GLI2
GLI family zinc finger 2, the group of Zinc fingers C2H2-type
Basic information
Region (hg38): 2:120735623-120992653
Links
Phenotypes
GenCC
Source:
- holoprosencephaly 9 (Moderate), mode of inheritance: AD
- postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome (Moderate), mode of inheritance: AD
- postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome (Limited), mode of inheritance: AD
- holoprosencephaly 9 (Definitive), mode of inheritance: AD
- holoprosencephaly (Supportive), mode of inheritance: AR
- combined pituitary hormone deficiencies, genetic form (Supportive), mode of inheritance: AD
- postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome (Supportive), mode of inheritance: AD
- postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome (Definitive), mode of inheritance: AD
- postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome (Strong), mode of inheritance: AD
- holoprosencephaly 9 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Culler-Jones syndrome | AD | Endocrine | While initially reported (and named) as associated with holoprosencephaly the more classic presentation involves (sometimes subclinical) endocrinological manifestations, including treatable deficiency, such as of thyroid hormone and growth hormone, and awareness may allow endocrine-based testing and management to help amelioriate these manifestations | Craniofacial; Endocrine; Musculoskeletal; Neurologic | 14581620; 15994174; 17096318; 20685856; 22967285; 23112757; 23304807; 23408573; 24744436; 30629636 |
ClinVar
This is a list of variants' phenotypes submitted to
- Holoprosencephaly_9 (598 variants)
- Postaxial_polydactyly-anterior_pituitary_anomalies-facial_dysmorphism_syndrome (577 variants)
- not_provided (341 variants)
- Inborn_genetic_diseases (225 variants)
- GLI2-related_disorder (164 variants)
- not_specified (130 variants)
- Microform_holoprosencephaly (6 variants)
- Microcephaly (3 variants)
- See_cases (3 variants)
- Intellectual_disability (3 variants)
- Pituitary_stalk_interruption_syndrome (2 variants)
- Secondary_microcephaly (2 variants)
- Cerebellar_cyst (1 variants)
- Anophthalmia-microphthalmia_syndrome (1 variants)
- Abnormal_pinna_morphology (1 variants)
- Growth_delay (1 variants)
- Combined_pituitary_hormone_deficiencies,_genetic_form (1 variants)
- Skin_tags (1 variants)
- Congenital_cleft_nose (1 variants)
- Seizure (1 variants)
- Hypertelorism (1 variants)
- Arteriovenous_malformation (1 variants)
- Facial_asymmetry (1 variants)
- Intellectual_disability-microcephaly-strabismus-behavioral_abnormalities_syndrome (1 variants)
- CNS_hypomyelination (1 variants)
- Holoprosencephaly_1 (1 variants)
- Hypoplasia_of_the_corpus_callosum (1 variants)
- Poor_speech (1 variants)
- Abnormal_facial_shape (1 variants)
- Downturned_corners_of_mouth (1 variants)
- Hyperactivity (1 variants)
- Disorder_of_sexual_differentiation (1 variants)
- Exostoses (1 variants)
- Abnormal_optic_nerve_morphology (1 variants)
- Tessier_cleft (1 variants)
- Weaver_syndrome (1 variants)
- Sparse_and_thin_eyebrow (1 variants)
- Deeply_set_eye (1 variants)
- Abnormal_frontal_bone_morphology (1 variants)
- Male_infertility_with_azoospermia_or_oligozoospermia_due_to_single_gene_mutation (1 variants)
- Hand_tremor (1 variants)
- Upper_eyelid_coloboma (1 variants)
- Tremor (1 variants)
- Craniosynostosis_syndrome (1 variants)
- Limbal_dermoid (1 variants)
- Sparse_scalp_hair (1 variants)
- Partial_androgen_insensitivity_syndrome (1 variants)
- Hypotonia,_infantile,_with_psychomotor_retardation_and_characteristic_facies_1 (1 variants)
- Low-set_ears (1 variants)
- Pericallosal_lipoma (1 variants)
- Bardet-Biedl_syndrome (1 variants)
- Cerebral_arteriovenous_malformation (1 variants)
- Developmental_disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLI2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001374353.1. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 11 | 219 | 14 | 244 | ||
| missense | 570 | 96 | 678 | |||
| nonsense | 14 | 10 | 25 | |||
| start loss | 0 | |||||
| frameshift | 27 | 22 | 54 | |||
| splice donor/acceptor (+/-2bp) | 10 | |||||
| Total | 45 | 41 | 590 | 315 | 20 |
Highest pathogenic variant AF is 0.0000278815
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GLI2 | protein_coding | protein_coding | ENST00000452319 | 13 | 257031 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.973 | 0.0270 | 125718 | 0 | 30 | 125748 | 0.000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.817 | 896 | 967 | 0.926 | 0.0000661 | 10197 |
| Missense in Polyphen | 326 | 404.35 | 0.80622 | 4356 | ||
| Synonymous | 0.743 | 428 | 448 | 0.955 | 0.0000356 | 3362 |
| Loss of Function | 5.44 | 9 | 50.8 | 0.177 | 0.00000271 | 531 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000298 | 0.000297 |
| Ashkenazi Jewish | 0.0000995 | 0.0000992 |
| East Asian | 0.000326 | 0.000326 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000885 | 0.0000879 |
| Middle Eastern | 0.000326 | 0.000326 |
| South Asian | 0.000131 | 0.000131 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Functions as transcription regulator in the hedgehog (Hh) pathway (PubMed:18455992, PubMed:26565916). Functions as 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|PubMed:19878745, ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:26565916, ECO:0000269|PubMed:9557682, ECO:0000305|PubMed:20685856}.; FUNCTION: Isoform 5: Acts as a transcriptional repressor. {ECO:0000269|PubMed:15994174}.;
- Disease
- DISEASE: Holoprosencephaly 9 (HPE9) [MIM:610829]: A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. Holoprosencephaly type 9 is characterized by defective anterior pituitary formation and pan-hypopituitarism, with or without overt forebrain cleavage abnormalities, and holoprosencephaly-like midfacial hypoplasia. {ECO:0000269|PubMed:14581620, ECO:0000269|PubMed:17096318, ECO:0000269|PubMed:20685856}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Culler-Jones syndrome (CJS) [MIM:615849]: An autosomal dominant disorder characterized by a wide range of clinical manifestations. Clinical features include hypothalamic hamartoma, pituitary dysfunction, central or postaxial polydactyly, and syndactyly. Malformations are frequent in the viscera, e.g. anal atresia, bifid uvula, congenital heart malformations, pulmonary or renal dysplasia. {ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:20685856, ECO:0000269|PubMed:23408573}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Basal cell carcinoma - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hedgehog signaling pathway - Homo sapiens (human);Dopaminergic Neurogenesis;Hedgehog ,off, state;Tumor suppressor activity of SMARCB1;Hedgehog Signaling Pathway;Hedgehog Signaling Pathway;RUNX2 regulates chondrocyte maturation;RUNX2 regulates bone development;Transcriptional regulation by RUNX2;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;Hedgehog;RNA Polymerase II Transcription;Hedgehog;Degradation of GLI2 by the proteasome;Hedgehog ,off, state;GLI proteins bind promoters of Hh responsive genes to promote transcription;Hedgehog ,on, state;Signaling by Hedgehog;Hedgehog signaling events mediated by Gli proteins;Signaling events mediated by the Hedgehog family
(Consensus)
Recessive Scores
- pRec
- 0.341
Intolerance Scores
- loftool
- 0.345
- rvis_EVS
- -1.24
- rvis_percentile_EVS
- 5.38
Haploinsufficiency Scores
- pHI
- 0.978
- hipred
- Y
- hipred_score
- 0.875
- ghis
- 0.526
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.829
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gli2
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; vision/eye phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; embryo phenotype;
Zebrafish Information Network
- Gene name
- gli2a
- Affected structure
- retinal ganglion cell
- Phenotype tag
- abnormal
- Phenotype quality
- misrouted
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;skeletal system development;in utero embryonic development;kidney development;chondrocyte differentiation;osteoblast development;smoothened signaling pathway;pattern specification process;axon guidance;ventral midline development;hindgut morphogenesis;heart development;cell population proliferation;regulation of smoothened signaling pathway;anterior/posterior pattern specification;proximal/distal pattern formation;floor plate formation;spinal cord dorsal/ventral patterning;ventral spinal cord development;cerebellar cortex morphogenesis;smoothened signaling pathway involved in ventral spinal cord interneuron specification;smoothened signaling pathway involved in spinal cord motor neuron cell fate specification;smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation;spinal cord ventral commissure morphogenesis;pituitary gland development;lung development;mammary gland development;hindbrain development;negative regulation of chondrocyte differentiation;positive regulation of T cell differentiation in thymus;tube development;odontogenesis of dentin-containing tooth;embryonic digit morphogenesis;negative regulation of apoptotic process;positive regulation of neuron differentiation;positive regulation of DNA replication;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;embryonic digestive tract development;developmental growth;neuron development;branching morphogenesis of an epithelial tube;notochord regression;prostatic bud formation;mammary gland duct morphogenesis;smoothened signaling pathway involved in dorsal/ventral neural tube patterning;cellular response to organic cyclic compound;cochlea morphogenesis
- Cellular component
- nucleus;nucleoplasm;nucleolus;cytosol;cilium;axoneme;membrane;nuclear speck;motile cilium;ciliary tip;ciliary base
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;transcription factor binding;zinc ion binding;sequence-specific DNA binding;promoter-specific chromatin binding