TIMM17B

Chr X

translocase of inner mitochondrial membrane 17B

Also known as: DXS9822, JM3, TIM17B

NCBI Gene: 10245ENSG00000126768UniProt: O60830OMIM: 300249

The protein is an essential component of the TIM23 complex that translocates proteins across the mitochondrial inner membrane into the mitochondrion. Mutations cause autosomal recessive dilated cardiomyopathy with ataxia, a disorder affecting the heart and nervous system. The gene shows relatively low constraint to loss-of-function variation.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.91
Clinical Summary— TIMM17B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.09) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
61 unique Pathogenic / Likely Pathogenic· 29 VUS of 116 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.91LOEUF
pLI 0.085
Z-score 1.76
OE 0.35 (0.16–0.91)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.31Z-score
OE missense 0.61 (0.49–0.76)
55 obs / 90.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.35 (0.16–0.91)
0≤0.351.4
Missense OE0.61 (0.49–0.76)
0≤0.61.4
Synonymous OE0.87
0≤1.21.6
LoF obs/exp: 3 / 8.6Missense obs/exp: 55 / 90.1Syn Z: 0.58
DN
0.81top 10%
GOF
0.72top 25%
LOF
0.3745th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

116 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic59
Likely Pathogenic2
VUS29
Likely Benign4
Benign1
59
Pathogenic
2
Likely Pathogenic
29
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
59
0
59
Likely Pathogenic
0
0
2
0
2
VUS
0
20
9
0
29
Likely Benign
0
1
1
2
4
Benign
0
0
1
0
1
Total02172295

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

View in ClinVar →

Protein Context — Lollipop Plot

TIMM17B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients