DOT1L
Basic information
Region (hg38): 19:2163933-2232578
Links
Phenotypes
GenCC
Source:
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn_genetic_diseases (184 variants)
- not_provided (74 variants)
- NIL-DESHWAR_NEURODEVELOPMENTAL_SYNDROME (7 variants)
- not_specified (1 variants)
- DOT1L-related_condition (1 variants)
- Developmental_disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DOT1L gene is commonly pathogenic or not. These statistics are base on transcript: NM_000032482.3. 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 | 20 | 27 | ||||
| missense | 186 | 25 | 219 | |||
| nonsense | 4 | |||||
| start loss | 0 | |||||
| frameshift | 5 | |||||
| splice donor/acceptor (+/-2bp) | 4 | |||||
| Total | 7 | 1 | 198 | 45 | 8 |
Highest pathogenic variant AF is 0.00000617994
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DOT1L | protein_coding | protein_coding | ENST00000398665 | 28 | 68430 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 5.20e-9 | 124563 | 0 | 5 | 124568 | 0.0000201 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.72 | 736 | 976 | 0.754 | 0.0000673 | 9847 |
| Missense in Polyphen | 329 | 520.01 | 0.63267 | 5497 | ||
| Synonymous | -3.42 | 566 | 472 | 1.20 | 0.0000389 | 3192 |
| Loss of Function | 7.17 | 3 | 65.8 | 0.0456 | 0.00000314 | 762 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000741 | 0.0000647 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000557 | 0.0000556 |
| Finnish | 0.0000469 | 0.0000464 |
| European (Non-Finnish) | 0.0000202 | 0.0000177 |
| Middle Eastern | 0.0000557 | 0.0000556 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones (PubMed:12123582). Binds to DNA (PubMed:12628190). {ECO:0000269|PubMed:12123582, ECO:0000269|PubMed:12628190}.;
- Pathway
- Lysine degradation - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Histone Modifications;PKMTs methylate histone lysines;Chromatin modifying enzymes;Lysine metabolism;Chromatin organization
(Consensus)
Recessive Scores
- pRec
- 0.141
Intolerance Scores
- loftool
- 0.0743
- rvis_EVS
- -3.18
- rvis_percentile_EVS
- 0.45
Haploinsufficiency Scores
- pHI
- 0.188
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.598
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Dot1l
- Phenotype
- normal 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); hematopoietic system phenotype; 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); neoplasm; embryo phenotype; immune system phenotype; limbs/digits/tail phenotype; vision/eye phenotype; growth/size/body region phenotype; cellular phenotype; muscle phenotype;
Zebrafish Information Network
- Gene name
- dot1l
- Affected structure
- intestinal villus
- Phenotype tag
- abnormal
- Phenotype quality
- decreased length
Gene ontology
- Biological process
- DNA damage checkpoint;chromatin silencing at telomere;positive regulation of cell population proliferation;telomere organization;histone H3-K79 methylation;positive regulation of transcription by RNA polymerase II;regulation of JAK-STAT cascade;regulation of transcription regulatory region DNA binding
- Cellular component
- chromosome, telomeric region;nucleus;nucleoplasm;protein-containing complex;intracellular membrane-bounded organelle
- Molecular function
- DNA binding;protein binding;histone-lysine N-methyltransferase activity;histone methyltransferase activity (H3-K79 specific);histone methyltransferase activity