PEMT
protein-codingphosphatidylethanolamine N-methyltransferase, the group of Methyltransferase families
Gene summary
Phosphatidylcholine (PC) is the most abundant mammalian phospholipid. This gene encodes an enzyme which converts phosphatidylethanolamine to phosphatidylcholine by sequential methylation in the liver. Another distinct synthetic pathway in nucleated cells converts intracellular choline to phosphatidylcholine by a three-step process. The protein isoforms encoded by this gene localize to the endoplasmic reticulum and mitochondria-associated membranes. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~86.1 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 PEMT variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_148172.3. 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 | 0 | |||||
| missense | 25 | 3 | 1 | 29 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 27 | 3 | 1 | 31 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_680477.1 | 7 | MANE Select | |
| Ensembl | ENSP00000255389.5 | 7 | MANE Select | |
| RefSeq | NP_001254480.1 | 7 | Standard | |
| RefSeq | NP_001254481.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycerophospholipid metabolism - Homo sapiens (human)
- Betaine Metabolism
- Phospholipid Biosynthesis
- Kennedy pathway from Sphingolipids
- One carbon metabolism and related pathways
Biological Process
- blastocyst hatching
- lipid metabolic process
- phosphatidylcholine biosynthetic process
- sphingomyelin biosynthetic process
- cell population proliferation
Molecular Function
- phosphatidyl-N-methylethanolamine N-methyltransferase activity
- phosphatidylethanolamine N-methyltransferase activity
- phosphatidylethanolamine binding
- phosphatidyl-N-dimethylethanolamine N-methyltransferase activity
Cellular Component
- endoplasmic reticulum membrane
- integral component of membrane
- brush border membrane
- mitochondrial membrane
- sarcolemma
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000255389
- Coding exons
- 7
- Length
- 86146
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125747
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.112 | 142 | 138 | 1.03 | 0.00000842 | 1492 |
| Missense (PolyPhen) | 35 | 40.624 | 0.86155 | 492 | ||
| Synonymous | -0.189 | 68 | 66.0 | 1.03 | 0.00000452 | 495 |
| Loss of Function | 2.35 | 3 | 11.6 | 0.258 | 5.95e-7 | 123 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the three sequential steps of the methylation pathway of phosphatidylcholine biosynthesis, the SAM-dependent methylation of phosphatidylethanolamine (PE) to phosphatidylmonomethylethanolamine (PMME), PMME to phosphatidyldimethylethanolamine (PDME), and PDME to phosphatidylcholine (PC). {ECO:0000255|HAMAP-Rule:MF_03216}.;
Recessive Scores
- pRec
- 0.217
Intolerance Scores
- LoFtool
- 0.457
- RVIS EVS
- 0.84
- RVIS percentile EVS
- 88.3
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.467
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |