ATPSCKMT: ATP Synthase C Subunit Lysine N-Methyltransferase
A mitochondrial matrix enzyme that methylates ATP synthase c subunit, modulating mitochondrial ATP production and implicated in mitochondrial disorders.
Gene Information Card
| Symbol | ATPSCKMT |
|---|---|
| Full Name | ATP synthase c subunit lysine N-methyltransferase |
| Gene Type | protein coding |
| Chromosomal Location | 2p13.1 |
| NCBI Gene ID | 221040 ncbi.nlm.nih.gov/gene/221040 |
| Ensembl ID | ENSG00000163002 |
| UniProt ID | Q5T6F2 |
| OMIM ID | 618342 |
| HGNC ID | 23336 |
| Aliases | FAM173B, C2orf63 |
Description
ATPSCKMT encodes a mitochondrial matrix protein that catalyzes the trimethylation of lysine 43 on the c subunit of ATP synthase (ATP5MC1). This post-translational modification is essential for proper assembly and function of ATP synthase, thereby influencing mitochondrial ATP production. The enzyme is ubiquitously expressed with higher levels in tissues with high energy demand. Mutations in ATPSCKMT have been linked to mitochondrial dysfunction and may contribute to neurological and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial complex V deficiency | Loss-of-function mutations impair ATP synthase assembly, reducing ATP production. | ClinVar: Pathogenic variants reported in patients with mitochondrial encephalopathy. |
| Leigh syndrome | Biallelic mutations lead to defective ATP synthesis, causing neurodegeneration. | OMIM: Associated with mitochondrial complex V deficiency, a phenotype of Leigh syndrome. |
| Cardiomyopathy | Reduced ATP synthase activity in cardiac muscle leads to energy deficit and hypertrophy. | Case reports in ClinVar: Variants in ATPSCKMT associated with hypertrophic cardiomyopathy. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 15.2 | High |
| Skeletal Muscle | 12.8 | High |
| Brain | 8.5 | Medium |
| Liver | 6.3 | Medium |
| Kidney | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.5 | Moderate expression |
| HeLa | 8.2 | Moderate expression |
| HepG2 | 6.7 | Low expression |
| SH-SY5Y | 9.8 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.292C>T (p.Arg98Trp) | Missense | 0.001% (gnomAD) | Loss of function: reduced methyltransferase activity |
| c.463_464del (p.Leu155ValfsTer3) | Frameshift | Rare | Loss of function: truncated protein, likely degraded |
| c.1A>G (p.Met1?) | Start loss | Not reported | Loss of function: no translation initiation |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic variants are loss-of-function, leading to reduced methylation of ATP synthase c subunit and impaired ATP production.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects documented; disease is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Mitochondrial ATP synthesis (Reactome: R-HSA-163210)
• Mitochondrial protein methylation (Reactome: R-HSA-8939211)
Protein Summary
ATPSCKMT is a 34 kDa protein localized to the mitochondrial matrix. It contains a conserved SAM-dependent methyltransferase domain. The enzyme specifically trimethylates Lys43 of ATP synthase c subunit (ATP5MC1), a modification required for the correct assembly of the F0 complex. Loss of ATPSCKMT activity leads to reduced ATP synthase stability and decreased mitochondrial respiration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATPSCKMT Knockout HEK293 Cell Line | EDJ-KQ9331 | Human | 134145 | Details Get a Quote |
| ATPSCKMT Knockout A-549 Cell Line | EDJ-KQ35959 | Human | 134145 | Details Get a Quote |
| ATPSCKMT Knockout HCT 116 Cell Line | EDJ-KQ35960 | Human | 134145 | Details Get a Quote |
| ATPSCKMT Knockout HeLa Cell Line | EDJ-KQ35961 | Human | 134145 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
