METTL21C

Chr 13

methyltransferase 21C, AARS1 lysine

Also known as: C13orf39

NCBI Gene: 196541 ENSG00000139780 UniProt: Q5VZV1

METTL21C encodes a protein-lysine N-methyltransferase that methylates lysine-943 of AARS1 (alanyl-tRNA synthetase) and has heat shock protein binding activity. The gene is highly constrained against loss-of-function variants (pLI = 1.0), but no human disease associations have been established for METTL21C mutations. This gene follows autosomal inheritance patterns.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.45

Clinical Summary— METTL21C

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.45LOEUF

pLI 0.000

Z-score 0.45

OE 0.86 (0.53–1.45)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.08Z-score

OE missense 1.02 (0.89–1.17)

145 obs / 142.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.86 (0.53–1.45)

0≤0.351.4

Missense OE?1.02 (0.89–1.17)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 10 / 11.7Missense obs/exp: 145 / 142.4Syn Z: -0.26

This gene — mechanism propensity

0.6355th %ile

GOF

0.5465th %ile

LOF

0.2776th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.