METTL25B

Chr 1

methyltransferase like 25B

Also known as: C1orf66, CGI-41, RRNAD1

NCBI Gene: 51093 ENSG00000143303 UniProt: Q96FB5

Predicted to enable rRNA (adenine-N6,N6-)-dimethyltransferase activity. Predicted to be involved in rRNA methylation. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

Research

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.21

Clinical Summary— METTL25B

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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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ClinVar Variants

76 VUS of 100 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.21LOEUF

pLI 0.000

Z-score 0.77

OE 0.83 (0.58–1.21)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.39Z-score

OE missense 0.94 (0.84–1.04)

265 obs / 283.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.83 (0.58–1.21)

0≤0.351.4

Missense OE?0.94 (0.84–1.04)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 19 / 23.0Missense obs/exp: 265 / 283.3Syn Z: 1.17

This gene — mechanism propensity

0.6455th %ile

GOF

0.4283th %ile

LOF

0.3162th %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

100 submitted variants in ClinVar

ClinVar

Classification Summary

VUS76

Likely Benign13

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	76	76
Likely Benign	13	13
Benign	0	0
Total	89	89

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap METTL25B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →