METTL21C

protein-coding

methyltransferase 21C, AARS1 lysine, the group of 7BS protein lysine methyltransferases

Gene summary

Enables heat shock protein binding activity and protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine methylation. Located in cytoplasm and nucleus. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C13orf39

MANE transcript

NM_001010977.3

Inheritance

—

ClinVar variants

U:41B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr13:102,685,747-102,695,044

External References & Databases

Ensembl (ENSG00000139780)

Transcript & Mutation Effects

hg38 • Region Span ~9.3 kb

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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 METTL21C variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 45

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001010977.3. 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				1 clinvar		1
missense			41 clinvar	4 clinvar		45
nonsense						0
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)						0
Total	0	0	41	6	0	47

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001010977.3	RefSeq	NP_001010977.1	4	MANE Select
ENST00000267273.7	Ensembl	ENSP00000267273.5	4	MANE Select
ENST00001131541.1	Ensembl	ENSP00000803886.1	4	Standard
XM_047430117.1	RefSeq	XP_047286073.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein methylation
skeletal muscle tissue development
hormone-mediated apoptotic signaling pathway
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
peptidyl-lysine methylation

Molecular Function

protein binding
protein-lysine N-methyltransferase activity
heat shock protein binding

Cellular Component

nucleus
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000267273
Coding exons: 4
Length: 8761
Individuals with no LoFs: 125630
Homozygous LoFs: 0
Heterozygous LoFs: 118
Defined: 125748
p: 0.000469

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0760	145	142	1.02	0.00000738	1701
Missense (PolyPhen)		56	56.034	0.9994		693
Synonymous	-0.255	62	59.5	1.04	0.00000357	511
Loss of Function	0.452	10	11.7	0.857	4.93e-7	144

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.0011	0.0011	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0018	0.0018	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00028	0.00026	rare
South Asian	0.00026	0.00026	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protein-lysine methyltransferase. {ECO:0000269|PubMed:22948820}.;

Intolerance Scores

RVIS EVS: 0.93
RVIS percentile EVS: 89.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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