GLI1

GLI family zinc finger 1, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 12:57459784-57472268

Previous symbols: [ "GLI" ]

Links

ENSG00000111087 ∙ NCBI:2735 ∙ OMIM:165220 ∙ HGNC:4317 ∙ Uniprot:P08151 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• polydactyly of a biphalangeal thumb (Limited), mode of inheritance: AR
• Ellis-van Creveld syndrome (Supportive), mode of inheritance: AR
• postaxial polydactyly type A (Supportive), mode of inheritance: AR
• polydactyly of a biphalangeal thumb (Supportive), mode of inheritance: AD
• polydactyly, postaxial, type A8 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Polydactyly, postaxial, type A8; Polydactyly, preaxial I	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	28973407; 30620395

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GLI1 gene.

• Inborn genetic diseases (35 variants)
• not provided (27 variants)
• Polydactyly, postaxial, type A8 (9 variants)
• Preaxial hand polydactyly (4 variants)
• not specified (3 variants)
• GLI1-related condition (2 variants)
• Premature ovarian failure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLI1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				8	5	13
missense			41	4	5	50
nonsense	2	1				3
start loss						0
frameshift		2	2			4
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			1			1
non coding			1			1
Total	2	4	44	12	10

Highest pathogenic variant AF is 0.00000658

Variants in GLI1

This is a list of pathogenic ClinVar variants found in the GLI1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-57464042-C-T		GLI1-related disorder	Likely benign (May 28, 2019)
12-57464074-C-T		not specified	Uncertain significance (Jan 04, 2022)
12-57464746-G-A		GLI1-related disorder	Likely benign (Mar 11, 2019)
12-57464770-G-A		GLI1-related disorder	Benign/Likely benign (Dec 31, 2019)
12-57464793-C-A		GLI1-related disorder	Likely benign (Dec 31, 2019)
12-57464816-C-T		Polydactyly, postaxial, type A8	Pathogenic (Jan 03, 2022)
12-57464842-C-T		GLI1-related disorder	Likely benign (Oct 01, 2022)
12-57465160-C-G		not specified	Uncertain significance (May 24, 2023)
12-57465179-C-T		not specified	Uncertain significance (May 03, 2023)
12-57465181-T-C		not specified	Uncertain significance (Jul 14, 2021)
12-57465191-A-G		not specified	Uncertain significance (Sep 20, 2023)
12-57465203-G-A		not specified	Likely benign (Jan 03, 2024)
12-57465224-C-G		GLI1-related disorder	Benign (Nov 01, 2023)
12-57465251-G-A		Malignant tumor of prostate	Uncertain significance (-)
12-57465255-G-A			Uncertain significance (Jun 16, 2022)
12-57465638-A-C		not specified	Uncertain significance (Mar 17, 2023)
12-57465648-G-A		Preaxial hand polydactyly • Polydactyly, postaxial, type A8 • GLI1-related disorder	Benign (Aug 10, 2021)
12-57465822-A-G		not specified	Uncertain significance (Sep 14, 2022)
12-57465836-G-A		not specified	Uncertain significance (Jul 14, 2021)
12-57465841-G-A			Likely benign (Dec 31, 2019)
12-57465843-G-A		not specified	Uncertain significance (Feb 23, 2023)
12-57465876-G-T		GLI1-related disorder	Uncertain significance (Jan 22, 2024)
12-57466263-C-T		GLI1-related disorder	Benign (Feb 21, 2019)
12-57466291-T-TG			Likely pathogenic (Dec 24, 2021)
12-57466293-G-T		Polydactyly, postaxial, type A8	Conflicting classifications of pathogenicity (Feb 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GLI1	protein_coding	protein_coding	ENST00000228682	11	12128

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.66e-14	0.843	125687	0	61	125748	0.000243

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.08	580	658	0.882	0.0000376	7095
Missense in Polyphen		278	318.44	0.87299		3457
Synonymous	0.987	234	254	0.921	0.0000134	2411
Loss of Function	1.94	27	40.3	0.670	0.00000220	448

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000215	0.000214
Ashkenazi Jewish	0.000595	0.000595
East Asian	0.000167	0.000163
Finnish	0.000142	0.000139
European (Non-Finnish)	0.000315	0.000308
Middle Eastern	0.000167	0.000163
South Asian	0.000262	0.000261
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a transcriptional activator (PubMed:19706761, PubMed:10806483, PubMed:19878745, PubMed:24311597, PubMed:24217340). Binds to the DNA consensus sequence 5'- GACCACCCA-3' (PubMed:2105456, PubMed:8378770, PubMed:24217340). May regulate the transcription of specific genes during normal development (PubMed:19706761). May play a role in craniofacial development and digital development, as well as development of the central nervous system and gastrointestinal tract. Mediates SHH signaling (PubMed:19706761). Plays a role in cell proliferation and differentiation via its role in SHH signaling (Probable). {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:19706761, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:2105456, ECO:0000269|PubMed:24217340, ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:8378770, ECO:0000305}.
• Pathway: Basal cell carcinoma - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hedgehog signaling pathway - Homo sapiens (human);HH-Core;Dopaminergic Neurogenesis;Hedgehog ,on, state;Hedgehog ,off, state;EDA Signalling in Hair Follicle Development;Tumor suppressor activity of SMARCB1;Hedgehog Signaling Pathway;Hedgehog Signaling Pathway;Signal Transduction;Hedgehog;Hedgehog;Degradation of GLI1 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 (Consensus)

Recessive Scores

• pRec: 0.564

Intolerance Scores

• loftool: 0.786
• rvis_EVS: -0.88
• rvis_percentile_EVS: 10.56

Haploinsufficiency Scores

• pHI: 0.983
• hipred: Y
• hipred_score: 0.637
• ghis: 0.568

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.836

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gli1
• Phenotype: neoplasm; reproductive system phenotype; normal 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); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; limbs/digits/tail 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); endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: gli1
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: misrouted

Gene ontology

• Biological process: osteoblast differentiation;smoothened signaling pathway;spermatogenesis;ventral midline development;positive regulation of cell population proliferation;regulation of smoothened signaling pathway;response to wounding;epidermal cell differentiation;dorsal/ventral pattern formation;proximal/distal pattern formation;cerebellar cortex morphogenesis;smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation;pituitary gland development;lung development;prostate gland development;regulation of osteoblast differentiation;positive regulation of DNA replication;positive regulation of smoothened signaling pathway;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;digestive tract morphogenesis;notochord regression;positive regulation of cardiac muscle cell proliferation;canonical Wnt signaling pathway;negative regulation of canonical Wnt signaling pathway;liver regeneration;positive regulation of cell cycle G1/S phase transition;regulation of hepatocyte proliferation
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;axoneme;ciliary tip;ciliary base
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;chromatin binding;protein binding;microtubule binding;transcription regulatory region DNA binding;metal ion binding