METTL23

Chr 17AR

methyltransferase 23, arginine

Also known as: C17orf95, MRT44

NCBI Gene: 124512 ENSG00000181038 UniProt: Q86XA0 OMIM: 615262

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.771 OMIM phenotype

Clinical Summary— METTL23

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Gene-Disease Validity (ClinGen)

intellectual disability · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

20 unique Pathogenic / Likely Pathogenic· 49 VUS of 88 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.97Z-score

OE missense 1.28 (1.10–1.49)

123 obs / 96.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.11 (0.68–1.77)

0≤0.351.4

Missense OE?1.28 (1.10–1.49)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 10 / 9.0Missense obs/exp: 123 / 96.1Syn Z: -0.96

ClinVar Variant Classifications

88 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9

Likely Pathogenic11

VUS49

Likely Benign7

Conflicting4

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	9	0	0	0	9
Likely Pathogenic	9	1	1	0	11
VUS	4	43	2	0	49
Likely Benign	0	4	1	2	7
Benign	0	0	0	0	0
Conflicting	—				4
Total	22	48	4	2	80

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap METTL23 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →