DNMT3L

DNA methyltransferase 3 like, the group of 7BS C5-cytosine DNA/RNA methyltransferases

Basic information

Region (hg38): 21:44246339-44262216

Links

ENSG00000142182 ∙ NCBI:29947 ∙ OMIM:606588 ∙ HGNC:2980 ∙ Uniprot:Q9UJW3 ∙ 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 DNMT3L gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNMT3L 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				1		1
missense			20	1		21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	20	2	0

Variants in DNMT3L

This is a list of pathogenic ClinVar variants found in the DNMT3L region.

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

Position	Type	Phenotype	Significance	ClinVar
21-44246500-G-A		not specified	Uncertain significance (Dec 28, 2022)
21-44246542-G-A		not specified	Uncertain significance (Aug 15, 2023)
21-44249054-C-T		not specified	Uncertain significance (Nov 01, 2022)
21-44249056-C-T		not specified	Likely benign (Aug 12, 2021)
21-44249057-G-A		not specified	Uncertain significance (Mar 01, 2024)
21-44249081-C-T		not specified	Uncertain significance (May 30, 2024)
21-44249082-G-A			Likely benign (Jun 01, 2022)
21-44250873-C-A		not specified	Uncertain significance (Mar 15, 2024)
21-44250926-G-A		not specified	Uncertain significance (Dec 13, 2022)
21-44250927-G-T		not specified	Uncertain significance (Dec 02, 2021)
21-44251626-G-C		not specified	Uncertain significance (Nov 15, 2021)
21-44251632-G-A		not specified	Uncertain significance (Oct 26, 2022)
21-44254649-C-G		not specified	Likely benign (May 28, 2024)
21-44254666-G-A		not specified	Uncertain significance (Jul 20, 2022)
21-44256116-C-G		not specified	Uncertain significance (Mar 11, 2022)
21-44258559-C-A		not specified	Uncertain significance (Jul 05, 2022)
21-44258566-C-T		not specified	Uncertain significance (Sep 14, 2022)
21-44258647-G-A		not specified	Uncertain significance (Jun 07, 2023)
21-44258663-C-T		not specified	Uncertain significance (May 05, 2023)
21-44258690-A-G		not specified	Uncertain significance (Aug 21, 2023)
21-44259456-C-T		not specified	Uncertain significance (Mar 15, 2024)
21-44259472-C-G		not specified	Uncertain significance (Jun 21, 2023)
21-44259476-C-G		not specified	Uncertain significance (Apr 17, 2024)
21-44259506-T-C		not specified	Uncertain significance (Nov 10, 2022)
21-44260801-T-C		not specified	Uncertain significance (Feb 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNMT3L	protein_coding	protein_coding	ENST00000270172	11	15878

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.41e-13	0.0727	125613	0	126	125739	0.000501

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.103	237	242	0.981	0.0000152	2509
Missense in Polyphen		71	78.549	0.90389		852
Synonymous	0.634	98	106	0.922	0.00000746	759
Loss of Function	0.471	20	22.4	0.893	0.00000121	226

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000374	0.000370
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.000370	0.000370
European (Non-Finnish)	0.000810	0.000800
Middle Eastern	0.000326	0.000326
South Asian	0.000427	0.000425
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytically inactive regulatory factor of DNA methyltransferases that can either promote or inhibit DNA methylation depending on the context (By similarity). Essential for the function of DNMT3A and DNMT3B: activates DNMT3A and DNMT3B by binding to their catalytic domain (PubMed:17687327). Acts by accelerating the binding of DNA and S-adenosyl-L-methionine (AdoMet) to the methyltransferases and dissociates from the complex after DNA binding to the methyltransferases (PubMed:17687327). Recognizes unmethylated histone H3 lysine 4 (H3K4me0) and induces de novo DNA methylation by recruitment or activation of DNMT3 (PubMed:17687327). Plays a key role in embryonic stem cells and germ cells (By similarity). In germ cells, required for the methylation of imprinted loci together with DNMT3A (By similarity). In male germ cells, specifically required to methylate retrotransposons, preventing their mobilization (By similarity). Plays a key role in embryonic stem cells (ESCs) by acting both as an positive and negative regulator of DNA methylation (By similarity). While it promotes DNA methylation of housekeeping genes together with DNMT3A and DNMT3B, it also acts as an inhibitor of DNA methylation at the promoter of bivalent genes (By similarity). Interacts with the EZH2 component of the PRC2/EED-EZH2 complex, preventing interaction of DNMT3A and DNMT3B with the PRC2/EED-EZH2 complex, leading to maintain low methylation levels at the promoters of bivalent genes (By similarity). Promotes differentiation of ESCs into primordial germ cells by inhibiting DNA methylation at the promoter of RHOX5, thereby activating its expression (By similarity). {ECO:0000250|UniProtKB:Q9CWR8, ECO:0000269|PubMed:17687327}.
• Pathway: Trans-sulfuration and one carbon metabolism;Preimplantation Embryo;DNA methylation;Epigenetic regulation of gene expression;Gene expression (Transcription) (Consensus)

Recessive Scores

• pRec: 0.179

Intolerance Scores

• loftool: 0.511
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.65

Haploinsufficiency Scores

• pHI: 0.114
• hipred: N
• hipred_score: 0.341
• ghis: 0.427

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.565

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dnmt3l
• Phenotype: endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; embryo 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); 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); reproductive system 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)

Gene ontology

• Biological process: DNA methylation;regulation of gene expression by genetic imprinting;regulation of transcription by RNA polymerase II;male meiosis I;spermatogenesis;DNA methylation on cytosine;DNA methylation involved in gamete generation;positive regulation of catalytic activity;negative regulation of transcription, DNA-templated;stem cell differentiation;negative regulation of DNA methylation;positive regulation of DNA methylation
• Cellular component: nucleus;cytosol;ESC/E(Z) complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;protein binding;enzyme activator activity;enzyme binding;metal ion binding