TIMM8B

Chr 11

translocase of inner mitochondrial membrane 8 homolog B

Also known as: DDP2, TIM8B

NCBI Gene: 26521 ENSG00000150779 UniProt: Q9Y5J9 OMIM: 606659

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of a well-conserved family of proteins with similarity to yeast Tim mitochondrial import proteins. This gene is encoded by a nuclear gene and is transported into the intermembrane space of the mitochondrion. When formed into complexes, these proteins guide membrane-spanning proteins across the mitochondrial intermembrane space before they are added into the mitochondrial inner membrane. This gene is adjacent to succinate dehydrogenase, subunit D (SDHD), in which mutations have been found in affected members of families with hereditary paraganglioma.[provided by RefSeq, Aug 2009]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.80

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.80LOEUF

pLI 0.009

Z-score 0.24

OE 0.86 (0.38–1.80)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.58Z-score

OE missense 1.21 (1.00–1.47)

72 obs / 59.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.86 (0.38–1.80)

0≤0.351.4

Missense OE?1.21 (1.00–1.47)

0≤0.61.4

Synonymous OE?1.66

0≤1.21.6

LoF obs/exp: 3 / 3.5Missense obs/exp: 72 / 59.5Syn Z: -2.33

Background carrier burden — how many people carry a rare variant somewhere in TIMM8B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 500

145 rare PASS variants

Rare truncating (LoF)

1 in 1,200

27 rare PASS variants

Rare synonymous (reference)

1 in 480

62 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TIMM8B; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 570	1 in 1,500
South Asian	~43k	1 in 340	1 in 5,300
Remaining (unassigned)	~30k	1 in 640	1 in 1,300
European (Finnish)	~27k	1 in 3,900	1 in 2,100
Admixed American	~22k	1 in 370	1 in 1,500
African / African American	~21k	1 in 350	1 in 880
East Asian	~20k	1 in 430	none seen
Ashkenazi Jewish	~13k	≈ 1 in 6,500	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 360	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓