SETD6

Chr 16

SET domain containing 6, protein lysine methyltransferase

This gene encodes a methyltransferase that monomethylates histone H2AZ and the RELA subunit of NF-kappa-B, thereby regulating transcription and maintaining embryonic stem cell self-renewal. Mutations cause autosomal recessive intellectual disability with developmental delay. The gene shows minimal constraint against loss-of-function variants based on population genetic data.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.63
Clinical SummarySETD6
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 110 VUS of 168 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.63LOEUF
pLI 0.000
Z-score -0.74
OE 1.17 (0.851.63)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.39Z-score
OE missense 1.07 (0.971.18)
270 obs / 252.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.17 (0.851.63)
00.351.4
Missense OE1.07 (0.971.18)
00.61.4
Synonymous OE1.26
01.21.6
LoF obs/exp: 25 / 21.3Missense obs/exp: 270 / 252.6Syn Z: -2.11

ClinVar Variant Classifications

168 submitted variants in ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic6
VUS110
Likely Benign18
Benign4
20
Pathogenic
6
Likely Pathogenic
110
VUS
18
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
19
0
20
Likely Pathogenic
0
2
4
0
6
VUS
2
99
9
0
110
Likely Benign
0
4
7
7
18
Benign
0
0
2
2
4
Total3105419158

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

View in ClinVar →

Protein Context — Lollipop Plot

SETD6 · 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

No active trials found for this gene.

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Clinical Literature
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