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

Summary

Official Symbol: TIMM8Aprovided by HGNC
Official Full Name: translocase of inner mitochondrial membrane 8Aprovided by HGNC
Primary source: HGNC:HGNC:11817
See related: Ensembl:ENSG00000126953 MIM:300356; AllianceGenome:HGNC:11817
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]
Expression: Ubiquitous expression in liver (RPKM 4.3), kidney (RPKM 2.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xq22.1

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (101345661..101348742, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (99789782..99792863, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (100600649..100603730, complement)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Frameshift mutation of Timm8a1 gene in mouse leads to an abnormal mitochondrial structure in the brain, correlating with hearing and memory impairment.
Title: Frameshift mutation of Timm8a1 gene in mouse leads to an abnormal mitochondrial structure in the brain, correlating with hearing and memory impairment.
The authors show that human Tim8a is required for the assembly of Complex IV in neurons, which is mediated through a transient interaction with Complex IV assembly factors, in particular the copper chaperone COX17.
Title: Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying Mohr-Tranebjærg syndrome.
The results of this study demonistrated that the syndrome of deafness-dystonia is cause by mutation of Timm8a.
Title: The syndrome of deafness-dystonia: clinical and genetic heterogeneity.
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.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Deafness dystonia syndrome MedGen: C0796074 OMIM: 304700 GeneReviews: Deafness-Dystonia-Optic Neuronopathy Syndrome	Compare labs

Copy number response

Description
Copy number response Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2021-03-24) ClinGen Genome Curation PagePubMed Triplosensitivity No evidence available (Last evaluated 2021-03-24) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of translocase of inner mitochondrial membrane 8 homolog A (TIMM8A) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells	PubMed

Protein interactions

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

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in nervous system development	TAS Traceable Author Statement more info	PubMed
involved_in protein insertion into mitochondrial inner membrane	NAS Non-traceable Author Statement more info	PubMed
involved_in protein insertion into mitochondrial inner membrane	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in mitochondrial inner membrane	IEA Inferred from Electronic Annotation more info
located_in mitochondrial intermembrane space	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial intermembrane space	NAS Non-traceable Author Statement more info	PubMed
part_of mitochondrial intermembrane space protein transporter complex	IPI Inferred from Physical Interaction more info	PubMed
located_in mitochondrion	HDA more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: mitochondrial import inner membrane translocase subunit Tim8 A

Names: X-linked deafness dystonia protein; deafness dystonia protein 1; deafness/dystonia peptide; translocase of inner mitochondrial membrane 8 homolog A

NCBI Reference Sequences (RefSeq)

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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

5228..8309

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

See identical proteins and their annotated locations for NP_001139423.1

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)

AL035422, BM467820, BQ013177

Consensus CDS

CCDS87768.1

UniProtKB/TrEMBL

A0A2R8YDA8

Related

ENSP00000494385.1, ENST00000644112.2

Conserved Domains (1) summary

pfam02953
Location:21 → 44

zf-Tim10_DDP; Tim10/DDP family zinc finger
NM_004085.4 → NP_004076.1 mitochondrial import inner membrane translocase subunit Tim8 A isoform 1

See identical proteins and their annotated locations for NP_004076.1

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

B2R5A6, O60220, Q6IRW6

Related

ENSP00000361993.3, ENST00000372902.4

Conserved Domains (1) summary

pfam02953
Location:21 → 81

zf-Tim10_DDP; Tim10/DDP family zinc finger

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000023.11 Reference GRCh38.p14 Primary Assembly

Range

101345661..101348742 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060947.1 Alternate T2T-CHM13v2.0

Range

99789782..99792863 complement

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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.