Human Gene TIMM8A (ENST00000372902.4) Description and Page Index
  Description: Homo sapiens translocase of inner mitochondrial membrane 8A (TIMM8A), transcript variant 1, mRNA. (from RefSeq NM_004085)
RefSeq Summary (NM_004085): 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].
Gencode Transcript: ENST00000372902.4
Gencode Gene: ENSG00000126953.8
Transcript (Including UTRs)
   Position: hg38 chrX:101,345,661-101,348,742 Size: 3,082 Total Exon Count: 2 Strand: -
Coding Region
   Position: hg38 chrX:101,346,499-101,348,664 Size: 2,166 Coding Exon Count: 2 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesGeneReviewsMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
Genomic Sequence (chrX:101,345,661-101,348,742)mRNA (may differ from genome)Protein (97 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
ReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Mitochondrial import inner membrane translocase subunit Tim8 A; AltName: Full=Deafness dystonia protein 1; AltName: Full=X-linked deafness dystonia protein;
FUNCTION: 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. The TIMM8-TIMM13 complex mediates the import of proteins such as TIMM23, SLC25A12/ARALAR1 and SLC25A13/ARALAR2, while the predominant TIMM9-TIMM10 70 kDa complex mediates the import of much more proteins. Probably necessary for normal neurologic development.
SUBUNIT: Heterohexamer; composed of 3 copies of TIMM8A and 3 copies of TIMM13, named soluble 70 kDa complex. Associates with the TIM22 complex, whose core is composed of TIMM22.
SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane protein; Intermembrane side.
TISSUE SPECIFICITY: Highly expressed in fetal and adult brain, followed by fetal lung, liver and kidney. Also expressed in heart, placenta, lung, liver, kidney, pancreas, skeletal muscle and heart.
DOMAIN: The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM8A from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity).
DISEASE: Defects in TIMM8A are the cause of Mohr-Tranebjaerg syndrome (MTS) [MIM:304700]; also known as dystonia-deafness syndrome (DDS) or X-linked progressive deafness type 1 (DFN-1). It is a recessive neurodegenerative syndrome characterized by postlingual progressive sensorineural deafness as the first presenting symptom in early childhood, followed by progressive dystonia, spasticity, dysphagia, mental deterioration, paranoia and cortical blindness.
DISEASE: Defects in TIMM8A are the cause of Jensen syndrome (JENSS) [MIM:311150]; also known as opticoacoustic nerve atrophy with dementia. This X-linked disease is characterized by deafness, blindness and muscle weakness.
SIMILARITY: Belongs to the small Tim family.
WEB RESOURCE: Name=GeneReviews; URL="";

-  MalaCards Disease Associations
  MalaCards Gene Search: TIMM8A
Diseases sorted by gene-association score: mohr-tranebjaerg syndrome* (1380), focal dystonia (18), cortical blindness (17), dystonia (17), visual cortex disease (8), visual pathway disease (8), blepharospasm (8), x-linked disease (6), mitochondrial metabolism disease (5), 3-methylglutaconic aciduria, type iii (5), mitochondrial disorders (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 5.38 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 83.86 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -24.2078-0.310 Picture PostScript Text
3' UTR -220.70838-0.263 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR004217 - Tim8/9/10/13_Znf-like

Pfam Domains:
PF02953 - Tim10/DDP family zinc finger

ModBase Predicted Comparative 3D Structure on O60220
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologGenome BrowserGenome Browser
Gene Details    Gene Details
Gene Sorter    Gene Sorter
MGI Ensembl WormBaseSGD
Protein SequenceProtein Sequence  Protein SequenceProtein Sequence
AlignmentAlignment  AlignmentAlignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0046872 metal ion binding

Biological Process:
GO:0007399 nervous system development
GO:0015031 protein transport
GO:0072321 chaperone-mediated protein transport

Cellular Component:
GO:0005739 mitochondrion
GO:0005743 mitochondrial inner membrane
GO:0005758 mitochondrial intermembrane space
GO:0016020 membrane

-  Descriptions from all associated GenBank mRNAs
  BC005236 - Homo sapiens translocase of inner mitochondrial membrane 8 homolog A (yeast), mRNA (cDNA clone IMAGE:3682832).
LF211653 - JP 2014500723-A/19156: Polycomb-Associated Non-Coding RNAs.
MA447230 - JP 2018138019-A/19156: Polycomb-Associated Non-Coding RNAs.
BC070284 - Homo sapiens translocase of inner mitochondrial membrane 8 homolog A (yeast), mRNA (cDNA clone MGC:88277 IMAGE:4281013), complete cds.
BC006994 - Homo sapiens translocase of inner mitochondrial membrane 8 homolog A (yeast), mRNA (cDNA clone MGC:12263 IMAGE:4051368), complete cds.
LF208699 - JP 2014500723-A/16202: Polycomb-Associated Non-Coding RNAs.
MA444276 - JP 2018138019-A/16202: Polycomb-Associated Non-Coding RNAs.
U66035 - Human X-linked deafness dystonia protein (DDP) mRNA, complete cds.
BC015093 - Homo sapiens translocase of inner mitochondrial membrane 8 homolog A (yeast), mRNA (cDNA clone MGC:22690 IMAGE:3684305), complete cds.
JD196759 - Sequence 177783 from Patent EP1572962.
LF382209 - JP 2014500723-A/189712: Polycomb-Associated Non-Coding RNAs.
MA617786 - JP 2018138019-A/189712: Polycomb-Associated Non-Coding RNAs.
LF321701 - JP 2014500723-A/129204: Polycomb-Associated Non-Coding RNAs.
MA557278 - JP 2018138019-A/129204: Polycomb-Associated Non-Coding RNAs.
LF382210 - JP 2014500723-A/189713: Polycomb-Associated Non-Coding RNAs.
MA617787 - JP 2018138019-A/189713: Polycomb-Associated Non-Coding RNAs.
LF321700 - JP 2014500723-A/129203: Polycomb-Associated Non-Coding RNAs.
MA557277 - JP 2018138019-A/129203: Polycomb-Associated Non-Coding RNAs.
JD510411 - Sequence 491435 from Patent EP1572962.
JD084452 - Sequence 65476 from Patent EP1572962.
JD235350 - Sequence 216374 from Patent EP1572962.
JD550845 - Sequence 531869 from Patent EP1572962.
JD215742 - Sequence 196766 from Patent EP1572962.
LF382212 - JP 2014500723-A/189715: Polycomb-Associated Non-Coding RNAs.
MA617789 - JP 2018138019-A/189715: Polycomb-Associated Non-Coding RNAs.
LF321698 - JP 2014500723-A/129201: Polycomb-Associated Non-Coding RNAs.
MA557275 - JP 2018138019-A/129201: Polycomb-Associated Non-Coding RNAs.
JD082160 - Sequence 63184 from Patent EP1572962.
JD490530 - Sequence 471554 from Patent EP1572962.
JD022463 - Sequence 3487 from Patent EP1572962.
LF382213 - JP 2014500723-A/189716: Polycomb-Associated Non-Coding RNAs.
MA617790 - JP 2018138019-A/189716: Polycomb-Associated Non-Coding RNAs.
DQ591338 - Homo sapiens piRNA piR-58450, complete sequence.
LF382214 - JP 2014500723-A/189717: Polycomb-Associated Non-Coding RNAs.
MA617791 - JP 2018138019-A/189717: Polycomb-Associated Non-Coding RNAs.
LF321697 - JP 2014500723-A/129200: Polycomb-Associated Non-Coding RNAs.
MA557274 - JP 2018138019-A/129200: Polycomb-Associated Non-Coding RNAs.
JD486660 - Sequence 467684 from Patent EP1572962.
LF382216 - JP 2014500723-A/189719: Polycomb-Associated Non-Coding RNAs.
MA617793 - JP 2018138019-A/189719: Polycomb-Associated Non-Coding RNAs.
LF321696 - JP 2014500723-A/129199: Polycomb-Associated Non-Coding RNAs.
MA557273 - JP 2018138019-A/129199: Polycomb-Associated Non-Coding RNAs.
JD524569 - Sequence 505593 from Patent EP1572962.
AK312117 - Homo sapiens cDNA, FLJ92399, Homo sapiens translocase of inner mitochondrial membrane 8 homologA (yeast) (TIMM8A), nuclear gene encoding mitochondrial protein,mRNA.
JD310076 - Sequence 291100 from Patent EP1572962.
KJ891045 - Synthetic construct Homo sapiens clone ccsbBroadEn_00439 TIMM8A gene, encodes complete protein.
KR710181 - Synthetic construct Homo sapiens clone CCSBHm_00010237 TIMM8A (TIMM8A) mRNA, encodes complete protein.
LF321694 - JP 2014500723-A/129197: Polycomb-Associated Non-Coding RNAs.
MA557271 - JP 2018138019-A/129197: Polycomb-Associated Non-Coding RNAs.
LF385349 - JP 2014500723-A/192852: Polycomb-Associated Non-Coding RNAs.
MA620926 - JP 2018138019-A/192852: Polycomb-Associated Non-Coding RNAs.
JD407061 - Sequence 388085 from Patent EP1572962.
JD398232 - Sequence 379256 from Patent EP1572962.
JD254029 - Sequence 235053 from Patent EP1572962.
JD274323 - Sequence 255347 from Patent EP1572962.
JD207287 - Sequence 188311 from Patent EP1572962.
JD257563 - Sequence 238587 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O60220 (Reactome details) participates in the following event(s):

R-HSA-1307802 MIA40:ERV1 (CHCHD4:GFER) oxidizes cysteine residues to cystine disulfide bonds
R-HSA-1299484 TIMM8:TIMM13 chaperones hydrophobic proteins
R-HSA-1268020 Mitochondrial protein import
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: B2R5A6, DDP, DDP1, NM_004085, O60220, Q6IRW6, TIM8A, TIM8A_HUMAN, uc004ehd.1, uc004ehd.2, uc004ehd.3, uc004ehd.4
UCSC ID: uc004ehd.4
RefSeq Accession: NM_004085
Protein: O60220 (aka TIM8A_HUMAN)
CCDS: CCDS14481.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene TIMM8A:
ddon (Deafness-Dystonia-Optic Neuronopathy Syndrome)
dystonia-ov (Hereditary Dystonia Overview)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.