ZBED4

Chr 22

zinc finger BED-type containing 4

NCBI Gene: 9889ENSG00000100426UniProt: O75132

Enables identical protein binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

333
ClinVar variants
138
Pathogenic / LP
0.51
pLI score
0
Active trials
Clinical Summary— ZBED4
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.51) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
138 Pathogenic / Likely Pathogenic· 164 VUS of 333 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.41LOEUF
pLI 0.507
Z-score 4.14
OE 0.22 (0.12–0.41)
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.
2.26Z-score
OE missense 0.77 (0.71–0.82)
560 obs / 732.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.22 (0.12–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.71–0.82)
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.1.12
0≤1.21.6
LoF obs/exp: 7 / 32.5Missense obs/exp: 560 / 732.0Syn Z: -1.78

ClinVar Variant Classifications

333 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic136
Likely Pathogenic2
VUS164
Likely Benign16
Benign7
136
Pathogenic
2
Likely Pathogenic
164
VUS
16
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
136
0
136
Likely Pathogenic
0
0
2
0
2
VUS
0
156
8
0
164
Likely Benign
0
15
0
1
16
Benign
0
1
1
5
7
Total01721476325

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

View in ClinVar →

Protein Context — Lollipop Plot

ZBED4 · 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
Sequence-specific binding of recombinant Zbed4 to DNA: insights into Zbed4 participation in gene transcription and its association with other proteins.
Mokhonov VV et al.·PLoS One
2012
No association of BRD1 and ZBED4 polymorphisms with schizophrenia in the Chinese Han population.
Xu F et al.·Psychiatr Genet
2018
ZBED4, a novel retinal protein expressed in cones and Müller cells.
Farber DB et al.·Adv Exp Med Biol
2010
ZBED4, a BED-type zinc-finger protein in the cones of the human retina.
Saghizadeh M et al.·Invest Ophthalmol Vis Sci
2009
ZBED4, a cone and Müller cell protein in human retina, has a different cellular expression in mouse.
Saghizadeh M et al.·Mol Vis
2011Functional
Support of association between BRD1 and both schizophrenia and bipolar affective disorder.
Nyegaard M et al.·Am J Med Genet B Neuropsychiatr Genet
2010Meta-analysis
Human DNA replication-related element binding factor (hDREF) self-association via hATC domain is necessary for its nuclear accumulation and DNA binding.
Yamashita D et al.·J Biol Chem
2007
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
ZBED4: A Prognostic Biomarker and Therapeutic Target in Hepatocellular Carcinoma.
Ding J et al.·J Hepatocell Carcinoma
2025🔓 Open Access
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