TIMM8A translocase of inner mitochondrial membrane 8 homolog A (yeast) [Homo sapiens (human)] - Gene

Summary

Go to the top of the page Help

Official Symbol: TIMM8Aprovided by HGNC
Official Full Name: translocase of inner mitochondrial membrane 8 homolog A (yeast)provided by HGNC
Primary source: HGNC:11817
See related: Ensembl:ENSG00000126953; HPRD:02287; MIM:300356; Vega:OTTHUMG00000022028
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DDP; MTS; DDP1; DFN1; TIM8
Summary: This translocase is involved in the import and insertion of hydrophobic membrane proteins from the cytoplasm into the mitochondrial inner membrane. The gene is mutated in Mohr-Tranebjaerg syndrome/Deafness Dystonia Syndrome (MTS/DDS) and it is postulated that MTS/DDS is a mitochondrial disease caused by a defective mitochondrial protein import system. Defects in this gene also cause Jensen syndrome; an X-linked disease with opticoacoustic nerve atrophy and muscle weakness. This protein, along with TIMM13, forms a 70 kDa heterohexamer. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Mar 2009]

Genomic context

Go to the top of the page Help

Location :: Xq22.1

Sequence :: Chromosome: X; NC_000023.10 (100600644..100603957, complement)

See TIMM8A in Epigenomics, MapViewer

Chromosome X - NC_000023.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions What's a GeneRIF?

knockdown of the TIMM8A gene by RNA interference did not show an influence on the oxygen respiration rate and the mitochondrial membrane potentia
Title: Alterations in expression levels of deafness dystonia protein 1 affect mitochondrial morphology.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Observational study of gene-disease association. (HuGE Navigator)
Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
A sporadic 42-year-old man with MTS presenting with postlingual deafness, adult-onset progressive dystonia with marked arm tremor, mild spasticity of the legs, and visual disturbance due to a novel mutation in the DDP1 gene.
Title: Blepharospasm and limb dystonia caused by Mohr-Tranebjaerg syndrome with a novel splice-site mutation in the deafness/dystonia peptide gene.
mRNA expression demonstrate increased TIMM8A mRNA levels in cultured fibroblasts from a patient with Mohr-Tranebjaerg Syndrome.
Title: Molecular genetics of a patient with Mohr-Tranebjaerg Syndrome due to a new mutation in the DDP1 gene.
Bax/Bak-dependent release of DDP/TIMM8a promotes Drp1-mediated mitochondrial fission and mitoptosis during programmed cell death.
Title: Bax/Bak-dependent release of DDP/TIMM8a promotes Drp1-mediated mitochondrial fission and mitoptosis during programmed cell death.
Interaction of TIMM8a with the signal transduction adaptor molecule STAM1.
Title: Interaction of the deafness-dystonia protein DDP/TIMM8a with the signal transduction adaptor molecule STAM1.
Intronic mutations in the DDP1 gene can also cause X-linked dystonia-deafness syndrome.
Title: A novel intronic mutation in the DDP1 gene in a family with X-linked dystonia-deafness syndrome.
Mutation in TIMM8a is associated with deafness-dystonia (Mohr-Tranebjaerg) syndrome
Title: A novel mutation in the gene encoding TIMM8a, a component of the mitochondrial protein translocase complexes, in a Spanish familial case of deafness-dystonia (Mohr-Tranebjaerg) syndrome.

Submit: New GeneRIF Correction

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Males with deafness-dystonia-optic neuronopathy (DDON) syndrome have prelingual or postlingual sensorineural hearing impairment in early childhood, slowly progressive dystonia or ataxia in the teens, slowly progressive decreased visual acuity from optic atrophy beginning approximately age 20 years, and dementia beginning at approximately age 40 years. Psychiatric symptoms such as personality change and paranoia may appear in childhood and progress. The hearing impairment appears to be consistent in age of onset and progression, whereas the neurologic, visual, and neuropsychiatric signs vary in degree of severity and rate of progression. Females may have mild hearing impairment and focal dystonia.

Diagnosis Testing

DDON syndrome occurs as either a single-gene disorder resulting from mutation in TIMM8A or a contiguous gene deletion syndrome at Xq22, which also includes X-linked agammaglobulinemia caused by disruption of BTK, located telomeric to TIMM8A. The diagnosis of DDON syndrome is established by clinical findings. Sequencing of TIMM8A is clinically available.

Genetic Counseling

DDON syndrome is inherited in an X-linked manner. Women who are carriers have a 50% chance of transmitting the TIMM8A mutation in each pregnancy. Males who inherit the mutation will be affected; females who inherit the mutation will be carriers and may have mild hearing loss or focal dystonia at an older age. Thus, with each pregnancy, a woman who is a carrier has a 25% chance of having an affected son. Males who are capable of reproducing pass the disease-causing mutation to all of their daughters and none of their sons. Prenatal testing for pregnancies at increased risk is possible for families in which the disease-causing TIMM8A mutation has been identified.

References

PMID: 20301395

Mohr-Tranebjaerg syndrome

MIM: 304700

Genetic Testing Registry

Summary from GeneReviews: Deafness-Dystonia-Optic Neuronopathy Syndrome

Disease Characteristics

Males with deafness-dystonia-optic neuronopathy (DDON) syndrome have prelingual or postlingual sensorineural hearing impairment in early childhood, slowly progressive dystonia or ataxia in the teens, slowly progressive decreased visual acuity from optic atrophy beginning approximately age 20 years, and dementia beginning at approximately age 40 years. Psychiatric symptoms such as personality change and paranoia may appear in childhood and progress. The hearing impairment appears to be consistent in age of onset and progression, whereas the neurologic, visual, and neuropsychiatric signs vary in degree of severity and rate of progression. Females may have mild hearing impairment and focal dystonia.

Diagnosis Testing

DDON syndrome occurs as either a single-gene disorder resulting from mutation in TIMM8A or a contiguous gene deletion syndrome at Xq22, which also includes X-linked agammaglobulinemia caused by disruption of BTK, located telomeric to TIMM8A. The diagnosis of DDON syndrome is established by clinical findings. Sequencing of TIMM8A is clinically available.

Genetic Counseling

DDON syndrome is inherited in an X-linked manner. Women who are carriers have a 50% chance of transmitting the TIMM8A mutation in each pregnancy. Males who inherit the mutation will be affected; females who inherit the mutation will be carriers and may have mild hearing loss or focal dystonia at an older age. Thus, with each pregnancy, a woman who is a carrier has a 25% chance of having an affected son. Males who are capable of reproducing pass the disease-causing mutation to all of their daughters and none of their sons. Prenatal testing for pregnancies at increased risk is possible for families in which the disease-causing TIMM8A mutation has been identified.

References

PMID: 20301395

HIV-1 protein interactions

Go to the top of the page Help

Protein	Gene	Interaction	Pubs
Envelope transmembrane glycoprotein gp41	env	HIV-1 gp41 is identified to have a physical interaction with translocase of inner mitochondrial membrane 8 homolog A (TIMM8A) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Source	Pubs	Description
O60220	Q92783	STAM	HPRD	PubMed
O60220	Q9Y5L4	TIMM13	HPRD	PubMed
BioGRID:108042	BioGRID:115257	JOSD1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108042	BioGRID:113722	STAM	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:108042	BioGRID:117722	TIMM13	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:108042	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108042	BioGRID:114672	UBE2L6	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108042	BioGRID:124238	USP30	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108042	BioGRID:1205544	env	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

Go to the top of the page Help

Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
Mitochondrial Protein Import, organism-specific biosystem (from REACTOME)
Mitochondrial Protein Import, organism-specific biosystemA human mitochondrion contains about 1500 proteins, more than 99% of which are encoded in the nucleus, synthesized in the cytosol and imported into the mitochondrion. Proteins are targeted to four lo...

General gene information

Go to the top of the page Help

Markers

RH35738 (e-PCR)
- UniSTS:49927

RH93533 (e-PCR)
- UniSTS:84045

D20S1036 (e-PCR)
- UniSTS:12700

G44349 (e-PCR)
- UniSTS:95136

GDB:376892 (e-PCR)
- UniSTS:98978

Genotypes

See TIMM8A SNP Geneview Report
See TIMM8A SNP Genotype Report
See TIMM8A SNP Variation Viewer Report

Related pseudogene(s)

1 found Review record(s) in Gene

Homology

Homologs of the TIMM8A gene: The TIMM8A gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Clone Names

MGC12262

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
metal ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cellular protein metabolic process	TAS Traceable Author Statement more info
chaperone-mediated protein transport	TAS Traceable Author Statement more info	PubMed
nervous system development	TAS Traceable Author Statement more info	PubMed
protein targeting to mitochondrion	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
mitochondrial inner membrane	IEA Inferred from Electronic Annotation more info
mitochondrial intermembrane space	IDA Inferred from Direct Assay more info	PubMed
mitochondrion	IDA Inferred from Direct Assay more info

General protein information

Go to the top of the page Help

Preferred Names: mitochondrial import inner membrane translocase subunit Tim8 A

Names: mitochondrial import inner membrane translocase subunit Tim8 A; deafness/dystonia peptide; deafness dystonia protein 1; X-linked deafness dystonia protein

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011734.1 RefSeqGene

Range

5001..8314

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001145951.1 → NP_001139423.1 mitochondrial import inner membrane translocase subunit Tim8 A isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate exon for its 3' terminus, compared to variant 1, which results in an isoform (2) with a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

BM467820, BQ013177

Conserved Domains (1) summary

pfam02953
Location:20 – 44
Blast Score: 86

zf-Tim10_DDP; Tim10/DDP family zinc finger
NM_004085.3 → NP_004076.1 mitochondrial import inner membrane translocase subunit Tim8 A isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AW204693, BC006994, CN410182

Consensus CDS

CCDS14481.1

UniProtKB/Swiss-Prot

O60220

Related

ENSP00000361993, OTTHUMP00000023681, ENST00000372902, OTTHUMT00000057554

Conserved Domains (1) summary

pfam02953
Location:20 – 83
Blast Score: 200

zf-Tim10_DDP; Tim10/DDP family zinc finger

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 PATCHES

Genomic

NW_004070883.1 Reference GRCh37.p10 PATCHES

Range

27332..30645, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000023.10 Reference GRCh37.p10 Primary Assembly

Range

100600644..100603957, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000155.1 Alternate HuRef

Range

90406792..90410105, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018934.1 Alternate CHM1_1.0

Range

100567642..100570955, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_032696.1: Suppressed sequence

Description

NM_032696.1: This RefSeq was suppressed temporarily based on the calculation that the annotated protein was shorter than a protein or proteins from a putative ortholog.

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01044974.1 (15772..19085)	None
genomic	AL035422.12 (27432..30745)	None
genomic	AMYH01022725.1 (372324..375637)	None
genomic	CH471115.1	EAX02853.1
		EAX02854.1
mRNA	AK312117.1	BAG35053.1
mRNA	AW204693.1	None
mRNA	BC005236.1	None
mRNA	BC006994.1	AAH06994.1
mRNA	BC015093.1	AAH15093.1
mRNA	BC070284.1	AAH70284.1
mRNA	BM467820.1	None
mRNA	BQ013177.1	None
mRNA	CN410182.1	None
mRNA	U66035.1	AAC15946.1