ZIC1
Zic family member 1, the group of Zinc fingers C2H2-type
Basic information
Region (hg38): 3:147393422-147510293
Links
Phenotypes
GenCC
Source:
- craniosynostosis 6 (Definitive), mode of inheritance: AD
- structural brain anomalies with impaired intellectual development and craniosynostosis (Strong), mode of inheritance: AD
- craniosynostosis 6 (Strong), mode of inheritance: AD
- craniosynostosis 6 (Moderate), mode of inheritance: AD
- isolated plagiocephaly (Supportive), mode of inheritance: AD
- isolated brachycephaly (Supportive), mode of inheritance: AD
- isolated oxycephaly (Supportive), mode of inheritance: AD
- Dandy-Walker syndrome (Limited), mode of inheritance: AD
- craniosynostosis 6 (Strong), mode of inheritance: AD
- structural brain anomalies with impaired intellectual development and craniosynostosis (Limited), mode of inheritance: Unknown
- craniosynostosis 6 (Definitive), mode of inheritance: AD
- structural brain anomalies with impaired intellectual development and craniosynostosis (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Craniosynostosis 6; Structural brain anomalies with impaired intellectual development and craniosynostosis | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Neurologic | 26340333; 30391508 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (143 variants)
- Inborn_genetic_diseases (22 variants)
- ZIC1-related_disorder (9 variants)
- Structural_brain_anomalies_with_impaired_intellectual_development_and_craniosynostosis (8 variants)
- not_specified (6 variants)
- Craniosynostosis_6 (3 variants)
- See_cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZIC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003412.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 49 | 56 | ||||
| missense | 77 | 95 | ||||
| nonsense | 8 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 5 | 8 | 81 | 57 | 11 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ZIC1 | protein_coding | protein_coding | ENST00000282928 | 3 | 116872 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.934 | 0.0662 | 123380 | 0 | 1 | 123381 | 0.00000405 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.57 | 160 | 281 | 0.569 | 0.0000127 | 2935 |
| Missense in Polyphen | 57 | 128.05 | 0.44512 | 1389 | ||
| Synonymous | -2.81 | 161 | 122 | 1.32 | 0.00000596 | 889 |
| Loss of Function | 3.09 | 1 | 13.0 | 0.0767 | 5.65e-7 | 138 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000291 | 0.0000291 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Acts as a transcriptional activator. Involved in neurogenesis. Plays important roles in the early stage of organogenesis of the CNS, as well as during dorsal spinal cord development and maturation of the cerebellum. Involved in the spatial distribution of mossy fiber (MF) neurons within the pontine gray nucleus (PGN). Plays a role in the regulation of MF axon pathway choice. Promotes MF migration towards ipsilaterally- located cerebellar territories. May have a role in shear flow mechanotransduction in osteocytes. Retains nuclear GLI1 and GLI3 in the cytoplasm. Binds to the minimal GLI-consensus sequence 5'- TGGGTGGTC-3' (By similarity). {ECO:0000250|UniProtKB:P46684}.;
- Disease
- DISEASE: Craniosynostosis 6 (CRS6) [MIM:616602]: A form of craniosynostosis, a primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability. {ECO:0000269|PubMed:26340333}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Neural Crest Differentiation;Differentiation of white and brown adipocyte
(Consensus)
Recessive Scores
- pRec
- 0.281
Intolerance Scores
- loftool
- 0.0318
- rvis_EVS
- -0.49
- rvis_percentile_EVS
- 22.09
Haploinsufficiency Scores
- pHI
- 0.822
- hipred
- Y
- hipred_score
- 0.837
- ghis
- 0.716
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.995
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Zic1
- Phenotype
- muscle phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Zebrafish Information Network
- Gene name
- zic1
- Affected structure
- optic fissure
- Phenotype tag
- abnormal
- Phenotype quality
- closure incomplete
Gene ontology
- Biological process
- pattern specification process;central nervous system development;brain development;adult walking behavior;regulation of smoothened signaling pathway;spinal cord development;cell differentiation;positive regulation of protein import into nucleus;inner ear morphogenesis;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
- Cellular component
- nucleus;cytoplasm
- Molecular function
- RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;metal ion binding