ZIC4
  • 0
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
ZIC4 (HGNC:20393) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
Zic family member 4
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
No aliases found
%HI
12.76(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.01(Read more about gnomAD pLI score)
LOEUF
0.83(Read more about gnomAD LOEUF score)
Cytoband
3q24
Genomic Coordinates
GRCh37/hg19: chr3:147103833-147124330 NCBI Ensembl UCSC
GRCh38/hg38: chr3:147386046-147406543 NCBI Ensembl UCSC
MANE Select Transcript
NM_032153.6 ENST00000383075.8 (Read more about MANE Select)
Function
Binds to DNA. {ECO:0000250}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-30312
ClinGen Curation ID:
CCID:008137
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
No Evidence for Haploinsufficiency (0)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Related Links:
Last Evaluated:
08/25/2021

Haploinsufficiency (HI) Score Details

HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency (Disclaimer)
HI Evidence Comments:
As all reported deletions involving ZIC4 include its closely linked homolog ZIC1, the clinical consequence of haploinsufficiency for ZIC4 alone is not known. PMID 15338008: Grinberg et al. (2004) describes seven individuals who presented with Dandy-Walker malformation and substantial cognitive deficits. Each of the individuals was found to have a de novo interstitial deletion of the long arm of chromosome 3 (3q). Through metaphase FISH analysis using BAC clones a 1.9-Mb critical region was identified which encompasses 13 genes, one of which is ZIC4. PMID 21204220: Tohyama et al. (2011) describes an individual presenting with developmental delay, epilepsy, and multiple congenital malformations including spina bifida, mild dysmorphic facial features including, thick eyebrows, broad nose, full lips, macroglossia, and hypoplasia of the cerebellar vermis with enlargement of the fourth ventricle on brain magnetic resonance imaging, which is consistent with Dandy–Walker malformation. Chromosome analysis showed an interstitial deletion of the long arm of chromosome 3 [del(3)(q23q25.1)]. FISH analysis and microarray identified a de novo 14-Mb deletion [chr 3: 142,479,100-156,504,521] which includes 67 genes, one of which is ZIC4. The deletion was not observed in the proband’s neurotypical presenting brother or parents. PMID 21471554: Lim et al. (2011) describes an individual presenting with blepharophimosis/ptosis/epicanthus inversus syndrome, Dandy-Walker malformation, and global developmental delay. Chromosome analysis identified a deletion of the long arm of chromosome 3 (3q) [del(3)(q22.3q25.2)]. Micorarray identified a de novo 14.92-Mb interstitial deletion [chr 3:139,328,000-154,254,416] which includes 82 genes, one of which is ZIC4. The deletion was not observed in the proband’s neurotypical presenting twin brother or parents. PMID 23679990: Ferraris et al. (2013) describes three individuals presenting with global developmental delay, multiple congenital anomalies, and peculiar facial appearance. Phenotypes resulted from the variable combination of three recognizable patterns: Dandy-Walker malformation, blepharophimosis, ptosis, and epicanthus inversus syndrome, and Wisconsin syndrome. Microarry identified overlapping deletions (4.9, 20, and 20-Mb) of the long arm of chromosome 3 with the common deleted region including ZIC4 and various other genes. PMID 28503614: Ramineni and Coman (2016) describes an individual presenting with blepharophimosis–ptosis–epicanthus inversus syndrome, Dandy-Walker malformation, and Wisconsin syndrome. Microarray identified a de novo 12-Mb interstitial deletion [chr 3: 136,403,035-148,341,113] which includes 60 genes, one of which is ZIC4. Other notable cases with similar clinical presentations and genomic findings: PMID 23313878, 16179233, 20215058, 21204216. For more information on the larger region including ZIC4, please see the review of the 3q24 region (ISCA-46553).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Full gene duplication of only ZIC4 has not been reported in the literature at the time of review.

Genomic View

Select assembly: (NC_000003.11) (NC_000003.12)