TIMM50

Chr 19AR

translocase of inner mitochondrial membrane 50

NCBI Gene: 92609ENSG00000105197UniProt: Q3ZCQ8

Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane (PubMed:30190335, PubMed:38828998). Has some phosphatase activity in vitro; however such activity may not be relevant in vivo

Primary Disease Associations & Inheritance

3-methylglutaconic aciduria, type IXMIM #617698
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TIMM50
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Gene-Disease Validity (ClinGen)
3-methylglutaconic aciduria type 9 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.65LOEUF
pLI 0.002
Z-score 2.88
OE 0.37 (0.22–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.04Z-score
OE missense 0.99 (0.90–1.09)
291 obs / 293.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.37 (0.22–0.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.90–1.09)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.13
0≤1.21.6
LoF obs/exp: 9 / 24.3Missense obs/exp: 291 / 293.0Syn Z: -1.15

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TIMM50 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

3-methylglutaconic aciduria, type IX

MIM #617698

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Biochemical and neurophysiological effects of deficiency of the mitochondrial import protein TIMM50.
Paz E et al.·Elife
2024
Mitochondrial Protein Homeostasis and Cardiomyopathy.
Wachoski-Dark E et al.·Int J Mol Sci
2022Review
Mutations in TIMM50 compromise cell survival in OxPhos-dependent metabolic conditions.
Reyes A et al.·EMBO Mol Med
2018
Reduced Protein Import via TIM23 SORT Drives Disease Pathology in TIMM50-Associated Mitochondrial Disease.
Crameri JJ et al.·Mol Cell Biol
2024Case report
Lactate metabolism-related genes to predict the clinical outcome and molecular characteristics of endometrial cancer.
Shi R et al.·BMC Cancer
2023
Novel variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability in Iranian consanguineous families.
Moudi M et al.·J Clin Lab Anal
2022Case report
MiR-7 mediates mitochondrial impairment to trigger apoptosis and necroptosis in Rhabdomyosarcoma.
Yang L et al.·Biochim Biophys Acta Mol Cell Res
2020
Hotspots for Disease-Causing Mutations in the Mitochondrial TIM23 Import Complex.
Jain S et al.·Genes (Basel)
2024Review
HTRA2 Defect: A Recognizable Inborn Error of Metabolism with 3-Methylglutaconic Aciduria as Discriminating Feature Characterized by Neonatal Movement Disorder and Epilepsy-Report of 11 Patients.
Kovacs-Nagy R et al.·Neuropediatrics
2018Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools