DOT1L

DOT1 like histone lysine methyltransferase, the group of 7BS protein lysine methyltransferases|Lysine methyltransferases

Basic information

Region (hg38): 19:2163932-2232578

Links

ENSG00000104885 ∙ NCBI:84444 ∙ OMIM:607375 ∙ HGNC:24948 ∙ Uniprot:Q8TEK3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DOT1L gene.

• Inborn genetic diseases (54 variants)
• not provided (28 variants)
• not specified (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				9	6	15
missense			54	5	1	60
nonsense			1			1
start loss						0
frameshift		1				1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1		3	4
non coding				1	1	2
Total	0	1	56	15	8

Variants in DOT1L

This is a list of pathogenic ClinVar variants found in the DOT1L region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-2164274-C-G			Benign (Dec 31, 2019)
19-2189750-G-A			Benign (Jul 20, 2018)
19-2189786-C-G			Uncertain significance (Oct 25, 2022)
19-2191147-G-A			Uncertain significance (Apr 28, 2022)
19-2191155-C-T		Inborn genetic diseases	Likely benign (Dec 14, 2023)
19-2191212-C-T			Benign (Dec 28, 2017)
19-2193789-C-T			Benign (Dec 28, 2017)
19-2194524-C-T		Inborn genetic diseases	Uncertain significance (Jul 10, 2023)
19-2199918-G-A		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
19-2206739-C-T			Likely benign (Jan 01, 2023)
19-2207673-G-A		Inborn genetic diseases	Uncertain significance (Jan 04, 2022)
19-2210487-G-A		Inborn genetic diseases	Uncertain significance (May 01, 2023)
19-2210490-G-A		Inborn genetic diseases	Uncertain significance (Apr 18, 2023)
19-2210498-C-T			Benign (Apr 10, 2018)
19-2210688-G-A		Inborn genetic diseases	Uncertain significance (Aug 08, 2022)
19-2210737-C-T			Likely benign (Dec 01, 2022)
19-2210796-C-T		Inborn genetic diseases	Uncertain significance (Nov 18, 2022)
19-2210816-G-A		Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
19-2211142-G-A			Likely benign (Oct 01, 2022)
19-2211176-G-A		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
19-2211180-C-T		Inborn genetic diseases	Uncertain significance (Jun 03, 2022)
19-2213600-A-C		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
19-2213615-G-A		Inborn genetic diseases	Uncertain significance (Sep 06, 2022)
19-2213622-T-G		Inborn genetic diseases	Uncertain significance (Sep 22, 2023)
19-2213632-T-G		Inborn genetic diseases	Uncertain significance (Nov 01, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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