METTL22

Chr 16

methyltransferase 22, Kin17 lysine

Also known as: C16orf68

NCBI Gene: 79091 ENSG00000067365 UniProt: Q9BUU2 OMIM: 615261

The protein is a lysine methyltransferase that trimethylates the DNA repair and replication protein KIN17 at lysine-135. Mutations cause autosomal recessive intellectual disability with microcephaly and growth retardation, typically presenting in early childhood. The gene shows minimal constraint against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the non-histone lysine methyltransferases. It interacts with its substrate, Kin17, which is involved in DNA repair and replication and mRNA processing. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

OMIM ResearchGenerating clinical summary…

LOEUF 1.35

Clinical Summary— METTL22

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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

93 VUS of 131 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?

1.35LOEUF

pLI 0.000

Z-score 0.26

OE 0.94 (0.67–1.35)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.98Z-score

OE missense 1.36 (1.24–1.49)

331 obs / 243.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.94 (0.67–1.35)

0≤0.351.4

Missense OE?1.36 (1.24–1.49)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 21 / 22.3Missense obs/exp: 331 / 243.8Syn Z: -1.15

ClinVar Variant Classifications

131 submitted variants in ClinVar

ClinVar

Classification Summary

VUS93

Likely Benign11

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	93	0	0	93
Likely Benign	8	2	1	11
Benign	0	0	0	0
Total	101	2	1	104

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap METTL22 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →