• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
GLI2 (HGNC:4318) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
GLI family zinc finger 2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
THP2, HPE9, THP1
%HI
4.89(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.97(Read more about gnomAD pLI score)
LOEUF
0.31(Read more about gnomAD LOEUF score)
Cytoband
2q14.2
Genomic Coordinates
GRCh37/hg19: chr2:121493444-121750229 NCBI Ensembl UCSC
GRCh38/hg38: chr2:120735868-120992653 NCBI Ensembl UCSC
MANE Select Transcript
NM_001374353.1 ENST00000361492.9 (Read more about MANE Select)
Function
Functions as a transcription regulator in the hedgehog (Hh) pathway (PubMed:18455992, PubMed:26565916). Functions as a transcriptional activator (PubMed:9557682, PubMed:19878745, PubMed:24311597). May also function as transcriptional repressor (By similarity). Requires STK36 for full transcriptional activator activity. Required for normal embryonic development (PubMed:15994174, PubMed:20685856). {ECO:0000250|UniProtKB:Q0VGT2, ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:18455992, ECO:0000269|... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-2903
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
01/11/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 14581620
    Roessler et al (2003) reported 3 likely loss of function GLI2 variants in a cohort of 390 patients with holoprosencephaly (HPE). A W113X variant was described in a patient with bilateral cleft lip and palate, microcephaly, single central incisor, postaxial polydactyly and growth hormone deficiency. A deceased sibling had a single nostril, hypoplastic palate, alobar HPE and absent anterior lobe of the pituitary. However, DNA was not available for testing. The variant was not found in either parent. Additional variants identified include R168X in a proband referred for HPE findings and a splice site variant IVS5+1 G>A in a proband with hypotelorism, single nares, microcephaly, and growth hormone deficiency. The variants were found to be inherited from apparently normal fathers in both cases. Functional studies performed in Roessler et al (2005) suggest these three variants result in loss of function. Functional studies for additional truncating variants identified in the C-terminal activating domain suggested they may function as a dominant-negative. Reported variants were not found in >200 control chromosomes.
  • PUBMED: 21204792
    Bertolacini et al. (2012) report 2 patients with frameshift/nonsense variants. The first, p.Ser511fsX536, was described in a woman with midline facial dysmorphic features, postaxial polydactyly, and a normal MRI; the same change was also found in her mother with hypotelorism. The second, p.P288fsX301, was found in a patient with semilobar HPE, midline dysmorphic facial features, and postaxial polydactyly; the same change was also found in the patient's mother, who had postaxial polydactyly.
  • PUBMED: 24744436
    Bear et al (2014) screened ~400 individuals with HPE spectrum disorders, endocrine disorders or craniofacial anomalies for variants in GLI2. Two large deletions were identified involving most of the gene. The first was a 118 kb deletion including coding exons 3-13 in a mother and two daughters. The mother had midface hypoplasia and short stature and both daughters had polydactyly and growth hormone deficiency. A 151 kb deletion of coding exons 2-13 was detected in a patient with bilateral cleft lip and palate. Additionally, 7 nonsense variants, 8 frame shift variants and 1 splice site variant were identified in this cohort.
HI Evidence Comments:
There are known issues of variable expressivity and reduced penetrance associated with this phenotype. Additional reports of GLI2 deletions: PMID: 31862539 Melitza et al (2020) identified a de novo 229.9 kb deletion of chromosome 2q14.2 including coding exons 2-13 of GLI2 in a patient with combined pituitary hormone deficiency, pituitary anomalies and polydactyly. No additional genes were contained in the deletion. PMID: 33235745 A 90 kb deletion of exons 3-13 was reported by Elward et al (2020) in a mother and two daughters. The mother had polydactyly and both daughters had growth hormone deficiency and polydactyly.

Triplosensitivity (TS) Score Details

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

Genomic View

Select assembly: (NC_000002.11) (NC_000002.12)