TIMM50

translocase of inner mitochondrial membrane 50, the group of CTD family phosphatases

Basic information

Region (hg38): 19:39480412-39493785

Links

ENSG00000105197 ∙ NCBI:92609 ∙ OMIM:607381 ∙ HGNC:23656 ∙ Uniprot:Q3ZCQ8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 3-methylglutaconic aciduria type 9 (Strong), mode of inheritance: AR
• 3-methylglutaconic aciduria type 9 (Supportive), mode of inheritance: AR
• 3-methylglutaconic aciduria type 9 (Moderate), mode of inheritance: AR
• 3-methylglutaconic aciduria type 9 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
3-methylglutaconic aciduria, type IX	AR	Neurologic	The condition can include seizures, and there is a report of specific medical management (with vigabatrin) conferring benefit	Biochemical; Neurologic; Ophthalmologic	27573165; 32369862

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TIMM50 gene.

• not_provided (296 variants)
• Inborn_genetic_diseases (59 variants)
• 3-methylglutaconic_aciduria_type_9 (19 variants)
• TIMM50-related_disorder (4 variants)
• Mitochondrial_encephalopathy (2 variants)
• not_specified (1 variants)
• Mitochondrial_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TIMM50 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001001563.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	91	5	98
missense	3	4	136	5		148
nonsense	1	1	2			4
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)			8			8
Total	4	5	149	96	5

Highest pathogenic variant AF is 0.0000105329555

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TIMM50	protein_coding	protein_coding	ENST00000314349	11	13371

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00178	0.997	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0423	291	293	0.993	0.0000181	2885
Missense in Polyphen		78	95.995	0.81254		943
Synonymous	-1.15	142	126	1.13	0.00000791	968
Loss of Function	2.88	9	24.3	0.370	0.00000119	264

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000531	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane. Has some phosphatase activity in vitro; however such activity may not be relevant in vivo. {ECO:0000269|PubMed:15044455}.
• Disease: DISEASE: 3-methylglutaconic aciduria 9 (MGCA9) [MIM:617698]: An autosomal recessive disease characterized by early-onset seizures, severely delayed psychomotor development and intellectual disability. Patients have hypotonia or spasticity, and laboratory investigations show increased serum lactate and 3-methylglutaconic aciduria. {ECO:0000269|PubMed:27573165}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Metabolism of proteins;Mitochondrial protein import (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.193
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.34

Haploinsufficiency Scores

• pHI: 0.154
• hipred: Y
• hipred_score: 0.588
• ghis: 0.569

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.834

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Timm50
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); vision/eye 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); 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); skeleton phenotype

Gene ontology

• Biological process: release of cytochrome c from mitochondria;protein dephosphorylation;mitochondrial membrane organization;protein import into mitochondrial matrix;peptidyl-tyrosine dephosphorylation
• Cellular component: nucleoplasm;mitochondrion;mitochondrial inner membrane;TIM23 mitochondrial import inner membrane translocase complex;integral component of membrane;nuclear speck
• Molecular function: RNA binding;phosphoprotein phosphatase activity;protein serine/threonine phosphatase activity;protein tyrosine phosphatase activity;interleukin-2 receptor binding;protein binding;ribonucleoprotein complex binding