METTL23

Chr 17AR

methyltransferase 23, arginine

Also known as: C17orf95, MRT44

NCBI Gene: 124512UniProt: Q86XA0

The protein encoded by this gene functions as a transcription factor regulator in the transcriptional pathway for human cognition. It is a partner of the alpha subunit of the GA-binding protein transcription factor. Mutations in this gene cause mild autosomal recessive intellectual disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 44MIM #615942
AR
0
Active trials
96
ClinVar variants
33
Pathogenic / LP
-1.0
Missense Z
1.77
LOEUF
6
Pubs (2 yr)
Clinical Summary— METTL23
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 52 VUS of 96 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.77LOEUF
pLI 0.000
Z-score -0.30
OE 1.11 (0.68–1.77)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.97Z-score
OE missense 1.28 (1.10–1.49)
123 obs / 96.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.11 (0.68–1.77)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.28 (1.10–1.49)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.21
0≤1.21.6
LoF obs/exp: 10 / 9.0Missense obs/exp: 123 / 96.1Syn Z: -0.96

ClinVar Variant Classifications

96 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic12
VUS52
Likely Benign7
Conflicting4
21
Pathogenic
12
Likely Pathogenic
52
VUS
7
Likely Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
13
0
21
Likely Pathogenic
9
0
3
0
12
VUS
2
43
7
0
52
Likely Benign
0
4
1
2
7
Benign
0
0
0
0
0
Conflicting
—4
Total194724296

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

View in ClinVar →

Protein Context — Lollipop Plot

METTL23 · protein map & ClinVar variants

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

Gene2Phenotype Curations

METTL23-related intellectual disability

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal recessive 44

MIM #615942

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants.
Khan A et al.·Genes (Basel)
2020Case report
METTL23 Variants and Patients With Normal-Tension Glaucoma.
Scheetz TE et al.·JAMA Ophthalmol
2024Cohort
Molecular genetics of inherited normal tension glaucoma.
Pan Y et al.·Indian J Ophthalmol
2024Review
Further delineation of METTL23-associated intellectual disability.
Almannai M et al.·Am J Med Genet A
2020Case report
Exome Sequencing and Congenital Heart Disease in Sub-Saharan Africa.
Ekure EN et al.·Circ Genom Precis Med
2021
Exome sequencing revealed a novel homozygous METTL23 gene mutation leading to familial mild intellectual disability with dysmorphic features.
Smaili W et al.·Eur J Med Genet
2020Case report
Exome sequencing reveals genetic heterogeneity in consanguineous Pakistani families with neurodevelopmental and neuromuscular disorders.
Bibi A et al.·Am J Med Genet C Semin Med Genet
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients