ZBTB34

Chr 9

zinc finger and BTB domain containing 34

Also known as: ZNF918

The protein functions as a transcriptional repressor that binds DNA and negatively regulates RNA polymerase II transcription, with additional roles in regulating cytokine production and immune system processes. Loss-of-function mutations in ZBTB34 cause disease through haploinsufficiency, as evidenced by the high pLI score (0.98) and low LOEUF score (0.30) indicating strong intolerance to heterozygous loss-of-function variants. The specific disease phenotype and inheritance pattern associated with ZBTB34 mutations have not been established in the provided information.

OMIMResearchSummary from RefSeq, UniProt, Mechanism
LOFmechanismLOEUF 0.30
Clinical SummaryZBTB34
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 55 VUS of 101 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.977
Z-score 3.47
OE 0.06 (0.020.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.81Z-score
OE missense 0.55 (0.480.62)
168 obs / 306.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.06 (0.020.30)
00.351.4
Missense OE0.55 (0.480.62)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 1 / 15.9Missense obs/exp: 168 / 306.6Syn Z: -0.51
DN
0.3097th %ile
GOF
0.2696th %ile
LOF
0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.30

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

101 submitted variants in ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic1
VUS55
34
Pathogenic
1
Likely Pathogenic
55
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
34
0
34
Likely Pathogenic
0
0
1
0
1
VUS
1
53
1
0
55
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total15336090

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

View in ClinVar →

Protein Context — Lollipop Plot

ZBTB34 · 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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