Q2QLE3, Q2QLF4, Q2QLG8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 105 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
Transcriptional regulation of granulopoiesis	6	11.9×	3e-03
Regulation of PD-L1(CD274) transcription	5	8.6×	9e-03
Signaling by Interleukins	8	8.2×	3e-03
RAF/MAP kinase cascade	7	6.8×	6e-03
Cellular responses to stress	9	5.3×	5e-03
Cytokine Signaling in Immune system	8	5.2×	7e-03
Cellular responses to stimuli	9	4.5×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	7	24.2×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	41
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2685262	GRCh37/hg19 7q31.1-31.2(chr7:108967155-116850770)x1	Pathogenic

SpliceAI

1088 predictions. Top by Δscore:

Variant	Effect	Δscore
7:116249011:A:G	acceptor_gain	1.0000
7:116249018:A:AG	acceptor_gain	1.0000
7:116249019:G:GG	acceptor_gain	1.0000
7:116249019:GAA:G	acceptor_gain	1.0000
7:116249232:T:G	donor_gain	1.0000
7:116250493:ATAT:A	donor_gain	1.0000
7:116250493:ATATG:A	donor_loss	1.0000
7:116250494:TAT:T	donor_gain	1.0000
7:116250495:ATGT:A	donor_loss	1.0000
7:116250496:TGTA:T	donor_loss	1.0000
7:116250497:G:GA	donor_loss	1.0000
7:116250497:G:GG	donor_gain	1.0000
7:116250498:TAA:T	donor_loss	1.0000
7:116252520:GACT:G	donor_gain	1.0000
7:116210730:AGAAG:A	donor_loss	0.9900
7:116210731:GAAG:G	donor_gain	0.9900
7:116210732:AAG:A	donor_loss	0.9900
7:116210733:AGGTA:A	donor_loss	0.9900
7:116210734:GGT:G	donor_loss	0.9900
7:116210735:G:GA	donor_loss	0.9900
7:116234617:G:GT	donor_gain	0.9900
7:116249010:A:AG	acceptor_gain	0.9900
7:116249012:A:AG	acceptor_gain	0.9900
7:116249016:ATAGA:A	acceptor_loss	0.9900
7:116249017:T:G	acceptor_gain	0.9900
7:116249017:TAG:T	acceptor_loss	0.9900
7:116249018:A:AC	acceptor_loss	0.9900
7:116249019:GA:G	acceptor_gain	0.9900
7:116249019:GAAA:G	acceptor_gain	0.9900
7:116249019:GAAAA:G	acceptor_gain	0.9900

AlphaMissense

2829 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:116234570:T:C	C22R	1.000
7:116234572:T:G	C22W	1.000
7:116234615:T:A	W37R	1.000
7:116234615:T:C	W37R	1.000
7:116234619:G:C	R38T	1.000
7:116249027:T:C	C41R	1.000
7:116249028:G:A	C41Y	1.000
7:116249029:T:G	C41W	1.000
7:116249036:T:A	C44S	1.000
7:116249036:T:C	C44R	1.000
7:116249037:G:C	C44S	1.000
7:116249243:T:A	W113R	1.000
7:116249243:T:C	W113R	1.000
7:116249245:G:C	W113C	1.000
7:116249245:G:T	W113C	1.000
7:116250231:G:C	R146P	1.000
7:116250255:T:C	L154P	1.000
7:116251922:T:C	C289R	1.000
7:116251958:T:C	C301R	1.000
7:116251960:T:G	C301W	1.000
7:116251968:G:A	C304Y	1.000
7:116252381:T:C	C328R	1.000
7:116252383:C:G	C328W	1.000
7:116234570:T:A	C22S	0.999
7:116234571:G:A	C22Y	0.999
7:116234571:G:C	C22S	0.999
7:116234591:T:A	C29S	0.999
7:116234591:T:C	C29R	0.999
7:116234592:G:C	C29S	0.999
7:116234617:G:C	W37C	0.999

dbSNP variants (sampled 300 via entrez): RS1000083806 (7:116259246 C>T), RS1000092571 (7:116213978 T>C), RS1000148851 (7:116238940 G>T), RS1000178762 (7:116238644 C>T), RS1000231006 (7:116234154 T>A), RS1000267428 (7:116240772 T>G), RS1000361044 (7:116227734 A>T), RS1000466908 (7:116251097 G>T), RS1000483979 (7:116240453 TTCTC>T,TTC,TTCTCTC), RS1000498050 (7:116232870 T>A), RS1000613634 (7:116246314 A>C,G), RS1000683713 (7:116244920 G>A), RS1000765 (7:116224412 A>G), RS1000800055 (7:116252353 C>A,T), RS1000917492 (7:116252670 T>G)

Disease associations

OMIM: gene MIM:606085 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST005170_3	Intraocular pressure	2.000000e-20
GCST006394_13	Intraocular pressure	2.000000e-21
GCST006395_9	Glaucoma	5.000000e-06
GCST007576_200	Chronotype	8.000000e-09
GCST009391_874	Metabolite levels	6.000000e-07
GCST009725_16	Intraocular pressure	3.000000e-17
GCST009726_9	Glaucoma	8.000000e-07
GCST012292_12	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	8.000000e-06
GCST012297_3	Schizophrenia, bipolar disorder or major depressive disorder	9.000000e-06
GCST012298_11	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	6.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0008328	chronotype measurement
EFO:0006523	symmetrical dimethylarginine measurement
EFO:0004952	disease recurrence
EFO:0008343	sex interaction measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465364 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, increases expression, affects expression	8
Estradiol	affects cotreatment, decreases expression, increases expression	4
Cyclosporine	increases expression	4
methylmercuric chloride	increases expression, affects cotreatment	3
bisphenol A	decreases expression, decreases methylation, increases expression	3
trichostatin A	increases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Benzo(a)pyrene	decreases expression, increases expression	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
arsenite	decreases methylation	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5338466	Binding	Binding affinity to Tes (unknown origin) assessed as fold change in protein upregulation at 200 uM preincubated for 2 hrs followed by pronase addition and measured after 30 mins by coomassie blue staining based SDS-PAGE gel analysis	Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans. — J Nat Prod

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome