EZH1

Chr 17

enhancer of zeste 1 polycomb repressive complex 2 subunit

Also known as: KMT6B

NCBI Gene: 2145 ENSG00000108799 UniProt: Q92800

EZH1 is a component of a noncanonical Polycomb repressive complex-2 (PRC2) that mediates methylation of histone H3 (see MIM 602812) lys27 (H3K27) and functions in the maintenance of embryonic stem cell pluripotency and plasticity (Shen et al., 2008 [PubMed 19026780]).[supplied by OMIM, Mar 2009]

Active trials

Pathogenic / LP

ClinVar variants

Pubs (1 yr)

4.2

Missense Z· constrained

0.42

LOEUF

Clinical Summary— EZH1

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

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ClinVar Variants

12 Pathogenic / Likely Pathogenic· 61 VUS of 73 total submissions

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Clinical Trials

7 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.42LOEUF

pLI 0.043

Z-score 4.66

OE 0.26 (0.17–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

4.20Z-score

OE missense 0.42 (0.38–0.48)

179 obs / 421.6 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.26 (0.17–0.42)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.42 (0.38–0.48)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.79

0≤1.21.6

LoF obs/exp: 12 / 46.1Missense obs/exp: 179 / 421.6Syn Z: 1.95

ClinVar Variant Classifications

73 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic6

VUS61

Pathogenic

Likely Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	6	6
Likely Pathogenic	2	2	2	6
VUS	1	59	1	61
Likely Benign	0	0	0	0
Benign	0	0	0	0
Total	3	61	9	73

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

View in ClinVar →

Protein Context — Lollipop Plot

EZH1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

EZH1-related neurodevelopmental disorder

moderate

ADGain Of FunctionAltered Gene Product Structure

Dev. Disorders

G2P ↗

missense variant

EZH1-related neurodevelopmental disorder

moderate

ARLoss Of FunctionAbsent Gene Product, Decreased Gene Product Level

Dev. Disorders

G2P ↗

splice acceptor variantstop gained

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Lymphoma, Follicular

A Study of Tazemetostat on Safety in Participants With Relapsed or Refractory Follicular Lymphoma With Enhancer of Zeste Homolog 2 (EZH2) Gene Mutation in Japan

ACTIVE NOT RECRUITING

NCT05228158Eisai Co., Ltd.Started 2021-08-16

Tazemetostat

Peripheral T Cells Lymphoma (PTCL)

Zeprumetostat, Azacitidine Combined With Lipo-MIT in R/R PTCL

RECRUITING

NCT07372352Phase PHASE2The First Affiliated Hospital of Soochow UniversityStarted 2026-01-15

ZeprumetostatAzacitidine (AZA)Mitoxantrone Hydrochloride Liposome

Recurrent B-Cell Non-Hodgkin LymphomaRecurrent Diffuse Large B-Cell Lymphoma Germinal Center B-Cell TypeRecurrent Follicular Lymphoma

Testing the Safety of the Anti-cancer Drugs Tazemetostat and Belinostat in Patients With Lymphomas That Have Resisted Treatment

RECRUITING

NCT05627245Phase PHASE1National Cancer Institute (NCI)Started 2023-03-01