TIMM50

Chr 19

translocase of inner mitochondrial membrane 50

Also known as: MGCA9, TIM50, TIM50L

NCBI Gene: 92609 ENSG00000105197 UniProt: Q3ZCQ8

This protein is an essential component of the TIM23 complex that translocates proteins across the mitochondrial inner membrane by recognizing mitochondrial targeting signals on incoming proteins. Mutations cause 3-methylglutaconic aciduria type IX with autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.646), consistent with mitochondrial dysfunction when both copies are disrupted.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a subunit of the TIM23 inner mitochondrial membrane translocase complex. The encoded protein functions as the receptor subunit that recognizes the mitochondrial targeting signal, or presequence, on protein cargo that is destined for the mitochondrial inner membrane and matrix. This protein may also play a role in maintaining the membrane permeability barrier, and knockdown of this gene in human cells results in the release of cytochrome c and apoptosis. [provided by RefSeq, Jul 2016]

ResearchGenerating clinical summary…

LOEUF 0.65

Clinical Summary— TIMM50

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Gene-Disease Validity (ClinGen)

3-methylglutaconic aciduria type 9 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

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

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 215 VUS of 487 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.002

Z-score 2.88

OE 0.37 (0.22–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.04Z-score

OE missense 0.99 (0.90–1.09)

291 obs / 293.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.22–0.65)

0≤0.351.4

Missense OE?0.99 (0.90–1.09)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 9 / 24.3Missense obs/exp: 291 / 293.0Syn Z: -1.15

ClinVar Variant Classifications

487 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic2

VUS215

Likely Benign221

Benign24

Conflicting6

Pathogenic

Likely Pathogenic

215

VUS

221

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	3	0	0	4
Likely Pathogenic	1	1	0	0	2
VUS	5	138	71	1	215
Likely Benign	0	7	123	91	221
Benign	0	0	19	5	24
Conflicting	—				6
Total	7	149	213	97	472

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap TIMM50 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →