TIMM8B

protein-coding

translocase of inner mitochondrial membrane 8 homolog B

Gene summary

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]

MANE transcript

NM_012459.4

Inheritance

—

ClinVar variants

U:20

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr11:112,084,800-112,086,798

External References & Databases

Ensembl (ENSG00000150779)

Transcript & Mutation Effects

hg38 • Region Span ~2.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TIMM8B variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 20

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012459.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			18 clinvar			18
nonsense						0
start loss			2 clinvar			2
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	20	0	0	20

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012459.4	RefSeq	NP_036591.3	2	MANE Select
ENST00000504148.3	Ensembl	ENSP00000422122.2	2	MANE Select
ENST00000509359.6	Ensembl	ENSP00000421964.2	2	Standard
ENST00000541231.1	Ensembl	ENSP00000438455.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of proteins
Mitochondrial protein import

Biological Process

protein targeting to mitochondrion
sensory perception of sound
chaperone-mediated protein transport

Molecular Function

zinc ion binding

Cellular Component

extracellular space
mitochondrial inner membrane
mitochondrial intermembrane space protein transporter complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000541231
Coding exons: 2
Length: 1999
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125747
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.578	72	59.5	1.21	0.00000317	637
Missense (PolyPhen)		7	8.6103	0.81298		131
Synonymous	-2.33	34	20.5	1.66	9.01e-7	184
Loss of Function	0.242	3	3.49	0.860	1.47e-7	41

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00033	0.00031	rare
Latino/Admixed American	0.000088	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00016	0.00014	rare
European (Non-Finnish)	0.00028	0.00026	rare
South Asian	0.000067	0.000065	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.145

Intolerance Scores

LoFtool: 0.612
RVIS EVS: -0.14
RVIS percentile EVS: 42.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium