ZNF84: Zinc Finger Protein 84 – A Krüppel-Associated Box (KRAB) Domain-Containing Transcriptional Regulator

Comprehensive biomedical overview of ZNF84, including genomic context, expression, and disease associations.

Gene Information Card

Symbol ZNF84
Full Name zinc finger protein 84
Gene Type protein-coding
Chromosomal Location 12q24.33
NCBI Gene ID 7840 ncbi.nlm.nih.gov/gene/7840
Ensembl ID ENSG00000198042
UniProt ID P51523
OMIM ID 603975
HGNC ID 13156
Aliases HPF2, ZNF-84, ZNF84A

Description

ZNF84 encodes a zinc finger protein of the Krüppel-associated box (KRAB) family. The protein contains a KRAB domain at the N-terminus and multiple C2H2-type zinc finger motifs, characteristic of transcriptional repressors. ZNF84 is involved in chromatin regulation and gene silencing, and is expressed in various tissues. Its precise biological roles are under investigation, with emerging links to cancer and developmental processes.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Breast cancer Altered expression; potential role in transcriptional dysregulation COSMIC; literature (PMID: 25691885)
Colorectal cancer Somatic mutations and copy number alterations observed COSMIC; TCGA
Prostate cancer Expression changes associated with tumor progression COSMIC; literature (PMID: 28723887)

Expression Profile

Tissue Expression
Tissue nTPM level
Testis 10.2 Medium
Brain 5.8 Low
Lung 4.1 Low
Liver 3.5 Low
Kidney 4.9 Low
Cell Line Expression
Cell Line nTPM Notes
HEK293 8.7 Moderate expression
HeLa 6.2 Low expression
K562 5.0 Low expression
MCF7 7.1 Moderate expression
Data source：Human Protein Atlas（proteinatlas.org）

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.1015C>T (p.Arg339Cys) Missense <0.01% Unknown functional impact; rare population variant
c.1234G>A (p.Gly412Ser) Missense <0.01% Reported in COSMIC; uncertain significance
c.1450_1451insA Frameshift <0.01% Predicted loss-of-function
Mutation functional classification

Loss of Function (LOF)

Frameshift and nonsense variants likely lead to truncated protein lacking zinc finger domains, impairing DNA binding.

Gain of Function (GOF)

No confirmed gain-of-function mutations reported.

Dominant Negative (DN)

Not established; potential if mutant protein interferes with wild-type function via dimerization.
View complete mutation data：
ClinVar：https://www.clinvar.com/gene/7840
COSMIC：https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=ZNF84

Gene Ontology (GO)

• DNA binding (GO:0003677) • RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978)
• DNA-binding transcription factor activity (GO:0000981) • nucleus (GO:0005634)
• regulation of transcription by RNA polymerase II (GO:0006357) • metal ion binding (GO:0046872)

Pathways

• No specific curated pathways; predicted involvement in transcriptional repression via KRAB domain interaction with KAP1/TRIM28.

Protein Summary

ZNF84 is a 647-amino acid protein containing a KRAB domain and 14 C2H2 zinc fingers. It localizes to the nucleus and functions as a sequence-specific DNA-binding transcriptional repressor. The KRAB domain mediates recruitment of the KAP1 corepressor complex, leading to histone modifications and chromatin compaction. Expression is detected in multiple tissues, with highest levels in testis. Mutations are rare but have been identified in cancer genomes, though functional consequences remain largely uncharacterized.

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Displaying Records 1 To 15 Of 24 Records

Reference Databases

NCBI Gene https://www.ncbi.nlm.nih.gov/gene/7840
OMIM https://www.omim.org/entry/603975
HGNC https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13156
Ensembl https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000198042
UniProt https://www.uniprot.org/uniprot/P51523
ClinVar https://www.ncbi.nlm.nih.gov/clinvar/?term=ZNF84%5Bgene%5D
COSMIC https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=ZNF84
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