TIMM8A |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- TIMM8A (HGNC:11817) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- translocase of inner mitochondrial membrane 8A
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- DFN1
- Alias symbols
- DDP, MTS
- %HI
- 16.93(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.65(Read more about gnomAD pLI score)
- LOEUF
- 0.87(Read more about gnomAD LOEUF score)
- Cytoband
- Xq22.1
- Genomic Coordinates
-
GRCh37/hg19: chrX:100600649-100603730 NCBI Ensembl UCSC GRCh38/hg38: chrX:101345661-101348742 NCBI Ensembl UCSC - MANE Select Transcript
- NM_004085.4 ENST00000372902.4 (Read more about MANE Select)
- 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 med... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- deafness dystonia syndrome Monarch
-
PUBMED:
11405816
Ujike et al (2001) identified a nonsense variant of TIMM8A in a family with multiple affected males with X-linked dystonia-deafness syndrome (Mohr-Tranebjaerg syndrome; MTS).
-
PUBMED:
17471106
Bahmad Jr. et al (2007) reported a frameshift variant in TIMM8A in 16 affected males from a large, multigeneration, Norwegian family with MTS.
-
PUBMED:
22736418
Ha et al (2012) reported six MTS patients from three Australian families. The affected members had exon 2 deletion (Family A), a single base pair deletion resulting in frameshift (Family B), and a nonsense variant (Family 3) of TIMM8A.
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PUBMED:
17851739
Sediva et al (2007) reported several male patients with contiguous X-chromosome deletions encompassing the BTK and TIMM8A genes, resulting in the combination of X-linked agammaglobulinemia (XLA) (associated with loss of the BTK gene) and with sensorineural deafness.
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PUBMED:
30634948
Wang et al (2019) identified a novel frameshift variant (p.Leu78SerfsX21) of TIMM8A in a Chinese family with auditory neuropathy using next generation sequencing. In addition, another patient had an inframe variant (c.133_135delGAG). The third patient showed a deletion involving TIMM8A and BTK genes.
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PUBMED:
31903733
Neighbors et al (2020) reported a novel TIMM8A variant in a patient with MTS (also called deafness-dystonia-optic neuronopathy (DDON) syndrome) that alters the initiation codon (c.1A>T, p.Met1Leu). Functional analysis showed that this variant resulted in no detectable protein and a reduction in TIMM8A transcript abundance. Mother was found to be a carrier, with low copy numbers of the variant compared to wild type, suggesting that mother may be a mosaic for this variant.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.