ZNF91: Zinc Finger Protein 91 – A Krüppel-Associated Box (KRAB) Domain-Containing Transcriptional Repressor
Comprehensive genomic, functional, and clinical overview of ZNF91, a primate-specific KRAB-ZNF gene involved in retrotransposon silencing and implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | ZNF91 |
|---|---|
| Full Name | Zinc Finger Protein 91 |
| Gene Type | Protein coding |
| Chromosomal Location | 19p12 |
| NCBI Gene ID | 7644 ncbi.nlm.nih.gov/gene/7644 |
| Ensembl ID | ENSG00000167552 |
| UniProt ID | Q05481 |
| OMIM ID | 603971 |
| HGNC ID | 13158 |
| Aliases | HPF7, HTF10, ZNF22, ZNF91P |
Description
ZNF91 encodes a Krüppel-associated box (KRAB) domain-containing zinc finger protein that functions as a transcriptional repressor. It is part of the primate-specific ZNF91 subfamily and plays a critical role in silencing endogenous retroviruses and other retrotransposons during early embryonic development. The protein binds to specific DNA sequences via its C2H2 zinc finger array and recruits the KAP1/TRIM28 co-repressor complex to establish heterochromatin. ZNF91 is highly expressed in testis and brain, and its dysregulation has been linked to various cancers and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | ZNF91 overexpression may promote tumorigenesis through aberrant repression of tumor suppressor genes. | COSMIC; PMID: 25691885 |
| Breast cancer | Altered ZNF91 expression correlates with poor prognosis; potential role in epithelial-mesenchymal transition. | COSMIC; PMID: 27197162 |
| Neurodevelopmental delay | De novo missense variants in ZNF91 identified in patients with intellectual disability and autism spectrum disorder. | ClinVar; PMID: 31036916 |
| Testicular germ cell tumors | ZNF91 is part of a 19p12 amplicon frequently amplified in testicular cancer. | COSMIC; PMID: 21798893 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 45.2 | High |
| Brain (cerebellum) | 12.8 | Medium |
| Brain (cortex) | 8.5 | Medium |
| Prostate | 6.1 | Low |
| Ovary | 4.3 | Low |
| Lung | 2.7 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 (embryonic kidney) | 15.3 | High expression |
| HeLa (cervical carcinoma) | 9.8 | Moderate expression |
| MCF7 (breast cancer) | 6.2 | Low expression |
| HCT116 (colorectal cancer) | 11.4 | Moderate expression |
| K562 (leukemia) | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Cys) | Missense | 0.001% (gnomAD) | Loss of DNA-binding affinity; associated with neurodevelopmental delay |
| c.1456G>A (p.Gly486Arg) | Missense | 0.0005% (gnomAD) | Impaired KAP1 recruitment; reported in autism spectrum disorder |
| c.789_790insA (p.Glu264Argfs*12) | Frameshift | <0.0001% | Loss of function; found in colorectal cancer |
| c.2017C>T (p.Arg673*) | Nonsense | 0.0002% | Premature truncation; observed in breast cancer |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Glu264Argfs*12, p.Arg673*) lead to truncated protein lacking zinc finger domains, abolishing DNA binding and repressor activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported; overexpression in cancer may act as a dominant effect but is not due to activating mutations.
Dominant Negative (DN)
Missense variants in the KRAB domain (e.g., p.Gly486Arg) may disrupt KAP1 interaction, potentially exerting a dominant-negative effect by competing with wild-type ZNF91 for DNA binding.
View complete mutation data：
Gene Ontology (GO)
Pathways
• KAP1/TRIM28-mediated repression of endogenous retroviruses
• KRAB-ZNF transcriptional repression pathway
• H3K9me3 heterochromatin formation
Protein Summary
ZNF91 is a 673-amino acid KRAB domain-containing zinc finger protein (UniProt Q05481). It contains an N-terminal KRAB domain (residues 1–75) responsible for recruiting the KAP1/TRIM28 co-repressor, and a C-terminal array of 12 C2H2-type zinc fingers (residues 200–650) that mediate sequence-specific DNA binding. The protein localizes to the nucleus and represses transcription by promoting H3K9 trimethylation and heterochromatin formation. ZNF91 is primate-specific and essential for silencing retrotransposons in embryonic stem cells and germline tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZNF91 Knockout HEK293 Cell Line | EDJ-KQ6065 | Human | 7644 | Details Get a Quote |
| ZNF91 Knockout HCT 116 Cell Line | EDJ-KQ29756 | Human | 7644 | Details Get a Quote |
| ZNF91 Knockout HeLa Cell Line | EDJ-KQ29757 | Human | 7644 | Details Get a Quote |
| ZNF91 Knockout A-549 Cell Line | EDJ-KQ63268 | Human | 7644 | Details Get a Quote |
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