• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
ZIC3 (HGNC:12874) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
Zic family member 3
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
HTX1
Alias symbols
HTX, ZNF203
%HI
4.79(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.92(Read more about gnomAD pLI score)
LOEUF
0.36(Read more about gnomAD LOEUF score)
Cytoband
Xq26.3
Genomic Coordinates
GRCh37/hg19: chrX:136648286-136659850 NCBI Ensembl UCSC
GRCh38/hg38: chrX:137566127-137577691 NCBI Ensembl UCSC
MANE Select Transcript
NM_003413.4 ENST00000287538.10 (Read more about MANE Select)
Function
Acts as a transcriptional activator. Required in the earliest stages in both axial midline development and left-right (LR) asymmetry specification. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC- 3'. {ECO:0000269|PubMed:17764085}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-1281
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
12/02/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • heterotaxy, visceral, 1, X-linked Monarch
HI Evidence:
  • PUBMED: 27821535
    Cowan (2016) reviewed CNVs in 225 pts with heterotaxy and heterotaxy-spectrum congenital heart defects. Reported male patient with heterotaxy with an assumed de novo 2.9-3.33 kb deletion including the third exon of ZIC3.
  • PUBMED: 24123890
    Cowan 2014 report ZIC3 sequencing variants from 440 unrelated pts with heterotaxy and congenital heart disease. 11 variants found among 15 patients, 8 of which were novel. 4 inherited, 10 assumed de novo, 1 unknown inheritance. Two of the variants were nonsense, one an assumed de novo in a male with heterotaxy. The other nonsense variant was found inherited from an unaffected carrier mother in a female with congenital heart anomalies who was sequenced rather than her affected son with heterotaxy. Functional studies demonstrated decreased gene transactivation and abnormal subcellular localization and supported loss of function mechanism of disease.
  • PUBMED: 14681828
    Ware (2004): Report of two families with X-linked classic heterotaxy due to nonsense mutations resulting in lack of protein. All affected individuals were male and female carriers were normal. Clinical features were variable and included cardiac-related heterotaxy and additional visceral anomalies.
HI Evidence Comments:
Several additional publications report nonsense and other disruptive variants associated with heterotaxy and congenital heart defects: 9354794, 21465648, 30622330, 30120289, 22171628, 27406248, 23427188.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)