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)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
08/24/2022
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- holoprosencephaly Monarch
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)