KMT5A

protein-coding

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

Gene summary

The protein encoded by this gene is a protein-lysine N-methyltransferase that can monomethylate Lys-20 of histone H4 to effect transcriptional repression of some genes. The encoded protein is required for cell proliferation and plays a role in chromatin condensation. [provided by RefSeq, May 2016]

Previous symbols:

SETD8

MANE transcript

NM_020382.7

Inheritance

—

ClinVar variants

U:5B:3

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr12:123,384,132-123,409,353

External References & Databases

Ensembl (ENSG00000183955)

Transcript & Mutation Effects

hg38 • Region Span ~25.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KMT5A variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 3

EBV-positive nodal T- and NK-cell lymphomaTotal: 2

not providedTotal: 2

Prostate cancerTotal: 1

Retinal capillary hemangiomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020382.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			4 clinvar	1 clinvar		5
nonsense						0
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	5	3	0	8

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020382.7	RefSeq	NP_065115.3	8	MANE Select
ENST00000402868.8	Ensembl	ENSP00000384629.3	8	MANE Select
NM_001324504.2	RefSeq	NP_001311433.1	9	Standard
NM_001324505.2	RefSeq	NP_001311434.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
kmt5aa	Danio rerio	Structure: post-vent region Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

kmt5aa

Danio rerio

Structure: post-vent region

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysine degradation - Homo sapiens (human)
Histone Modifications
Gene expression (Transcription)
Generic Transcription Pathway
PKMTs methylate histone lysines

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

Molecular Function

p53 binding
transcription corepressor activity
protein binding
lysine N-methyltransferase activity
protein-lysine N-methyltransferase activity

Cellular Component

nucleus
nucleoplasm
chromosome
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000402868
Coding exons: 8
Length: 25586
Individuals with no LoFs: 124791
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 124793
p: 0.00000801

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.02	113	192	0.589	0.0000117	2278
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000090	0.0000089	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.140

Intolerance Scores

RVIS EVS: 0.1
RVIS percentile EVS: 61.49

Essentials

Essential (gene trap): K