TRIP13

thyroid hormone receptor interactor 13, the group of AAA ATPases

Basic information

Region (hg38): 5:892883-919357

Links

ENSG00000071539 ∙ NCBI:9319 ∙ OMIM:604507 ∙ HGNC:12307 ∙ Uniprot:Q15645 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• female infertility due to oocyte meiotic arrest (Moderate), mode of inheritance: AR
• kidney Wilms tumor (Supportive), mode of inheritance: AD
• mosaic variegated aneuploidy syndrome (Supportive), mode of inheritance: AD
• mosaic variegated aneuploidy syndrome 3 (Limited), mode of inheritance: AR
• oocyte maturation defect 9 (Limited), mode of inheritance: AR
• oocyte maturation defect 9 (Strong), mode of inheritance: AR
• mosaic variegated aneuploidy syndrome 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mosaic variegated aneuploidy syndrome 3	AR	Oncologic	Individuals have been descriebd as susceptible to early-onset Wilms tumor, and awareness may allow early diagnosis and management	Craniofacial; Musculoskeletal; Neurologic; Obstetric; Oncologic; Ophthalmologic	28553959; 32473092
Increased susceptibility to other types of cancer has been suggested

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRIP13 gene.

• not provided (65 variants)
• Inborn genetic diseases (9 variants)
• Mosaic variegated aneuploidy syndrome 3 (5 variants)
• TRIP13-related condition (2 variants)
• Oocyte maturation defect 9 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRIP13 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				11	4	15
missense			14	2	1	17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1	1	1	3
non coding				1	42	43
Total	0	0	15	14	47

Variants in TRIP13

This is a list of pathogenic ClinVar variants found in the TRIP13 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-893049-G-A		TRIP13-related disorder	Likely benign (Dec 31, 2021)
5-893075-A-G		Oocyte maturation defect 9	Pathogenic (Apr 10, 2023)
5-893080-C-A		not specified	Uncertain significance (Nov 24, 2023)
5-893096-C-G		TRIP13-related disorder	Conflicting classifications of pathogenicity (Dec 22, 2023)
5-893101-C-A			Likely benign (Dec 02, 2023)
5-893106-C-G			Benign (Jan 27, 2024)
5-893106-C-T			Benign (Feb 01, 2024)
5-893107-C-T			Likely benign (Nov 15, 2023)
5-893241-C-G			Benign (Jun 14, 2019)
5-893310-C-G			Benign (Jun 15, 2019)
5-894817-T-C		TRIP13-related disorder	Likely benign (Feb 03, 2022)
5-894917-A-G		not specified	Uncertain significance (Jan 19, 2024)
5-894938-G-A			Uncertain significance (Jan 05, 2024)
5-894996-CA-C		Mosaic variegated aneuploidy syndrome 3 • Oocyte maturation defect 9	Benign (Sep 10, 2021)
5-896429-C-T			Benign (Jun 15, 2019)
5-896542-G-T			Benign (Jun 15, 2019)
5-896611-C-G			Benign (Jun 15, 2019)
5-896670-C-T			Uncertain significance (Nov 28, 2023)
5-896681-C-A		not specified	Uncertain significance (Dec 05, 2022)
5-896683-T-C		TRIP13-related disorder	Benign (Jan 20, 2024)
5-896754-A-G			Likely benign (Nov 23, 2023)
5-896867-C-CG			Benign (Jun 27, 2019)
5-896868-A-G			Benign (Jun 15, 2019)
5-900526-T-C		not specified	Uncertain significance (Feb 03, 2022)
5-900528-C-T		TRIP13-related disorder	Likely benign (Dec 17, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRIP13	protein_coding	protein_coding	ENST00000166345	13	26715

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.996	0.00394	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.32	141	243	0.581	0.0000131	2832
Missense in Polyphen		14	61.596	0.22729		688
Synonymous	-0.907	113	101	1.11	0.00000619	830
Loss of Function	4.28	2	25.2	0.0795	0.00000132	279

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000266	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000328	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 (By similarity). Plays a role in mitotic spindle assembly checkpoint (SAC) activation (PubMed:28553959). {ECO:0000250|UniProtKB:Q3UA06, ECO:0000269|PubMed:28553959}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:28553959}. Note=The disease is caused by mutations affecting the gene represented in this entry. MVA3 is caused by biallelic mutations in the TRIP13 gene.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase (Consensus)

Recessive Scores

• pRec: 0.123

Intolerance Scores

• loftool: 0.108
• rvis_EVS: -0.23
• rvis_percentile_EVS: 37.32

Haploinsufficiency Scores

• pHI: 0.418
• hipred: Y
• hipred_score: 0.825
• ghis: 0.644

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trip13
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; vision/eye phenotype; limbs/digits/tail phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype

Gene ontology

• Biological process: oocyte maturation;double-strand break repair;transcription by RNA polymerase II;mitotic spindle assembly checkpoint;synaptonemal complex assembly;reciprocal meiotic recombination;male meiosis I;female meiosis I;spermatogenesis;spermatid development;oogenesis;meiotic recombination checkpoint;regulation of nucleic acid-templated transcription
• Cellular component: male germ cell nucleus;nucleus;chromosome
• Molecular function: transcription coregulator activity;protein binding;ATP binding;identical protein binding