TIMM21
protein-codingtranslocase of inner mitochondrial membrane 21, the group of TIM23 complex
Gene summary
Involved in mitochondrial respiratory chain complex I assembly; mitochondrial respiratory chain complex IV assembly; and protein import into mitochondrial matrix. Located in mitochondrion. Part of TIM23 mitochondrial import inner membrane translocase complex. [provided by Alliance of Genome Resources, Jun 2026]
- C18orf55
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.0 kbGenCC 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 TIMM21 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014177.3. 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 | 1 | 1 | ||||
| missense | 47 | 4 | 51 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 48 | 4 | 0 | 52 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_054896.2 | 6 | MANE Select | |
| Ensembl | ENSP00000169551.6 | 6 | MANE Select | |
| Ensembl | ENSP00000464228.1 | 4 | Standard | |
| Ensembl | ENSP00000462028.1 | 4 | 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 import into mitochondrial matrix
- mitochondrial respiratory chain complex I assembly
- mitochondrial respiratory chain complex IV assembly
Molecular Function
- molecular_function
- protein binding
Cellular Component
- TIM23 mitochondrial import inner membrane translocase complex
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000169551
- Coding exons
- 6
- Length
- 10452
- Individuals with no LoFs
- 125720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 28
- Defined
- 125748
- p
- 0.000111
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.00783 | 136 | 136 | 0.998 | 0.00000715 | 1588 |
| Missense (PolyPhen) | 34 | 39.896 | 0.85221 | 419 | ||
| Synonymous | -0.0638 | 54 | 53.4 | 1.01 | 0.00000286 | 485 |
| Loss of Function | 1.20 | 8 | 12.6 | 0.635 | 5.57e-7 | 161 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.00014 | 0.00012 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Participates in the translocation of transit peptide- containing proteins across the mitochondrial inner membrane. Also required for assembly of mitochondrial respiratory chain complex I and complex IV as component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex. Probably shuttles between the presequence translocase and respiratory-chain assembly intermediates in a process that promotes incorporation of early nuclear-encoded subunits into these complexes. {ECO:0000269|PubMed:23260140}.;
Intolerance Scores
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |