ZKSCAN3

Chr 6

zinc finger with KRAB and SCAN domains 3

Also known as: ZF47, ZFP306, ZNF306, ZNF309, ZSCAN13, ZSCAN35, Zfp47, dJ874C20.1

NCBI Gene: 80317ENSG00000189298UniProt: Q9BRR0

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and chromatin binding activity. Involved in several processes, including negative regulation of autophagy; negative regulation of cellular senescence; and regulation of DNA-templated transcription. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

59
ClinVar variants
5
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ZKSCAN3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 51 VUS of 59 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.
1.19LOEUF
pLI 0.000
Z-score 0.84
OE 0.81 (0.56–1.19)
Tolerant

Highly tolerant — LoF variants common in population

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.
1.64Z-score
OE missense 0.73 (0.65–0.82)
212 obs / 290.6 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.0.81 (0.56–1.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.65–0.82)
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.0.87
0≤1.21.6
LoF obs/exp: 19 / 23.4Missense obs/exp: 212 / 290.6Syn Z: 1.11

ClinVar Variant Classifications

59 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS51
Likely Benign3
4
Pathogenic
1
Likely Pathogenic
51
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
0
49
2
0
51
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total0527059

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

View in ClinVar →

Protein Context — Lollipop Plot

ZKSCAN3 · 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
Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration.
Rusmini P et al.·Autophagy
2019Functional
LRRK2 is required for CD38-mediated NAADP-Ca(2+) signaling and the downstream activation of TFEB (transcription factor EB) in immune cells.
Nabar NR et al.·Autophagy
2022
The Biological Roles of ZKSCAN3 (ZNF306) in the Hallmarks of Cancer: From Mechanisms to Therapeutics.
Li W et al.·Int J Mol Sci
2024Review
ZKSCAN3 Upregulation and Its Poor Clinical Outcome in Uterine Cervical Cancer.
Lee S et al.·Int J Mol Sci
2018
Unveiling novel potential drug targets for lung cancer through Mendelian randomization analysis.
Huang Y et al.·Sci Rep
2025
KRAB-ZFP Transcriptional Regulators Acting as Oncogenes and Tumor Suppressors: An Overview.
Sobocińska J et al.·Int J Mol Sci
2021Review
Shared Genetic Basis and Causality Between Epilepsy and Psychiatric Disorders: Evidence From a Comprehensive Genetic Analysis.
Feng X et al.·Brain Behav
2026
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