ZKSCAN3: Zinc Finger Protein with KRAB and SCAN Domains 3

Transcriptional regulator involved in autophagy, cell proliferation, and cancer

Gene Information Card

Symbol ZKSCAN3
Full Name Zinc Finger Protein With KRAB And SCAN Domains 3
Gene Type Protein coding
Chromosomal Location 6p22.1
NCBI Gene ID 29993 ncbi.nlm.nih.gov/gene/29993
Ensembl ID ENSG00000118526
UniProt ID Q9BRR0
OMIM ID 617521
HGNC ID 13099
Aliases ZNF306, ZSCAN37, ZKSCAN3

Description

ZKSCAN3 (Zinc Finger Protein With KRAB And SCAN Domains 3) is a transcription factor that represses autophagy and lysosome biogenesis. It contains a KRAB domain and multiple C2H2-type zinc fingers. ZKSCAN3 is implicated in various cancers, including colorectal, prostate, and breast cancer, where it often acts as an oncogene by promoting cell proliferation and inhibiting autophagy.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Colorectal Cancer Overexpression of ZKSCAN3 represses autophagy and promotes tumor growth; knockdown induces autophagic cell death PMID: 23563491, COSMIC
Prostate Cancer ZKSCAN3 upregulation correlates with poor prognosis; promotes proliferation and invasion PMID: 28249903
Breast Cancer ZKSCAN3 overexpression associated with aggressive subtypes; regulates cell cycle and autophagy PMID: 30598549
Multiple Myeloma ZKSCAN3 is a target of the miR-137 tumor suppressor; silencing reduces cell viability PMID: 26921324

Expression Profile

Tissue Expression
Tissue nTPM level
Testis 12.5 Medium
Bone Marrow 8.2 Low
Colon 6.1 Low
Prostate 5.8 Low
Breast 4.3 Low
Cell Line Expression
Cell Line nTPM Notes
HeLa 15.2 Cervical cancer cell line
HCT116 12.8 Colorectal carcinoma cell line
MCF7 9.5 Breast cancer cell line
PC3 8.7 Prostate cancer cell line
K562 6.3 Leukemia cell line
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.1015C>T (p.Arg339Trp) Missense <0.01% Unknown; rare variant in COSMIC
c.1246G>A (p.Gly416Arg) Missense <0.01% Unknown; rare variant in COSMIC
c.1570_1571insA (p.Thr524Asnfs*2) Frameshift <0.01% Predicted loss of function
Mutation functional classification

Loss of Function (LOF)

Frameshift mutations (e.g., p.Thr524Asnfs*2) likely result in truncated protein lacking zinc fingers, leading to loss of transcriptional repression.

Gain of Function (GOF)

Not well documented; overexpression in cancer suggests potential gain-of-function via increased repressive activity on autophagy genes.

Dominant Negative (DN)

No evidence for dominant-negative effects currently reported.

Pathways

• Autophagy – ZKSCAN3 represses autophagy-related genes (e.g.
• MAP1LC3B
• ULK1)
• Lysosome biogenesis – ZKSCAN3 inhibits TFEB target genes
• Cell cycle – ZKSCAN3 promotes G1/S transition via cyclin D1 regulation

Protein Summary

ZKSCAN3 is a 544-amino acid nuclear protein containing an N-terminal KRAB domain, a SCAN domain, and 11 C2H2-type zinc fingers. It functions as a transcriptional repressor by binding to specific DNA sequences and recruiting corepressor complexes. ZKSCAN3 negatively regulates autophagy and lysosome biogenesis, thereby promoting cell survival and proliferation. Its overexpression in multiple cancers suggests an oncogenic role.

Related Products

Product name Cat.No. Species Gene ID
ZKSCAN3 Knockout HEK293 Cell Line EDJ-KQ3193 Human 80317 Details Get a Quote
ZKSCAN3 Knockout A-549 Cell Line EDJ-KQ24642 Human 80317 Details Get a Quote
ZKSCAN3 Knockout HCT 116 Cell Line EDJ-KQ24643 Human 80317 Details Get a Quote
ZKSCAN3 Knockout HeLa Cell Line EDJ-KQ24644 Human 80317 Details Get a Quote
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