TAMM41
protein-codingTAM41 mitochondrial translocator assembly and maintenance homolog
Gene summary
Predicted to enable phosphatidate cytidylyltransferase activity. Predicted to be involved in CDP-diacylglycerol biosynthetic process and cardiolipin biosynthetic process. Is active in mitochondrion. Implicated in combined oxidative phosphorylation deficiency 56. [provided by Alliance of Genome Resources, Jul 2025]
- C3orf31
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~56.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0044970
Submitter: ClinGen
The relationship between *TAMM41* and *TAMM41*-related primary mitochondrial disease was evaluated using the ClinGen Clinical Validity Framework as of October 27, 2025. The *TAMM41* gene encodes mitochondrial translocator assembly and maintenance homolog 41, a phosphatidate cytidylyltransferase that is the first mitochondrial enzyme of the cardiolipin biosynthesis pathway, catalyzing the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG). The first and only report of the *TAMM41* gene in relation to autosomal recessive *TAMM41*-related primary mitochondrial disease was in 2022 (PMID: 35321494). *TAMM41* has been associated with a single disease entity to date; combined oxidative phosphorylation deficiency 56 [OMIM# 620139]. This is one disease entity according to the ClinGen Lumping and Splitting Framework, and has been renamed as *TAMM41*-related primary mitochondrial disease. Evidence supporting this gene-disease relationship includes case-level data and experimental data. This curation included six variants identified in three unrelated cases from one publication (PMIDs: 35321494). Clinical features in affected individuals included failure to thrive, global developmental delay, myopathy, chronic progressive external ophthalmoplegia, ptosis, respiratory failure, elevated creatine kinase, and decreased activities of the respiratory chain in skeletal muscle. The mechanism of disease is loss of function. This gene-disease relationship is also supported by a biochemical function shared with other genes associated with primary mitochondrial disease (PMID: 33340416), functional alteration in non-patient cells (PMID: 29253589), and a yeast model (PMID: 35321494). In summary, there is moderate evidence to support the relationship between *TAMM41* and autosomal recessive *TAMM41*-related primary mitochondrial disease. While more evidence is needed to establish this relationship definitively, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on October 27, 2025 (SOP Version 11).
Inheritance Pattern: AR
Disease ID:MONDO:0859323
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0859323
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0859323
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Musculoskeletal; Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TAMM41 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001284401.2. 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 | 3 | 5 | 8 | |||
| missense | 1 | 1 | 51 | 3 | 56 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | |||
| Total | 3 | 1 | 55 | 8 | 0 | 67 |
Highest pathogenic variant AF is 0.000043881093
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001271330.1 | 8 | MANE Select | |
| Ensembl | ENSP00000398596.1 | 8 | MANE Select | |
| RefSeq | NP_001308223.1 | 8 | Standard | |
| RefSeq | NP_001308224.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- CDP-diacylglycerol biosynthetic process
- cardiolipin biosynthetic process
Molecular Function
- phosphatidate cytidylyltransferase activity
- protein binding
Cellular Component
- extrinsic component of mitochondrial inner membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000273037
- Coding exons
- 7
- Length
- 56478
- Individuals with no LoFs
- 125698
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 50
- Defined
- 125748
- p
- 0.000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.00649 | 172 | 172 | 1.00 | 0.00000856 | 2065 |
| Missense (PolyPhen) | 48 | 57.985 | 0.8278 | 701 | ||
| Synonymous | -1.03 | 80 | 69.2 | 1.16 | 0.00000380 | 592 |
| Loss of Function | 1.37 | 12 | 18.3 | 0.654 | 0.00000103 | 194 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00049 | 0.00049 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00054 | 0.00054 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00012 | 0.00012 | rare |
| South Asian | 0.00020 | 0.00016 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the formation of CDP-diacylglycerol (CDP-DAG) from phosphatidic acid (PA) in the mitochondrial inner membrane. Required for the biosynthesis of the dimeric phospholipid cardiolipin, which stabilizes supercomplexes of the mitochondrial respiratory chain in the mitochondrial inner membrane (By similarity). {ECO:0000250}.;
Intolerance Scores
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.54
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- 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 |