METTL21A

Chr 2

methyltransferase 21A, HSPA lysine

Also known as: FAM119A, HCA557b, HSPA-KMT

This protein-lysine methyltransferase selectively trimethylates specific lysine residues in heat shock protein 70 (HSP70) family members, including HSPA1 and HSPA8. The gene is not highly constrained against loss-of-function variants, and currently no definitive human disease associations have been established for METTL21A mutations in the provided clinical data.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.36
Clinical SummaryMETTL21A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.36LOEUF
pLI 0.001
Z-score 0.83
OE 0.69 (0.381.36)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.04Z-score
OE missense 1.01 (0.871.17)
123 obs / 121.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.69 (0.381.36)
00.351.4
Missense OE1.01 (0.871.17)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 6 / 8.6Missense obs/exp: 123 / 121.7Syn Z: 0.81
DN
0.7035th %ile
GOF
0.5955th %ile
LOF
0.2092th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

METTL21A · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC