DNMT3B
DNA methyltransferase 3 beta, the group of PWWP domain containing|7BS C5-cytosine DNA/RNA methyltransferases
Basic information
Region (hg38): 20:32762385-32809359
Links
Phenotypes
GenCC
Source:
- immunodeficiency-centromeric instability-facial anomalies syndrome 1 (Definitive), mode of inheritance: AR
- immunodeficiency-centromeric instability-facial anomalies syndrome 1 (Definitive), mode of inheritance: AR
- immunodeficiency-centromeric instability-facial anomalies syndrome (Supportive), mode of inheritance: AR
- immunodeficiency-centromeric instability-facial anomalies syndrome 1 (Strong), mode of inheritance: AR
- immunodeficiency-centromeric instability-facial anomalies syndrome 1 (Strong), mode of inheritance: AR
- facioscapulohumeral muscular dystrophy (Supportive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Immunodeficiency-centromeric instability-facial anomalies syndrome 1 | AR | Allergy/Immunology/Infectious | Though the disorder may be clinically recognizable in many individuals, immunoglobulin supplementation can be beneficial, as can prophylaxis and early and aggressive treatment of infections | Allergy/Immunology/Infectious; Neurologic | 8076938; 10555141; 10647011; 11102980; 17893117 |
ClinVar
This is a list of variants' phenotypes submitted to
- Centromeric_instability_of_chromosomes_1,9_and_16_and_immunodeficiency (775 variants)
- Immunodeficiency-centromeric_instability-facial_anomalies_syndrome_1 (91 variants)
- Inborn_genetic_diseases (88 variants)
- not_provided (62 variants)
- DNMT3B-related_disorder (27 variants)
- not_specified (14 variants)
- Facioscapulohumeral_muscular_dystrophy_4,_digenic (11 variants)
- Kabuki_syndrome_1 (1 variants)
- See_cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNMT3B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006892.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 281 | 294 | ||||
| missense | 17 | 243 | 16 | 286 | ||
| nonsense | 10 | 10 | ||||
| start loss | 0 | |||||
| frameshift | 6 | |||||
| splice donor/acceptor (+/-2bp) | 5 | |||||
| Total | 22 | 24 | 251 | 297 | 7 |
Highest pathogenic variant AF is 0.000039652
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DNMT3B | protein_coding | protein_coding | ENST00000328111 | 22 | 46972 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.200 | 0.800 | 125731 | 0 | 17 | 125748 | 0.0000676 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.50 | 418 | 514 | 0.814 | 0.0000358 | 5565 |
| Missense in Polyphen | 192 | 300.35 | 0.63925 | 3376 | ||
| Synonymous | -0.163 | 214 | 211 | 1.01 | 0.0000156 | 1669 |
| Loss of Function | 5.26 | 13 | 55.2 | 0.236 | 0.00000383 | 562 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.0000883 | 0.0000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000980 | 0.0000980 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co- repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing (By similarity). In association with DNMT1 and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Isoforms 4 and 5 are probably not functional due to the deletion of two conserved methyltransferase motifs. Function as transcriptional corepressor by associating with ZHX1. Required for DUX4 silencing in somatic cells (PubMed:27153398). {ECO:0000250, ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:17303076, ECO:0000269|PubMed:18413740, ECO:0000269|PubMed:18567530, ECO:0000269|PubMed:27153398}.;
- Disease
- DISEASE: Immunodeficiency-centromeric instability-facial anomalies syndrome 1 (ICF1) [MIM:242860]: A rare disorder characterized by a variable immunodeficiency resulting in recurrent infections, facial anomalies, and branching of chromosomes 1, 9, and 16. Other variable symptoms include growth retardation, failure to thrive, and psychomotor retardation. Laboratory studies show limited hypomethylation of DNA in a small fraction of the genome in some, but not all, patients. {ECO:0000269|PubMed:10555141, ECO:0000269|PubMed:10588719, ECO:0000269|PubMed:10647011, ECO:0000269|PubMed:11102980, ECO:0000269|PubMed:15580563, ECO:0000269|PubMed:21120685, ECO:0000269|PubMed:27734333}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Facioscapulohumeral muscular dystrophy 2 (FSHD2) [MIM:158901]: A degenerative muscle disease characterized by slowly progressive weakness of the muscles of the face, upper-arm, and shoulder girdle. The onset of symptoms usually occurs in the first or second decade of life. Affected individuals usually present with impairment of upper extremity elevation. This tends to be followed by facial weakness, primarily involving the orbicularis oris and orbicularis oculi muscles. {ECO:0000269|PubMed:27153398}. Note=The gene represented in this entry may act as a disease modifier. DNMT3B mutations lead to DUX4 expression in somatic tissues, including muscle cells, when an haplotype on chromosome 4 is permissive for DUX4 expression. Ectopic expression of DUX4 in skeletal muscle activates the expression of stem cell and germline genes, and, when overexpressed in somatic cells, DUX4 can ultimately lead to cell death.;
- Pathway
- Cysteine and methionine metabolism - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);miR-targeted genes in lymphocytes - TarBase;One Carbon Metabolism;Trans-sulfuration and one carbon metabolism;Mesodermal Commitment Pathway;Hematopoietic Stem Cell Gene Regulation by GABP alpha-beta Complex;NoRC negatively regulates rRNA expression;Negative epigenetic regulation of rRNA expression;DNA methylation;Epigenetic regulation of gene expression;Gene expression (Transcription);Methionine and cysteine metabolism;PRC2 methylates histones and DNA
(Consensus)
Recessive Scores
- pRec
- 0.0949
Intolerance Scores
- loftool
- 0.00992
- rvis_EVS
- -1.7
- rvis_percentile_EVS
- 2.54
Haploinsufficiency Scores
- pHI
- 0.642
- hipred
- Y
- hipred_score
- 0.770
- ghis
- 0.530
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Dnmt3b
- Phenotype
- nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; skeleton phenotype; embryo phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; neoplasm; endocrine/exocrine gland phenotype; craniofacial phenotype; cellular phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- dnmt3bb.2
- Affected structure
- head
- Phenotype tag
- abnormal
- Phenotype quality
- decreased size
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;response to hypoxia;DNA methylation;response to toxic substance;response to ionizing radiation;positive regulation of gene expression;response to activity;response to caffeine;response to estradiol;response to vitamin A;response to cocaine;positive regulation of neuron differentiation;negative regulation of gene expression, epigenetic;positive regulation of histone H3-K4 methylation;negative regulation of histone H3-K9 methylation;cellular response to hyperoxia;cellular response to dexamethasone stimulus;C-5 methylation of cytosine
- Cellular component
- nucleus;nucleoplasm;intracellular membrane-bounded organelle
- Molecular function
- DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;chromatin binding;transcription corepressor activity;DNA (cytosine-5-)-methyltransferase activity;protein binding;DNA-methyltransferase activity;histone deacetylase binding;metal ion binding