MBD1
protein-codingmethyl-CpG binding domain protein 1, the group of Zinc fingers CXXC-type|Methyl-CpG binding domain containing
Gene summary
The protein encoded by this gene is a member of a family of nuclear proteins related by the presence of a methyl-CpG binding domain (MBD). These proteins are capable of binding specifically to methylated DNA, and some members can also repress transcription from methylated gene promoters. This protein contains multiple domains: MBD at the N-terminus that functions both in binding to methylated DNA and in protein interactions; several CXXC-type zinc finger domains that mediate binding to non-methylated CpG dinucleotides; transcriptional repression domain (TRD) at the C-terminus that is involved in transcription repression and in protein interactions. Numerous alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Feb 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.9 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 MBD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015846.4. 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 | 1 | 9 | ||
| missense | 65 | 5 | 70 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 79 | 10 | 1 | 90 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056671.2 | 15 | MANE Select | |
| Ensembl | ENSP00000269468.5 | 15 | MANE Select | |
| RefSeq | NP_001191065.1 | 15 | Standard | |
| RefSeq | NP_001191066.1 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- methylation-dependent chromatin silencing
- transcription by RNA polymerase II
- negative regulation of transcription, DNA-templated
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- protein binding
- zinc ion binding
- methyl-CpG binding
Cellular Component
- nucleus
- nucleoplasm
- chromosome
- nuclear matrix
- nuclear speck
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000590208
- Coding exons
- 15
- Length
- 14893
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125748
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.99 | 290 | 403 | 0.721 | 0.0000281 | 4184 |
| Missense (PolyPhen) | 68 | 167.1 | 0.40695 | 1705 | ||
| Synonymous | -0.509 | 160 | 152 | 1.05 | 0.00000962 | 1351 |
| Loss of Function | 5.07 | 5 | 39.3 | 0.127 | 0.00000252 | 411 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0.00013 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional repressor that binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binding is abolished by the presence of 7-mG that is produced by DNA damage by methylmethanesulfonate (MMS). Acts as transcriptional repressor and plays a role in gene silencing by recruiting AFT7IP, which in turn recruits factors such as the histone methyltransferase SETDB1. Probably forms a complex with SETDB1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Isoform 1 and isoform 2 can also repress transcription from unmethylated promoters. {ECO:0000269|PubMed:10454587, ECO:0000269|PubMed:10648624, ECO:0000269|PubMed:12665582, ECO:0000269|PubMed:12697822, ECO:0000269|PubMed:12711603, ECO:0000269|PubMed:14555760, ECO:0000269|PubMed:14610093, ECO:0000269|PubMed:15327775, ECO:0000269|PubMed:9207790, ECO:0000269|PubMed:9774669}.;
Recessive Scores
- pRec
- 0.156
Intolerance Scores
- LoFtool
- 0.0163
- RVIS EVS
- -0.75
- RVIS percentile EVS
- 13.58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.885
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |