METTL21C

Chr 13

methyltransferase 21C, AARS1 lysine

Also known as: C13orf39

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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
100
P/LP submissions
0%
P/LP missense
1.45
LOEUF
DN
Mechanism· predicted
Clinical SummaryMETTL21C
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
100 unique Pathogenic / Likely Pathogenic· 46 VUS of 154 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.45LOEUF
pLI 0.000
Z-score 0.45
OE 0.86 (0.531.45)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.08Z-score
OE missense 1.02 (0.891.17)
145 obs / 142.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.86 (0.531.45)
00.351.4
Missense OE1.02 (0.891.17)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 10 / 11.7Missense obs/exp: 145 / 142.4Syn Z: -0.26
DN
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.

ClinVar Variant Classifications

154 submitted variants in ClinVar

Classification Summary

Pathogenic99
Likely Pathogenic1
VUS46
Likely Benign6
99
Pathogenic
1
Likely Pathogenic
46
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
99
0
99
Likely Pathogenic
0
0
1
0
1
VUS
0
40
6
0
46
Likely Benign
0
4
1
1
6
Benign
0
0
0
0
0
Total0441071152

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

METTL21C · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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