TIMM8B

Chr 11

translocase of inner mitochondrial membrane 8 homolog B

Also known as: DDP2, TIM8B

TIMM8B encodes a mitochondrial intermembrane chaperone that guides membrane-spanning proteins through the intermembrane space and facilitates their insertion into the mitochondrial inner membrane. The gene shows low constraint to loss-of-function variation (pLI 0.009, LOEUF 1.80), and no established human disease associations have been reported to date. TIMM8B is located adjacent to SDHD, a gene associated with hereditary paraganglioma.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.80
Clinical SummaryTIMM8B
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.80LOEUF
pLI 0.009
Z-score 0.24
OE 0.86 (0.381.80)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.58Z-score
OE missense 1.21 (1.001.47)
72 obs / 59.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.86 (0.381.80)
00.351.4
Missense OE1.21 (1.001.47)
00.61.4
Synonymous OE1.66
01.21.6
LoF obs/exp: 3 / 3.5Missense obs/exp: 72 / 59.5Syn Z: -2.33
DN
0.78top 25%
GOF
0.75top 25%
LOF
0.1895th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TIMM8B · 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

No active trials found for this gene.

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Clinical Literature
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