TRIP13

Summary

TRIP13 (thyroid hormone receptor interactor 13, HGNC:12307) is a protein-coding gene on chromosome 5p15.33, encoding Pachytene checkpoint protein 2 homolog (Q15645). Plays a key role in chromosome recombination and chromosome structure development during meiosis. It is a selective cancer dependency (DepMap: 15.1% of cell lines).

This gene encodes a protein that interacts with thyroid hormone receptors, also known as hormone-dependent transcription factors. The gene product interacts specifically with the ligand binding domain. This gene is one of several that may play a role in early-stage non-small cell lung cancer.

Source: NCBI Gene 9319 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mosaic variegated aneuploidy syndrome 3 (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 238 total — 6 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 105
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 15.1% of screened cell lines
• MANE Select transcript: NM_004237

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12307
Approved symbol	TRIP13
Name	thyroid hormone receptor interactor 13
Location	5p15.33
Locus type	gene with protein product
Status	Approved
Aliases	16E1BP
Ensembl gene	ENSG00000071539
Ensembl biotype	protein_coding
OMIM	604507
Entrez	9319

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding_CDS_not_defined, 3 protein_coding, 1 retained_intron

ENST00000166345, ENST00000508430, ENST00000508456, ENST00000509210, ENST00000510412, ENST00000512024, ENST00000513435, ENST00000891004

RefSeq mRNA: 2 — MANE Select: NM_004237 NM_001166260, NM_004237

CCDS: CCDS3858

Canonical transcript exons

ENST00000166345 — 13 exons

Exon	Start	End
ENSE00000719146	911843	911996
ENSE00000719150	908355	908461
ENSE00000852247	917008	918120
ENSE00001197868	914465	914577
ENSE00001958132	892884	893090
ENSE00003464181	904148	904220
ENSE00003507987	907130	907193
ENSE00003563483	901341	901431
ENSE00003629549	894787	894952
ENSE00003644787	900494	900549
ENSE00003657797	896665	896794
ENSE00003688286	915904	915973
ENSE00003784785	907988	908074

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 96.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.0221 / max 236.1388, expressed in 1490 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55509	19.7144	1480
55510	0.2119	95
55508	0.0958	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	96.92	gold quality
epithelium of bronchus	UBERON:0002031	96.16	gold quality
bronchus	UBERON:0002185	95.02	gold quality
endometrium epithelium	UBERON:0004811	94.62	gold quality
oocyte	CL:0000023	93.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.54	gold quality
secondary oocyte	CL:0000655	91.36	gold quality
right testis	UBERON:0004534	91.02	gold quality
left testis	UBERON:0004533	90.55	gold quality
ventricular zone	UBERON:0003053	90.16	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.91	gold quality
testis	UBERON:0000473	89.29	gold quality
sperm	CL:0000019	88.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.19	gold quality
male germ cell	CL:0000015	87.90	gold quality
embryo	UBERON:0000922	86.51	gold quality
ganglionic eminence	UBERON:0004023	86.35	gold quality
epithelium of nasopharynx	UBERON:0001951	84.58	gold quality
cortical plate	UBERON:0005343	82.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.27	gold quality
stromal cell of endometrium	CL:0002255	79.61	gold quality
adult organism	UBERON:0007023	78.97	gold quality
tongue squamous epithelium	UBERON:0006919	77.62	silver quality
rectum	UBERON:0001052	76.38	gold quality
lower esophagus mucosa	UBERON:0035834	75.87	gold quality
bone marrow	UBERON:0002371	75.21	gold quality
mucosa of transverse colon	UBERON:0004991	74.83	gold quality
amniotic fluid	UBERON:0000173	74.63	gold quality
bone marrow cell	CL:0002092	74.14	gold quality
esophagus mucosa	UBERON:0002469	74.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8530	yes	120.50
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting TRIP13, 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-656-3P	100.00	72.15	2788
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 15.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• suggest that premature mitotic checkpoint silencing triggered by TRIP13 overexpression may promote cancer development (PMID:25012665)
• TRIP13 promotes error-prone non-homologous end joining and induces chemoresistance in head and neck cancer. (PMID:25078033)
• propose that TRIP13 plays centrally important roles in the sequence of events leading to MCC disassembly and checkpoint inactivation (PMID:25092294)
• the oligomeric form of TRIP13 binds both p31(comet) and MCC (PMID:26324890)
• These results establish a paradigm of the roles of p31(comet) and TRIP13 in both checkpoint activation and inactivation. (PMID:26832417)
• TRIP13 ubiquitinates and degrades the checkpoint surveillance protein MAD2 via activating Akt signaling pathway, leading to weakened checkpoint surveillance and consequent tumorigenic aneuploidy and drug resistance in MM. (PMID:28157697)
• Microarray analyses indicated that the biological function of TRIP13 in CLL is majorly cell apoptosis and cell proliferation associated. TRIP13 siRNA expressing cells exhibited a slower cell proliferation rate and underwent apoptosis compared with control cells. (PMID:28424416)
• 6 individuals with biallelic loss-of-function mutations in TRIP13 developed Wilms tumors. TRIP13-mutant patient cells have no detectable TRIP13 and have substantial impairment of the spindle assembly checkpoint (SAC), leading to a high rate of chromosome missegregation. Individuals with biallelic TRIP13 mutations have a high risk of embryonal tumors. These experiments show that their cells display severe SAC impairment. (PMID:28553959)
• These results identify an unexpected dependency on TRIP13 in cells overexpressing Mad2. (PMID:28564602)
• Thes authors show that p31(comet) binding to the TRIP13 N-terminal domain positions the disordered MAD2 N-terminus for engagement by the TRIP13 “pore loops”, which then unfold MAD2 in the presence of ATP. (PMID:28659378)
• TRIP13 mRNA significantly over-expressed in chronic lymphocytic leukemia patients CD19(+) B lymphocytes (PMID:28810332)
• TRIP13-p31(comet) intercepts and disassembles free mitotic checkpoint complex not bound to anaphase-promoting complex/cyclosome through mediating the local unfolding of the Mad2 C-terminal region. (PMID:29208896)
• TRIP13 replenishes the O-MAD2 pool for activation by unattached kinetochores. (PMID:29425500)
• TRIP13 promoted colorectal cancer cell proliferation, invasion and migration. (PMID:29540729)
• heightened TRIP13 expression appears to promote lung adenocarcinoma tumor progression. (PMID:29567476)
• study provides insights into how specific substrates are recruited to AAA+ ATPases (like TRIP13) through adaptor proteins and suggests a model of how translocation through the axial pore of AAA+ ATPases is coupled to protein remodelling (PMID:29973720)
• TRIP13 is correlated with clinical progression and poor prognosis (PMID:30267820)
• Study revealed that the expression of TRIP13 was elevated in hepatocellular carcinoma (HCC). Furthermore, TRIP3 expression was correlated with cancer progression and malignancy. HCC patients with higher TRIP13 expression had significantly shorter survival periods compared with patients with lower TRIP13 expression. (PMID:30542731)
• miR-515-5p is down-regulated, and associated with the malignant status and prognosis in prostate cancer patients. MiR-515-5p acts as a tumor suppressor to regulate cell proliferation, migration and invasion via targeting TRIP13 in prostate cancer. (PMID:30685303)
• The TRIP13 acted as an onco-promotive regulator in epithelial ovarian cancer (EOC) development by modulating the Notch signaling pathway. (PMID:30720159)
• Our study demonstrated that TRIP13 might be a tumor promoting factor in esophageal squamous cell carcinoma (PMID:31064720)
• TRIP13 expression drives the tumorigenesis of bladder cancer in association with the EGFR signaling pathway (PMID:31337978)
• TRIP13 is correlated with poor prognosis of bladder cancer by promoting proliferation, invasion, and epithelial-mesenchymal transition. (PMID:31486418)
• High TRIP13 expression is associated with the progression of hepatocellular carcinoma. (PMID:31533816)
• Absence of the TRIP13 c.1060C>T Mutation in Wilms Tumor Patients From Pakistan. (PMID:31574018)
• TRIP13 interference inhibited the proliferation and metastasis of thyroid cancer cells through regulating TTC5/p53 pathway and epithelial-mesenchymal transition related genes expression. (PMID:31648166)
• our study indicated that the TRIP13/FBXW7/c-MYC pathway might provide a prospective therapeutic target in the treatment of glioblastoma (PMID:31740732)
• Bi-allelic Missense Pathogenic Variants in TRIP13 Cause Female Infertility Characterized by Oocyte Maturation Arrest. (PMID:32473092)
• Thyroid receptor-interacting protein 13 and EGFR form a feedforward loop promoting glioblastoma growth. (PMID:32860853)
• TRIP13 promotes metastasis of colorectal cancer regardless of p53 and microsatellite instability status. (PMID:33037736)
• p31(comet) promotes homologous recombination by inactivating REV7 through the TRIP13 ATPase. (PMID:33051298)
• TRIP13 promotes the proliferation and invasion of lung cancer cells via the Wnt signaling pathway and epithelial-mesenchymal transition. (PMID:33128167)
• TRIP13 promotes lung cancer cell growth and metastasis through AKT/mTORC1/c-Myc signaling. (PMID:33136091)
• Investigation of the expression levels of CPEB4, APC, TRIP13, EIF2S3, EIF4A1, IFNg, PIK3CA and CTNNB1 genes in different stage colorectal tumors (PMID:33237662)
• TRIP13 exerts a cancer-promoting role in cervical cancer by enhancing Wnt/beta-catenin signaling via ACTN4. (PMID:34061428)
• Upregulation of TRIP13 promotes the malignant progression of lung cancer via the EMT pathway. (PMID:34184074)
• MAD2L2 dimerization and TRIP13 control shieldin activity in DNA repair. (PMID:34521823)
• [Regulation of TRIP13 on Proliferation and Apoptosis of B-Cell Lymphoma Cells and Its Mechanism]. (PMID:34627428)
• TRIP13 knockdown inhibits the proliferation, migration, invasion, and promotes apoptosis by suppressing PI3K/AKT signaling pathway in U2OS cells. (PMID:35032258)
• Evaluation of the TRIP13 level in breast cancer and insights into potential molecular pathways. (PMID:35322916)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	trip13	ENSDARG00000025043
mus_musculus	Trip13	ENSMUSG00000021569
rattus_norvegicus	Trip13	ENSRNOG00000015810
drosophila_melanogaster	pch2	FBGN0051453

Protein

Protein identifiers

Pachytene checkpoint protein 2 homolog — Q15645 (reviewed: Q15645)

Alternative names: Human papillomavirus type 16 E1 protein-binding protein, Thyroid hormone receptor interactor 13, Thyroid receptor-interacting protein 13

All UniProt accessions (2): Q15645, H0YAL2

UniProt curated annotations — full annotation on UniProt →

Function. Plays a key role in chromosome recombination and chromosome structure development during meiosis. Required at early steps in meiotic recombination that leads to non-crossovers pathways. Also needed for efficient completion of homologous synapsis by influencing crossover distribution along the chromosomes affecting both crossovers and non-crossovers pathways. Also required for development of higher-order chromosome structures and is needed for synaptonemal-complex formation. In males, required for efficient synapsis of the sex chromosomes and for sex body formation. Promotes early steps of the DNA double-strand breaks (DSBs) repair process upstream of the assembly of RAD51 complexes. Required for depletion of HORMAD1 and HORMAD2 from synapsed chromosomes. Plays a role in mitotic spindle assembly checkpoint (SAC) activation.

Subunit / interactions. Specifically interacts with the ligand binding domain of the thyroid receptor (TR). This interaction does not require the presence of thyroid hormone for its interaction. Interacts with HPV16 E1. Interacts with proteasome subunit PSMA8; to participate in meiosis progression during spermatogenesis.

Disease relevance. Mosaic variegated aneuploidy syndrome 3 (MVA3) [MIM:617598] A form of mosaic variegated aneuploidy syndrome, a severe disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases. MVA3 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. MVA3 is caused by biallelic mutations in the TRIP13 gene. Oocyte/zygote/embryo maturation arrest 9 (OZEMA9) [MIM:619011] An autosomal recessive infertility disorder due to oocyte meiotic arrest at metaphase I. Abnormal zygotic cleavage has been observed in some patients. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the AAA ATPase family. PCH2 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15645-1	1	yes
Q15645-2	2

RefSeq proteins (2): NP_001159732, NP_004228* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001270	ClpA/B	Family
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR003960	ATPase_AAA_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR044539	Pch2-like	Family
IPR058249	Pch2_C	Domain

Pfam: PF00004, PF23242, PF23563

UniProt features (42 total): helix 15, strand 11, turn 6, sequence variant 6, chain 1, binding site 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5WC2	X-RAY DIFFRACTION	2.5
5VQA	X-RAY DIFFRACTION	2.54
6LK0	X-RAY DIFFRACTION	2.6
5VQ9	X-RAY DIFFRACTION	3.02
7L9P	ELECTRON MICROSCOPY	3.6
6F0X	ELECTRON MICROSCOPY	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15645-F1	86.94	0.64

Functional residue map

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

Ligand- & substrate-binding residues (1): 179–186

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 636 (showing top): GNF2_CKS1B, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MODULE_52, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, HORIUCHI_WTAP_TARGETS_DN, GOBP_REGULATION_OF_NUCLEAR_DIVISION, BASSO_B_LYMPHOCYTE_NETWORK, PAL_PRMT5_TARGETS_UP, CROONQUIST_NRAS_SIGNALING_DN, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN

GO Biological Process (14): oocyte maturation (GO:0001556), double-strand break repair (GO:0006302), transcription by RNA polymerase II (GO:0006366), mitotic spindle assembly checkpoint signaling (GO:0007094), synaptonemal complex assembly (GO:0007130), reciprocal meiotic recombination (GO:0007131), male meiosis I (GO:0007141), female meiosis I (GO:0007144), spermatogenesis (GO:0007283), spermatid development (GO:0007286), oogenesis (GO:0048477), meiotic recombination checkpoint signaling (GO:0051598), cell differentiation (GO:0030154), meiotic cell cycle (GO:0051321)

GO Molecular Function (6): transcription coregulator activity (GO:0003712), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (3): male germ cell nucleus (GO:0001673), nucleus (GO:0005634), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
meiosis I	3
developmental process involved in reproduction	2
male gamete generation	2
meiotic cell cycle	2
female gamete generation	2
germ cell development	2
cell maturation	1
oocyte development	1
DNA repair	1
DNA-templated transcription	1
mitotic cell cycle	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
homologous chromosome pairing at meiosis	1
cellular component assembly	1
chromosome organization involved in meiotic cell cycle	1
synaptonemal complex organization	1
reciprocal homologous recombination	1
meiotic cell cycle process	1
male meiotic nuclear division	1
female meiotic nuclear division	1
spermatid differentiation	1
meiotic cell cycle checkpoint signaling	1
negative regulation of meiotic nuclear division	1
cellular developmental process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
transcription regulator activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
germ cell nucleus	1

Protein interactions and networks

STRING

3727 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIP13	MAD2L1BP	Q15013	876
TRIP13	MAD2L2	Q9UI95	759
TRIP13	CDC20	Q12834	735
TRIP13	HORMAD1	Q86X24	726
TRIP13	HORMAD2	Q8N7B1	688
TRIP13	SPO11	Q9Y5K1	688
TRIP13	UBE2C	O00762	673
TRIP13	CEP57	Q86XR8	670
TRIP13	TXNRD2	Q9NNW7	651
TRIP13	THRB	P10828	626
TRIP13	TOP2A	P11388	607
TRIP13	FOXM1	Q08050	604
TRIP13	BUB3	O43684	594
TRIP13	BUB1B	O60566	576
TRIP13	TK1	P04183	550

IntAct

553 interactions, top by confidence:

A	B	Type	Score
ARSA	TRIP13	psi-mi:“MI:0915”(physical association)	0.900
TRIP13	ARSA	psi-mi:“MI:0915”(physical association)	0.900
MAD2L1BP	TRIP13	psi-mi:“MI:0915”(physical association)	0.870
TRIP13	GLYCTK	psi-mi:“MI:0915”(physical association)	0.840
GLYCTK	TRIP13	psi-mi:“MI:0915”(physical association)	0.840
TRIP13	LNX1	psi-mi:“MI:0915”(physical association)	0.830
LNX1	TRIP13	psi-mi:“MI:0915”(physical association)	0.830
TRIP13	LASP1	psi-mi:“MI:0915”(physical association)	0.820
LASP1	TRIP13	psi-mi:“MI:0915”(physical association)	0.820
TRIP13	TRIP13	psi-mi:“MI:0915”(physical association)	0.800
MPPED2	TRIP13	psi-mi:“MI:0915”(physical association)	0.790
TRIP13	RHOXF2	psi-mi:“MI:0915”(physical association)	0.790
TRIP13	MPPED2	psi-mi:“MI:0915”(physical association)	0.790
C4orf33	TRIP13	psi-mi:“MI:0915”(physical association)	0.780
TRIP13	SPMIP9	psi-mi:“MI:0915”(physical association)	0.780
PLSCR3	TRIP13	psi-mi:“MI:0915”(physical association)	0.780
TRIP13	C4orf33	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (396): TRIP13 (Two-hybrid), TRIP13 (Two-hybrid), TRIP13 (Two-hybrid), TRIP13 (Two-hybrid), TRIP13 (Two-hybrid), TRIP13 (Two-hybrid), TRIP13 (Two-hybrid), TRIP13 (Two-hybrid), TRIP13 (Two-hybrid), TRIP13 (Two-hybrid), DPYSL4 (Two-hybrid), DIP2A (Two-hybrid), TNRC6A (Two-hybrid), AMDHD2 (Two-hybrid), CYB5R2 (Two-hybrid)

ESM2 similar proteins: A0JMG1, A2VE52, D3K5L7, E0CZ16, E1C6Q1, E2R222, F1LZ52, F1LZF0, F1MBP6, O13016, O35345, O43791, O60684, O95164, O95198, O95544, P35815, P36993, P54797, P58058, P63143, P63144, Q0IHH9, Q0V7M0, Q0VCW1, Q15645, Q28528, Q28F89, Q2M2N2, Q2TA46, Q3UA06, Q4PJK1, Q5BL35, Q5NVK7, Q5RBV0, Q5REP9, Q5U1X1, Q5XHZ9, Q6GR09, Q6IQ16

Diamond homologs: A0JWY3, A2XUN8, A4QE83, A9RA82, B1VDV2, B1ZMG6, B3EX35, B3M301, B3P8A3, B4HGG6, B4JII0, B4M0H8, B4NBP4, B4PL32, B4QSF0, B4USW8, B6YXR2, B7NZ88, B8DTX4, B8H8L3, C3PGA0, C5A6P8, C6A7B2, C6AHX0, C7LYP4, C7MCZ0, D2VS83, D3K5L7, D3R4I7, E1C6Q1, E2R222, O05209, O14325, O15381, O16299, O43078, O57940, O61577, P03974, P0DTF4

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
EGFR	“up-regulates quantity”	TRIP13	phosphorylation
TRIP13	“up-regulates quantity by stabilization”	EGFR	binding
MAD2L1BP	“up-regulates activity”	TRIP13	binding
TRIP13	“down-regulates quantity by destabilization”	MCC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 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.

GO biological processes:

GO term	Partners	Fold	FDR
response to oxidative stress	6	11.4×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	3
Uncertain significance	83
Likely benign	78
Benign	55

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
3723852	NM_004237.4(TRIP13):c.720_723del (p.Ile240fs)	Pathogenic
431045	NM_004237.4(TRIP13):c.1060C>T (p.Arg354Ter)	Pathogenic
431046	NM_004237.4(TRIP13):c.673-1G>C	Pathogenic
977642	NM_004237.4(TRIP13):c.518G>A (p.Arg173Gln)	Pathogenic
977644	NM_004237.4(TRIP13):c.592A>G (p.Ile198Val)	Pathogenic
977645	NM_004237.4(TRIP13):c.739G>A (p.Val247Met)	Pathogenic
3645934	NM_004237.4(TRIP13):c.672+1G>A	Likely pathogenic
3910602	NM_004237.4(TRIP13):c.420dup (p.Tyr141fs)	Likely pathogenic
4070948	NM_004237.4(TRIP13):c.1021-1G>C	Likely pathogenic

SpliceAI

2091 predictions. Top by Δscore:

Variant	Effect	Δscore
5:894784:TA:T	acceptor_loss	1.0000
5:894785:A:AG	acceptor_gain	1.0000
5:894786:G:GG	acceptor_gain	1.0000
5:894786:GC:G	acceptor_gain	1.0000
5:894786:GCA:G	acceptor_gain	1.0000
5:894786:GCAC:G	acceptor_gain	1.0000
5:894786:GCACT:G	acceptor_gain	1.0000
5:894951:AGGTA:A	donor_loss	1.0000
5:894952:GGTA:G	donor_loss	1.0000
5:894953:G:C	donor_loss	1.0000
5:896663:A:AG	acceptor_gain	1.0000
5:896664:G:GG	acceptor_gain	1.0000
5:901339:A:AG	acceptor_gain	1.0000
5:901340:G:GG	acceptor_gain	1.0000
5:901461:A:G	donor_gain	1.0000
5:907190:GGAA:G	donor_gain	1.0000
5:907191:GAAG:G	donor_gain	1.0000
5:907194:G:GG	donor_gain	1.0000
5:907986:A:AG	acceptor_gain	1.0000
5:907986:AGAGT:A	acceptor_gain	1.0000
5:907987:G:GG	acceptor_gain	1.0000
5:907987:GA:G	acceptor_gain	1.0000
5:907987:GAGT:G	acceptor_gain	1.0000
5:907987:GAGTG:G	acceptor_gain	1.0000
5:911831:C:A	acceptor_gain	1.0000
5:911992:TGAAG:T	donor_loss	1.0000
5:911995:AGGT:A	donor_loss	1.0000
5:911996:GGTA:G	donor_loss	1.0000
5:911997:G:C	donor_loss	1.0000
5:911998:T:A	donor_loss	1.0000

AlphaMissense

2848 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:904163:G:A	G184E	1.000
5:907185:T:C	F222L	1.000
5:907187:T:A	F222L	1.000
5:907187:T:G	F222L	1.000
5:908430:G:C	A279P	1.000
5:900511:T:A	W136R	0.999
5:900511:T:C	W136R	0.999
5:904157:G:A	G182D	0.999
5:904162:G:A	G184R	0.999
5:904162:G:C	G184R	0.999
5:904163:G:T	G184V	0.999
5:904166:A:T	K185I	0.999
5:904169:C:T	T186I	0.999
5:904179:T:G	C189W	0.999
5:904190:C:A	A193D	0.999
5:907161:A:C	S214R	0.999
5:907163:C:A	S214R	0.999
5:907163:C:G	S214R	0.999
5:907988:A:C	S225R	0.999
5:907990:T:A	S225R	0.999
5:907990:T:G	S225R	0.999
5:908064:T:C	L250P	0.999
5:908070:A:C	D252A	0.999
5:908070:A:T	D252V	0.999
5:908073:A:C	E253A	0.999
5:908073:A:T	E253V	0.999
5:908361:A:C	S256R	0.999
5:908363:T:A	S256R	0.999
5:908363:T:G	S256R	0.999
5:908437:T:C	L281S	0.999

dbSNP variants (sampled 300 via entrez): RS1000052388 (5:917823 G>C), RS1000080687 (5:902459 C>T), RS1000099469 (5:892611 T>C), RS1000122459 (5:916546 G>A), RS1000192567 (5:894648 T>C), RS1000196821 (5:902812 A>G), RS1000336418 (5:901060 C>T), RS1000457285 (5:907786 A>G,T), RS1000526066 (5:903646 G>A), RS1000578521 (5:903462 T>C,G), RS1000596435 (5:896525 C>A,T), RS1000697228 (5:891579 G>A,C,T), RS1000697387 (5:916931 C>G,T), RS1000980254 (5:891504 G>A,C), RS1001033934 (5:891293 C>A,T)

Disease associations

OMIM: gene MIM:604507 | disease phenotypes: MIM:617598, MIM:619011

GenCC curated gene-disease

Disease	Classification	Inheritance
mosaic variegated aneuploidy syndrome 3	Strong	Autosomal recessive
oocyte maturation defect 9	Strong	Autosomal recessive
female infertility due to oocyte meiotic arrest	Moderate	Autosomal recessive
mosaic variegated aneuploidy syndrome	Supportive	Autosomal dominant
kidney Wilms tumor	Supportive	Autosomal dominant

Mondo (5): mosaic variegated aneuploidy syndrome 3 (MONDO:0054736), oocyte maturation defect 9 (MONDO:0033565), mosaic variegated aneuploidy syndrome (MONDO:0000141), kidney Wilms tumor (MONDO:0019004), female infertility due to oocyte meiotic arrest (MONDO:0044626)

Orphanet (0):

HPO phenotypes

105 total (30 of 105 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000062	Ambiguous genitalia
HP:0000085	Horseshoe kidney
HP:0000086	Ectopic kidney
HP:0000140	Abnormality of the menstrual cycle
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000325	Triangular face
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000444	Convex nasal ridge
HP:0000445	Wide nose
HP:0000457	Depressed nasal ridge
HP:0000478	Abnormality of the eye
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000504	Abnormality of vision
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract
HP:0000526	Aniridia
HP:0000568	Microphthalmia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002553_8	Pancreatic cancer	1.000000e-13

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536987	Mosaic variegated aneuploidy syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465278 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 11 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.28	Kd	53.09	nM	CHEMBL5653589
7.28	ED50	53.09	nM	CHEMBL5653589
5.17	Kd	6800	nM	CHEMBL5619341
5.07	Kd	8600	nM	CHEMBL5395636

PubChem BioAssay actives

3 with measured affinity, of 33 total; 3 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	2149659: Binding affinity to human TRIP13 incubated for 45 mins by Kinobead based pull down assay	kd	0.0531	uM
[(2R,6R)-6-benzamido-3-(4-chlorophenyl)sulfanyl-5-oxooxan-2-yl]methyl acetate	2128599: Binding affinity to TRIP13 (unknown origin) assessed as dissociation constant by SPR analysis	kd	6.8000	uM
4-[4-(pyridin-4-ylmethyl)phenyl]-4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-ene-3,5-dione	2128599: Binding affinity to TRIP13 (unknown origin) assessed as dissociation constant by SPR analysis	kd	8.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases expression	4
bisphenol A	decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression, affects cotreatment	2
Estradiol	increases expression	2
Rotenone	decreases expression, increases expression	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
afuresertib	decreases expression	1
lasiocarpine	increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
potassium perchlorate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
phenethyl isothiocyanate	decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
2-palmitoylglycerol	increases expression	1
CPG-oligonucleotide	decreases expression	1
K 7174	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5358315	Binding	Inhibition of His-tagged TRIP13 (unknown origin) expressed in Escherichia coli using ATP as substrate preincubated for 30 mins followed by substrate addition and measured upto 30 mins	Design and synthesis of cantharidin derivative DCZ5418 as a TRIP13 inhibitor with anti-multiple myeloma activity in vitro and in vivo. — Bioorg Med Chem Lett

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3K5	Abcam HEK293T TRIP13 KO 1	Transformed cell line	Female
CVCL_B3K6	Abcam HEK293T TRIP13 KO 2	Transformed cell line	Female
CVCL_TU64	HAP1 TRIP13 (-) 1	Cancer cell line	Male
CVCL_XU72	HAP1 TRIP13 (-) 2	Cancer cell line	Male
CVCL_XU73	HAP1 TRIP13 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00336531	PHASE4	COMPLETED	Efficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation
NCT00352534	PHASE3	ACTIVE_NOT_RECRUITING	Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms’ Tumor
NCT00379340	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms’ Tumor
NCT00945009	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor
NCT00001509	PHASE2	COMPLETED	A Phase II Trial of All-Trans-Retinoic Acid in Combination With Interferon-Alpha 2a in Children With Recurrent Neuroblastoma or Wilms’ Tumor
NCT00038207	PHASE2	COMPLETED	Liposomal Vincristine for Pediatric and Adolescent Patients With Relapsed Malignancies
NCT00141765	PHASE2	COMPLETED	Study of High-Dose Chemotherapy With Bone Marrow or Stem Cell Transplant for Rare Poor-Prognosis Cancers
NCT00187031	PHASE2	COMPLETED	A Phase II Study of Topotecan in Children With Recurrent Wilms Tumor
NCT00335556	PHASE2	COMPLETED	Combination Chemotherapy, Radiation Therapy, and/or Surgery in Treating Patients With High-Risk Kidney Tumors
NCT01095926	PHASE2	COMPLETED	Pharmacokinetic Study of Doxorubicin in Children With Cancer
NCT02452554	PHASE2	COMPLETED	Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma
NCT02624388	PHASE2	TERMINATED	Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)
NCT02689336	PHASE2	WITHDRAWN	Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors
NCT02867592	PHASE2	ACTIVE_NOT_RECRUITING	Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	PHASE2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	PHASE2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04322318	PHASE2	RECRUITING	A Study of Combination Chemotherapy for Patients With Newly Diagnosed DAWT and Relapsed FHWT
NCT04791228	PHASE2	WITHDRAWN	A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors
NCT04968990	PHASE2	RECRUITING	Treatment of Newly Diagnosed Patient’s With Wilm’s Tumor Requiring Abdominal Radiation Delivered With Proton Beam Irradiation
NCT05302921	PHASE2	COMPLETED	Neoadjuvant Dual Checkpoint Inhibition and Cryoablation in Relapsed/Refractory Pediatric Solid Tumors
NCT05985161	PHASE2	RECRUITING	A Study of Selinexor in People With Wilms Tumors and Other Solid Tumors
NCT00011414	PHASE1	COMPLETED	Phase I Trial of Tariquidar (XR9576) in Combination With Doxorubicin, Vinorelbine, or Docetaxel in Pediatric Patients With Solid Tumors
NCT00436657	PHASE1	COMPLETED	Continuous Hyperthermic Peritoneal Perfusion (CHPP) With Cisplatin for Children With Peritoneal Cancer
NCT00931931	PHASE1	COMPLETED	HSV1716 in Patients With Non-Central Nervous System (Non-CNS) Solid Tumors
NCT01130623	PHASE1	WITHDRAWN	A Phase I Study of Pazopanib as a Single Agent for Children With Refractory Solid Tumors
NCT01222780	PHASE1	COMPLETED	To Evaluate the Safety, Activity and Pharmacokinetics of Marqibo in Children and Adolescents With Refractory Cancer
NCT01331135	PHASE1	COMPLETED	Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
NCT01625351	PHASE1	COMPLETED	A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas
NCT01661400	PHASE1	COMPLETED	Anti-Angiogenic Therapy Post Transplant (ASCR) for Pediatric Solid Tumors