METTL27

Chr 7

methyltransferase like 27

Also known as: WBSCR27

NCBI Gene: 155368 ENSG00000165171 UniProt: Q8N6F8 OMIM: 612546

The protein belongs to the ubiE/COQ5 methyltransferase family and is involved in methylation reactions. METTL27 is deleted as part of the contiguous gene deletion at 7q11.22-q11.23 that causes Williams syndrome, a multisystem developmental disorder. The gene shows tolerance to loss-of-function variants in the general population (pLI 0.06, LOEUF 1.02), suggesting its deletion may contribute to but not solely cause the Williams syndrome phenotype.

OMIM ResearchSummary from RefSeq

This gene encodes a protein belonging to ubiE/COQ5 methyltransferase family. The gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.22-q11.23. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.02

Clinical Summary— METTL27

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.06) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

35 VUS of 49 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?

1.02LOEUF

pLI 0.060

Z-score 1.55

OE 0.39 (0.18–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.46Z-score

OE missense 1.11 (0.97–1.26)

161 obs / 145.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.39 (0.18–1.02)

0≤0.351.4

Missense OE?1.11 (0.97–1.26)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 3 / 7.6Missense obs/exp: 161 / 145.5Syn Z: -0.96

This gene — mechanism propensity

0.6936th %ile

GOF

0.5955th %ile

LOF

0.2774th %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

49 submitted variants in ClinVar

ClinVar

Classification Summary

VUS35

Likely Benign10

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	0	35	0	35
Likely Benign	1	4	5	10
Benign	0	0	0	0
Total	1	39	5	45

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

View in ClinVar →

167 pathogenic / likely-pathogenic (of 172) ClinVar copy-number / structural variants overlap METTL27 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →