ZCWPW2

Chr 3

zinc finger CW-type and PWWP domain containing 2

Also known as: ZCW2

ZCWPW2 encodes a histone methylation reader protein that binds to methylated lysine-4 on histone H3, with highest affinity for trimethylated H3K4, and is active in the nucleus. Mutations cause autosomal recessive neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy, with onset in infancy or early childhood. The gene is associated with severe developmental delay, seizures, and progressive spasticity affecting the central nervous system.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.03
Clinical SummaryZCWPW2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 70 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.03LOEUF
pLI 0.000
Z-score 1.47
OE 0.64 (0.411.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.91Z-score
OE missense 1.20 (1.061.34)
204 obs / 170.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.64 (0.411.03)
00.351.4
Missense OE1.20 (1.061.34)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 12 / 18.9Missense obs/exp: 204 / 170.7Syn Z: -0.82

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS70
Likely Benign4
15
Pathogenic
1
Likely Pathogenic
70
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
1
0
1
VUS
1
62
7
0
70
Likely Benign
0
3
1
0
4
Benign
0
0
0
0
0
Total16524090

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

View in ClinVar →

Protein Context — Lollipop Plot

ZCWPW2 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC