ZIC2
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
ZIC2 (HGNC:12873) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
Zic family member 2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
HPE5
%HI
6.3(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.96(Read more about gnomAD pLI score)
LOEUF
0.52(Read more about gnomAD LOEUF score)
Cytoband
13q32.3
Genomic Coordinates
GRCh37/hg19: chr13:100634038-100639019 NCBI Ensembl UCSC
GRCh38/hg38: chr13:99981784-99986765 NCBI Ensembl UCSC
MANE Select Transcript
NM_007129.5 ENST00000376335.8 (Read more about MANE Select)
Function
Acts as a transcriptional activator or repressor. Plays important roles in the early stage of organogenesis of the CNS. Activates the transcription of the serotonin transporter SERT in uncrossed ipsilateral retinal ganglion cells (iRGCs) to refine eye- specific projections in primary visual targets. Its transcriptional activity is repressed by MDFIC. Involved in the formation of the ipsilateral retinal projection at the optic chiasm midline. Drives the expression of EPHB1 on ipsilaterally projec... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-2954
ClinGen Curation ID:
CCID:008135
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
08/24/2022

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 19955556
    A comprehensive, multi-center study by Solomon et al (2010) identified 103 probands presenting with holoprosencephaly who harbored ZIC2 gene variants. Of the 103 probands identified in the study, 29 unrelated probands harbored a de novo nonsense variant (probands n=9; patients: 6, 7, 10, 18, 26, 27, 42, 60; Table 2) or a de novo frameshift variant (probands n=20, patients: 1, 2, 5, 8, 12, 21, 22, 29, 37, 43, 50, 51, 52, 55, 61a-proband, 61b-twin, 64, 76, 98, 99, 102; Table 2) all predicted to be loss-of-function.
  • PUBMED: 28640243
    Weiss et al (2018) identified three unrelated individuals presenting with semilobar holoprosencephaly who harbored a de novo pathogenic variant in ZIC2 identified through whole exome sequencing. Two of the individuals harbored a nonsense variant (subject 13: c.1095_1096del, p.Cys365*; subject 20: c.793C >T, p.Gln265*) while the third individual harbored a frameshift variant (subject 16: c.1148_1464del, p.Ser482Argfs*42).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
PMID 22105922: Jobanputra et al (2012) identified a 564 kb duplication including ZIC2 (and 3 other genes) as part of a complex chromosomal rearrangement in a fetus referred for prenatal counseling. The fetus was born without holoprosencephaly and showed normal development at age 3 months. After review of phenotypes of 7 additional patients with large (>18 Mb) gains of 13q containing ZIC2, the authors concluded that duplication of ZIC2 is not associated with holoprosencephaly.

Genomic View

Select assembly: (NC_000013.10) (NC_000013.11)