ZRANB3: Zinc Finger RANBP2-Type Containing 3
A DNA structure-specific endonuclease involved in replication fork stability and DNA repair
Gene Information Card
| Symbol | ZRANB3 |
|---|---|
| Full Name | Zinc Finger RANBP2-Type Containing 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q21.2 |
| NCBI Gene ID | 84083 ncbi.nlm.nih.gov/gene/84083 |
| Ensembl ID | ENSG00000162944 |
| UniProt ID | Q5FWF6 |
| OMIM ID | 615655 |
| HGNC ID | 25282 |
| Aliases | AH2, C2orf60, FLJ12874, ZRANB3 |
Description
ZRANB3 encodes a DNA structure-specific endonuclease that belongs to the SNM1 family of nucleases. The protein contains a zinc finger RANBP2-type domain and a UvrD-like helicase domain. It plays a key role in replication fork stabilization and restart during DNA replication stress, as well as in interstrand crosslink repair. ZRANB3 is recruited to stalled replication forks via PCNA polyubiquitination and cleaves branched DNA structures, facilitating fork regression and restart.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Fanconi anemia complementation group (potential) | Defective interstrand crosslink repair due to loss of ZRANB3 endonuclease activity | Inferred from functional studies and pathway analysis (OMIM 615655) |
| Cancer (various) | Genomic instability from impaired replication fork restart and DNA repair | COSMIC mutation data; somatic mutations in multiple tumor types |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Bone marrow | 8.2 | Low |
| Lymph node | 6.1 | Low |
| Brain | 4.3 | Low |
| Liver | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Embryonic kidney; moderate expression |
| HeLa | 7.5 | Cervical carcinoma; low-moderate |
| K562 | 6.8 | Leukemia; low |
| HepG2 | 5.2 | Hepatocellular carcinoma; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.01% | Loss of function; truncated protein |
| c.567G>A (p.Trp189*) | Nonsense | <0.01% | Loss of function; premature stop |
| c.890A>G (p.Tyr297Cys) | Missense | <0.01% | Unknown; possibly damaging (ClinVar) |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated or absent protein impair endonuclease activity and replication fork restart.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Fanconi anemia pathway (Reactome R-HSA-6783310)
• Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template (Reactome R-HSA-110313)
• Resolution of D-loop structures through Holliday junction intermediates (Reactome R-HSA-5693571)
Protein Summary
ZRANB3 is a 1070-amino acid protein with a molecular weight of approximately 120 kDa. It contains an N-terminal UvrD-like helicase domain, a central zinc finger RANBP2-type domain, and a C-terminal SNM1-like nuclease domain. The protein localizes to the nucleus and is recruited to sites of DNA damage. It exhibits both endonuclease and 3'-5' helicase activities, enabling it to process stalled replication forks and promote fork restart. ZRANB3 interacts with PCNA and is regulated by ubiquitination.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZRANB3 Knockout HEK293 Cell Line | EDJ-KQ9976 | Human | 84083 | Details Get a Quote |
| ZRANB3 Knockout A-549 Cell Line | EDJ-KQ35710 | Human | 84083 | Details Get a Quote |
| ZRANB3 Knockout HCT 116 Cell Line | EDJ-KQ36914 | Human | 84083 | Details Get a Quote |
| ZRANB3 Knockout HeLa Cell Line | EDJ-KQ36915 | Human | 84083 | Details Get a Quote |
