PCMT1
protein-codingprotein-L-isoaspartate (D-aspartate) O-methyltransferase, the group of 7BS protein methyltransferases
Gene summary
This gene encodes a member of the type II class of protein carboxyl methyltransferase enzymes. The encoded enzyme plays a role in protein repair by recognizing and converting D-aspartyl and L-isoaspartyl residues resulting from spontaneous deamidation back to the normal L-aspartyl form. The encoded protein may play a protective role in the pathogenesis of Alzheimer's disease, and single nucleotide polymorphisms in this gene have been associated with spina bifida and premature ovarian failure. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~62.0 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 PCMT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001360452.2. 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 | 1 | 1 | 2 | |||
| missense | 15 | 15 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 16 | 1 | 0 | 17 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001347381.1 | 7 | MANE Select | |
| Ensembl | ENSP00000420813.2 | 7 | MANE Select | |
| RefSeq | NP_001238978.1 | 8 | Standard | |
| RefSeq | NP_001238979.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of proteins
- Protein repair
Biological Process
- protein methylation
- protein repair
Molecular Function
- protein-L-isoaspartate (D-aspartate) O-methyltransferase activity
- protein binding
- cadherin binding
Cellular Component
- cytoplasm
- cytosol
- extracellular exosome
- extracellular vesicle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367384
- Coding exons
- 8
- Length
- 61978
- Individuals with no LoFs
- 119988
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 119989
- p
- 0.00000417
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.90 | 91 | 158 | 0.575 | 0.00000776 | 1834 |
| Missense (PolyPhen) | 9 | 51.428 | 0.175 | 603 | ||
| Synonymous | -0.0199 | 62 | 61.8 | 1.00 | 0.00000319 | 569 |
| Loss of Function | 2.95 | 2 | 13.8 | 0.145 | 5.88e-7 | 180 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000030 | 0.000030 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the methyl esterification of L-isoaspartyl and D-aspartyl residues in peptides and proteins that result from spontaneous decomposition of normal L-aspartyl and L-asparaginyl residues. It plays a role in the repair and/or degradation of damaged proteins. Acts on EIF4EBP2, microtubule-associated protein 2, calreticulin, clathrin light chains a and b, Ubiquitin carboxyl-terminal hydrolase isozyme L1, phosphatidylethanolamine- binding protein 1, stathmin, beta-synuclein and alpha-synuclein. {ECO:0000250|UniProtKB:P23506}.;
Recessive Scores
- pRec
- 0.177
Intolerance Scores
- LoFtool
- 0.298
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 2.22e-16
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |