TRIT1

tRNA isopentenyltransferase 1

Basic information

Region (hg38): 1:39838109-39883511

Links

ENSG00000043514 ∙ NCBI:54802 ∙ OMIM:617840 ∙ HGNC:20286 ∙ Uniprot:Q9H3H1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation deficiency 35 (Strong), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 35	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	28185376; 24901367

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRIT1 gene.

• not provided (73 variants)
• Combined oxidative phosphorylation deficiency 35 (21 variants)
• Inborn genetic diseases (17 variants)
• TRIT1 Deficiency (6 variants)
• Epileptic encephalopathy (1 variants)
• TRIT1-related condition (1 variants)
• Macrocephaly (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRIT1 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				4	1	5
missense	1	2	39	3	2	47
nonsense	3	2				5
start loss						0
frameshift	1	3				4
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			3	3	1	7
non coding			2	12	8	22
Total	5	8	42	19	11

Highest pathogenic variant AF is 0.0000197

Variants in TRIT1

This is a list of pathogenic ClinVar variants found in the TRIT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-39841750-G-A			Likely benign (Apr 08, 2022)
1-39841838-A-G		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
1-39841847-A-C		Inborn genetic diseases	Uncertain significance (Sep 25, 2023)
1-39841858-G-A			Likely benign (Jun 01, 2022)
1-39841863-A-G			Likely benign (Jan 13, 2024)
1-39841892-T-G		TRIT1 Deficiency • Combined oxidative phosphorylation deficiency 35	Uncertain significance (Oct 15, 2018)
1-39841912-C-T			Benign (Jul 10, 2023)
1-39841913-G-A			Uncertain significance (Jul 19, 2022)
1-39841915-T-C		Combined oxidative phosphorylation deficiency 35	Likely pathogenic (-)
1-39842108-T-G			Likely benign (Jun 20, 2019)
1-39844089-C-T			Uncertain significance (Jul 20, 2022)
1-39844103-G-A		Combined oxidative phosphorylation deficiency 35	Uncertain significance (Jul 26, 2022)
1-39844104-C-A			Uncertain significance (Oct 14, 2022)
1-39844110-C-T			Likely pathogenic (Nov 14, 2023)
1-39844111-G-A		TRIT1-related disorder	Likely benign (Dec 02, 2021)
1-39844112-C-T			Uncertain significance (Nov 27, 2022)
1-39844120-AATG-A			Uncertain significance (Feb 07, 2020)
1-39844121-A-G		Combined oxidative phosphorylation deficiency 35	Uncertain significance (Nov 28, 2018)
1-39844131-G-A		TRIT1 Deficiency • Combined oxidative phosphorylation deficiency 35	Conflicting classifications of pathogenicity (Apr 15, 2021)
1-39844162-CTT-C		Combined oxidative phosphorylation deficiency 35	Pathogenic (Feb 05, 2024)
1-39844190-T-C		Inborn genetic diseases	Uncertain significance (Dec 12, 2023)
1-39844197-G-A		Inborn genetic diseases	Uncertain significance (Oct 29, 2021)
1-39844514-T-TCA			Likely benign (Jul 13, 2023)
1-39844523-A-G			Likely benign (Jul 22, 2023)
1-39844528-T-C			Uncertain significance (Jun 22, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRIT1	protein_coding	protein_coding	ENST00000316891	11	42461

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.09e-11	0.327	125413	0	335	125748	0.00133

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.783	227	263	0.864	0.0000136	3062
Missense in Polyphen		65	87.865	0.73977		1026
Synonymous	0.977	81	93.0	0.871	0.00000456	894
Loss of Function	1.01	19	24.4	0.780	0.00000136	267

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00141	0.00139
Ashkenazi Jewish	0.00	0.00
East Asian	0.000110	0.000109
Finnish	0.00246	0.00245
European (Non-Finnish)	0.00177	0.00175
Middle Eastern	0.000110	0.000109
South Asian	0.00120	0.00118
Other	0.00100	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the transfer of a dimethylallyl group onto the adenine at position 37 of both cytosolic and mitochondrial tRNAs, leading to the formation of N6-(dimethylallyl)adenosine (i(6)A). {ECO:0000269|PubMed:11111046, ECO:0000269|PubMed:24901367}.
• Disease: DISEASE: Combined oxidative phosphorylation deficiency 35 (COXPD35) [MIM:617873]: An autosomal recessive disorder caused by defective mitochondrial metabolism and deficiencies of mitochondrial respiratory enzyme complexes. Clinical manifestations include global developmental delay, intellectual disability, microcephaly, and early-onset seizures. {ECO:0000269|PubMed:24901367, ECO:0000269|PubMed:28185376}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: tRNA modification in the nucleus and cytosol;tRNA processing;tRNA modification in the mitochondrion;Metabolism of RNA (Consensus)

Recessive Scores

• pRec: 0.144

Intolerance Scores

• loftool: 0.904
• rvis_EVS: 0
• rvis_percentile_EVS: 53.73

Haploinsufficiency Scores

• pHI: 0.236
• hipred: N
• hipred_score: 0.174
• ghis: 0.543

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.578

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trit1

Gene ontology

• Biological process: tRNA modification;mitochondrial tRNA modification
• Cellular component: cellular_component;mitochondrion;mitochondrial matrix
• Molecular function: nucleic acid binding;ATP binding;zinc ion binding;tRNA dimethylallyltransferase activity