METTL27

Chr 7

methyltransferase like 27

Also known as: WBSCR27

NCBI Gene: 155368ENSG00000165171UniProt: Q8N6F8OMIM: 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.

OMIMResearchSummary from RefSeq
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
166 unique Pathogenic / Likely Pathogenic· 40 VUS of 220 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 OE0.39 (0.18–1.02)
0≤0.351.4
Missense OE1.11 (0.97–1.26)
0≤0.61.4
Synonymous OE1.15
0≤1.21.6
LoF obs/exp: 3 / 7.6Missense obs/exp: 161 / 145.5Syn Z: -0.96
DN
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

220 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic160
Likely Pathogenic6
VUS40
Likely Benign10
160
Pathogenic
6
Likely Pathogenic
40
VUS
10
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
160
0
160
Likely Pathogenic
0
0
6
0
6
VUS
0
35
5
0
40
Likely Benign
1
4
0
5
10
Benign
0
0
0
0
0
Total1391715216

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

View in ClinVar →

Protein Context — Lollipop Plot

METTL27 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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