GTPBP3

GTP binding protein 3, mitochondrial

Basic information

Region (hg38): 19:17334920-17342731

Links

ENSG00000130299 ∙ NCBI:84705 ∙ OMIM:608536 ∙ HGNC:14880 ∙ Uniprot:Q969Y2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation defect type 23 (Strong), mode of inheritance: AR
• combined oxidative phosphorylation defect type 23 (Supportive), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 23	AR	Cardiovascular	Among other multi-systemic manifestations, the condition may include cardiac manifestations such as hypertrophic cardiomyopathy, and surveillance may allow early diagnosis and management	Biochemical; Cardiovascular	25434004

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GTPBP3 gene.

• not provided (20 variants)
• Combined oxidative phosphorylation defect type 23 (3 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GTPBP3 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			5	121	3	129
missense	1	6	167	5	6	185
nonsense	6	2	1			9
start loss	1					1
frameshift	11	2	1			14
inframe indel			6			6
splice donor/acceptor (+/-2bp)						0
splice region		1	15	27	1	44
non coding	3		13	61	19	96
Total	22	10	193	187	28

Highest pathogenic variant AF is 0.0000328

Variants in GTPBP3

This is a list of pathogenic ClinVar variants found in the GTPBP3 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-17335001-C-T		GTPBP3-related disorder	Likely benign (Jul 30, 2019)
19-17335021-T-A		GTPBP3-related disorder	Likely benign (Oct 07, 2019)
19-17335027-C-T			Likely benign (Oct 05, 2018)
19-17335039-T-C			Likely benign (Aug 01, 2022)
19-17335046-G-C		GTPBP3-related disorder	Likely benign (Jun 01, 2020)
19-17335083-C-A		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
19-17337486-G-A			Benign (Jul 09, 2018)
19-17337596-C-G		not specified	Uncertain significance (Nov 04, 2022)
19-17337613-T-A			Pathogenic (Nov 28, 2015)
19-17337618-C-T			Uncertain significance (Jan 07, 2022)
19-17337618-CG-C		Inborn genetic diseases	Pathogenic (Nov 24, 2021)
19-17337619-G-A			Uncertain significance (May 12, 2022)
19-17337619-G-C		not specified	Uncertain significance (Sep 01, 2016)
19-17337619-G-T			Uncertain significance (Aug 23, 2022)
19-17337621-G-A			Uncertain significance (Jul 01, 2022)
19-17337622-G-T			Uncertain significance (Oct 30, 2023)
19-17337628-G-A		See cases	Pathogenic/Likely pathogenic (Aug 18, 2023)
19-17337640-C-T			Uncertain significance (Jul 15, 2022)
19-17337643-AA-GTG		Combined oxidative phosphorylation defect type 23	Pathogenic (Dec 04, 2014)
19-17337645-G-T			Uncertain significance (Aug 10, 2022)
19-17337646-C-A			Uncertain significance (Aug 20, 2021)
19-17337656-G-A		GTPBP3-related disorder	Likely benign (Aug 27, 2023)
19-17337669-G-C			Uncertain significance (Sep 01, 2022)
19-17337670-G-A			Uncertain significance (Apr 09, 2021)
19-17337674-C-G			Likely benign (Nov 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GTPBP3	protein_coding	protein_coding	ENST00000358792	8	7816

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.19e-9	0.356	125710	0	37	125747	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0108	343	342	1.00	0.0000222	3267
Missense in Polyphen		144	155.67	0.92505		1454
Synonymous	-0.425	171	164	1.04	0.0000114	1224
Loss of Function	0.826	15	18.9	0.795	0.00000106	188

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000551	0.000425
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000135	0.000132
Middle Eastern	0.000163	0.000163
South Asian	0.000261	0.000261
Other	0.000344	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: GTPase involved in the 5-carboxymethylaminomethyl modification (mnm(5)s(2)U34) of the wobble uridine base in mitochondrial tRNAs. {ECO:0000305}.
• Disease: DISEASE: Combined oxidative phosphorylation deficiency 23 (COXPD23) [MIM:616198]: An autosomal recessive mitochondrial disorder characterized by hypertrophic cardiomyopathy and/or neurologic symptoms with onset in early childhood. Disease features include hypertrophic cardiomyopathy, hypotonia, delayed psychomotor development, lactic acidosis, impaired activities of respiratory complexes I and IV, and defective translation of mitochondrial proteins. Disease severity is variable, ranging from death in early infancy to survival into the second decade of life. {ECO:0000269|PubMed:25434004, ECO:0000269|PubMed:26741492}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: miR-targeted genes in lymphocytes - TarBase (Consensus)

Recessive Scores

• pRec: 0.167

Intolerance Scores

• loftool: 0.548
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.44

Haploinsufficiency Scores

• pHI: 0.145
• hipred: N
• hipred_score: 0.428
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.900

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gtpbp3

Zebrafish Information Network

• Gene name: gtpbp3
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curved

Gene ontology

• Biological process: tRNA wobble uridine modification;tRNA methylation;embryonic organ development
• Cellular component: cytoplasm;mitochondrion
• Molecular function: GTPase activity;protein binding;GTP binding