VCPKMT

protein-coding

valosin containing protein lysine methyltransferase, the group of 7BS protein lysine methyltransferases

Gene summary

Enables ATPase binding activity and protein-lysine N-methyltransferase activity. Involved in negative regulation of ATP-dependent activity and peptidyl-lysine trimethylation. Located in cytosol. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C14orf138
METTL21D

MANE transcript

NM_024558.3

Inheritance

—

ClinVar variants

U:48

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.27

Max pathogenic AF

—

Genomic locus

chr14:50,108,632-50,116,600

External References & Databases

Ensembl (ENSG00000100483)

Transcript & Mutation Effects

hg38 • Region Span ~8.0 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 VCPKMT variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 48

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024558.3. 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						0
missense			47 clinvar			47
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	48	0	0	48

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024558.3	RefSeq	NP_078834.2	6	MANE Select
ENST00000395860.7	Ensembl	ENSP00000379201.2	6	MANE Select
NM_001040662.2	RefSeq	NP_001035752.1	5	Standard
ENST00000395859.2	Ensembl	ENSP00000379200.2	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Protein methylation

Biological Process

protein methylation
peptidyl-lysine methylation
peptidyl-lysine trimethylation
negative regulation of ATPase activity

Molecular Function

protein binding
protein-lysine N-methyltransferase activity
ATPase binding

Cellular Component

cytoplasm
cytosol
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395860
Coding exons: 6
Length: 7969
Individuals with no LoFs: 125649
Homozygous LoFs: 1
Heterozygous LoFs: 98
Defined: 125748
p: 0.000394

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.61	169	119	1.42	0.00000551	1474
Missense (PolyPhen)		36	39.137	0.91986		444
Synonymous	-2.18	69	49.5	1.39	0.00000245	442
Loss of Function	-0.836	14	11.0	1.27	5.30e-7	136

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0020	0.0020	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.000084	0.000079	rare
South Asian	0.0016	0.0015	notable
Other	0.00052	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protein-lysine N-methyltransferase that specifically trimethylates 'Lys-315' of VCP/p97; this modification may decrease VCP ATPase activity. {ECO:0000269|PubMed:22948820, ECO:0000269|PubMed:23349634}.;

Recessive Scores

pRec: 0.100

Intolerance Scores

RVIS EVS: -0.01
RVIS percentile EVS: 53.51

Essentials

Essential (gene trap): N

Gene Damage Prediction

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