ZCWPW1

Chr 7

zinc finger CW-type and PWWP domain containing 1

Also known as: ZCW1

NCBI Gene: 55063ENSG00000078487UniProt: Q9H0M4

Enables histone reader activity; methyl-CpG binding activity; and methylated histone binding activity. Predicted to be involved in meiosis I; positive regulation of DNA metabolic process; and spermatogenesis. Predicted to act upstream of or within homologous chromosome pairing at meiosis. Predicted to be located in XY body. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2025]

117
ClinVar variants
21
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ZCWPW1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 86 VUS of 117 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.96LOEUF
pLI 0.000
Z-score 1.73
OE 0.70 (0.51–0.96)
Tolerant

Typical tolerance to LoF variation

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.
1.13Z-score
OE missense 0.83 (0.75–0.91)
286 obs / 345.1 exp
Tolerant

Mild missense constraint

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.0.70 (0.51–0.96)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.75–0.91)
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.0.91
0≤1.21.6
LoF obs/exp: 26 / 37.4Missense obs/exp: 286 / 345.1Syn Z: 0.77

ClinVar Variant Classifications

117 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic2
VUS86
Likely Benign9
Benign1
19
Pathogenic
2
Likely Pathogenic
86
VUS
9
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
2
0
2
VUS
0
81
5
0
86
Likely Benign
0
7
1
1
9
Benign
0
1
0
0
1
Total089271117

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

View in ClinVar →

Protein Context — Lollipop Plot

ZCWPW1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease.
Holstege H et al.·Nat Genet
2022
A loss-of-function variant in ZCWPW1 causes human male infertility with sperm head defect and high DNA fragmentation.
Song Y et al.·Reprod Health
2024
ZCWPW1 is associated with late-onset Alzheimer's disease in Han Chinese: a replication study and meta-analyses.
Gao Y et al.·Oncotarget
2016Meta-analysis
Genetics of Alzheimer's disease.
Chouraki V et al.·Adv Genet
2014Review
Connecting dementia risk loci to the CSF proteome identifies pathophysiological leads for dementia.
Reus LM et al.·Brain
2024
Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer's Disease.
Angelopoulou E et al.·Int J Mol Sci
2024Review
Genetic Comparison of Symptomatic and Asymptomatic Persons With Alzheimer Disease Neuropathology.
Monsell SE et al.·Alzheimer Dis Assoc Disord
2017
Whole-exome sequencing of the BDR cohort: evidence to support the role of the PILRA gene in Alzheimer's disease.
Patel T et al.·Neuropathol Appl Neurobiol
2018Cohort
Relation of genomic variants for Alzheimer disease dementia to common neuropathologies.
Farfel JM et al.·Neurology
2016
Alzheimer disease (AD) specific transcription, DNA methylation and splicing in twenty AD associated loci.
Humphries C et al.·Mol Cell Neurosci
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools