ZIC1 Gene - Zinc Finger Protein of the Cerebellum 1
Key regulator of neural development and associated with Dandy-Walker malformation
Gene Information Card
| Symbol | ZIC1 |
|---|---|
| Full Name | Zic family member 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 3q24 |
| NCBI Gene ID | 7545 ncbi.nlm.nih.gov/gene/7545 |
| Ensembl ID | ENSG00000152977 |
| UniProt ID | Q15915 |
| OMIM ID | 600470 |
| HGNC ID | 12872 |
| Aliases | ZIC, ZNF201, DWM1 |
Description
ZIC1 encodes a zinc finger transcription factor belonging to the ZIC family of C2H2-type zinc finger proteins. It plays a critical role in early neural development, particularly in the patterning of the cerebellum and dorsal neural tube. ZIC1 is expressed predominantly in the developing and adult cerebellum and is involved in cell proliferation, differentiation, and migration. Mutations in ZIC1 are associated with Dandy-Walker malformation and other craniofacial anomalies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dandy-Walker malformation | Loss-of-function mutations in ZIC1 disrupt cerebellar development leading to posterior fossa malformation | ClinVar, OMIM #600470 |
| Craniofacial anomalies | ZIC1 haploinsufficiency affects neural crest cell migration and craniofacial patterning | OMIM, PubMed |
| Holoprosencephaly-like phenotype | ZIC1 mutations impair forebrain midline development | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebellum | 45.2 | High |
| Cerebral cortex | 12.8 | Medium |
| Fetal brain | 18.5 | Medium |
| Spinal cord | 8.3 | Low |
| Testis | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 22.4 | Neuronal lineage |
| U-87 MG (glioblastoma) | 15.7 | Glial lineage |
| HEK293 (embryonic kidney) | 1.2 | Low expression |
| HepG2 (hepatocellular carcinoma) | 0.8 | Not expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335Ter) | Nonsense | Rare | Loss of function; truncation of zinc finger domain |
| c.1246G>A (p.Gly416Arg) | Missense | Rare | Loss of function; impaired DNA binding |
| c.1462delC (p.Leu488TrpfsTer12) | Frameshift | Rare | Loss of function; premature termination |
Mutation functional classification
Loss of Function (LOF)
Most ZIC1 mutations associated with Dandy-Walker malformation are loss-of-function, leading to haploinsufficiency.
Gain of Function (GOF)
No gain-of-function mutations reported in ZIC1.
Dominant Negative (DN)
Dominant-negative effects have not been described for ZIC1 mutations.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hedgehog signaling pathway (Reactome: R-HSA-5358351)
• Neural crest differentiation (WikiPathways: WP2064)
• Developmental biology (Reactome: R-HSA-1266738)
Protein Summary
ZIC1 is a 447-amino acid protein containing five C2H2-type zinc finger domains that mediate sequence-specific DNA binding. It functions as a transcriptional repressor or activator depending on context, regulating genes involved in cerebellar and neural crest development. The protein localizes to the nucleus and interacts with other transcription factors such as GLI proteins to modulate Hedgehog signaling. ZIC1 is highly conserved across vertebrates.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZIC1 Knockout HEK293 Cell Line | EDJ-KQ2768 | Human | 7545 | Details Get a Quote |
| ZIC1 Knockout HeLa Cell Line | EDJ-KQ54764 | Human | 7545 | Details Get a Quote |
| ZIC1 Knockout A-549 Cell Line | EDJ-KQ63257 | Human | 7545 | Details Get a Quote |
| ZIC1 Knockout HCT 116 Cell Line | EDJ-KQ71722 | Human | 7545 | Details Get a Quote |
