METTL27
protein-codingmethyltransferase like 27, the group of 7BS orphan methyltransferases
Gene summary
This gene encodes a protein belonging to ubiE/COQ5 methyltransferase family. The gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.22-q11.23. [provided by RefSeq, Jul 2008]
- WBSCR27
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.9 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 METTL27 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152559.3. 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 | 5 | 5 | ||||
| missense | 37 | 4 | 41 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | |||
| Total | 0 | 0 | 38 | 10 | 0 | 48 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689772.2 | 5 | MANE Select | |
| Ensembl | ENSP00000297873.4 | 5 | MANE Select | |
| Ensembl | ENSP00000398533.1 | 3 | Standard | |
| Ensembl | ENSP00000536896.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Molecular Function
- protein binding
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000297873
- Coding exons
- 5
- Length
- 7946
- Individuals with no LoFs
- 124767
- Homozygous LoFs
- 50
- Heterozygous LoFs
- 915
- Defined
- 125732
- p
- 0.00384
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.456 | 161 | 146 | 1.11 | 0.00000862 | 1531 |
| Missense (PolyPhen) | 37 | 30.699 | 1.2053 | 379 | ||
| Synonymous | -0.956 | 79 | 68.9 | 1.15 | 0.00000461 | 533 |
| Loss of Function | 1.55 | 3 | 7.60 | 0.395 | 3.25e-7 | 87 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0025 | 0.0022 | notable |
| Latino/Admixed American | 0.0026 | 0.0021 | notable |
| Ashkenazi Jewish | 0.027 | 0.022 | notable |
| East Asian | 0.0061 | 0.0044 | notable |
| Finnish | 0.0028 | 0.0022 | notable |
| European (Non-Finnish) | 0.0033 | 0.0029 | notable |
| South Asian | 0.0083 | 0.0054 | notable |
| Other | 0.0035 | 0.0028 | notable |
dbNSFP Gene Annotations
Source:
- Disease
- DISEASE: Note=METTL27 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of METTL27 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease. {ECO:0000269|Ref.1}.;
Intolerance Scores
- RVIS EVS
- 1.31
- RVIS percentile EVS
- 94
Essentials
- Essential (gene trap)
- N