KMT5A

lysine methyltransferase 5A, the group of SET domain containing|Lysine methyltransferases

Basic information

Region (hg38): 12:123384132-123409353

Previous symbols: [ "SETD8" ]

Links

ENSG00000183955 ∙ NCBI:387893 ∙ OMIM:607240 ∙ HGNC:29489 ∙ Uniprot:Q9NQR1 ∙ 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 KMT5A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KMT5A 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						0
missense			1			1
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	1	0	0

Variants in KMT5A

This is a list of pathogenic ClinVar variants found in the KMT5A region.

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

Position	Type	Phenotype	Significance	ClinVar
12-123395044-C-A		Malignant tumor of prostate	Uncertain significance (-)
12-123396376-CTT-C		EBV-positive nodal T- and NK-cell lymphoma	Likely benign (-)
12-123404929-C-G		not specified	Uncertain significance (Aug 30, 2021)
12-123404945-A-C		EBV-positive nodal T- and NK-cell lymphoma	Likely benign (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KMT5A	protein_coding	protein_coding	ENST00000402868	8	25586

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.985	0.0147	124791	0	2	124793	0.00000801

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.02	113	192	0.589	0.0000117	2278
Missense in Polyphen		17	77.644	0.21895		831
Synonymous	-0.154	81	79.3	1.02	0.00000571	681
Loss of Function	3.62	1	17.2	0.0581	9.96e-7	213

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000302	0.0000302
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000899	0.00000887
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis. Involved in chromosome condensation and proper cytokinesis. Nucleosomes are preferred as substrate compared to free histones. Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes. Plays a negative role in TGF-beta response regulation and a positive role in cell migration. {ECO:0000269|PubMed:12086618, ECO:0000269|PubMed:12121615, ECO:0000269|PubMed:15200950, ECO:0000269|PubMed:15933069, ECO:0000269|PubMed:15933070, ECO:0000269|PubMed:16517599, ECO:0000269|PubMed:17707234, ECO:0000269|PubMed:23478445}.
• Pathway: Lysine degradation - Homo sapiens (human);Histone Modifications;Gene expression (Transcription);Generic Transcription Pathway;PKMTs methylate histone lysines;RNA Polymerase II Transcription;Chromatin modifying enzymes;Lysine metabolism;Condensation of Prophase Chromosomes;Chromatin organization;Mitotic Prophase;Regulation of TP53 Activity through Methylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;M Phase;Cell Cycle;Cell Cycle, Mitotic;p53 pathway (Consensus)

Recessive Scores

• pRec: 0.140

Intolerance Scores

• rvis_EVS: 0.1
• rvis_percentile_EVS: 61.49

Haploinsufficiency Scores

• pHI: 0.138
• hipred: Y
• hipred_score: 0.801
• ghis: 0.499

Essentials

• essential_gene_gene_trap: K

Mouse Genome Informatics

• Gene name: Kmt5a
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; embryo 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)

Zebrafish Information Network

• Gene name: kmt5aa
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;cell cycle;peptidyl-lysine monomethylation;histone H4-K20 methylation;regulation of DNA damage response, signal transduction by p53 class mediator;negative regulation of transcription, DNA-templated;cell division;regulation of signal transduction by p53 class mediator
• Cellular component: nucleus;nucleoplasm;chromosome;cytosol
• Molecular function: p53 binding;transcription corepressor activity;protein binding;lysine N-methyltransferase activity;protein-lysine N-methyltransferase activity;histone-lysine N-methyltransferase activity;histone methyltransferase activity (H4-K20 specific)