GeneBe

GLI1

protein-coding

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

Gene summary

This gene encodes a member of the Kruppel family of zinc finger proteins. The encoded transcription factor is activated by the sonic hedgehog signal transduction cascade and regulates stem cell proliferation. The activity and nuclear localization of this protein is negatively regulated by p53 in an inhibitory loop. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

Previous symbols:
  • GLI

MANE transcript

NM_005269.3

Inheritance

AR, AD

ClinVar variants

P:17U:169B:42

Top phenotype

Polydactyly, postaxial, type A8; Polydactyly, preaxial I

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr12:57,459,785-57,472,268

External References & Databases

Ensembl (ENSG00000111087)NCBI Gene (2735)OMIM (165220)HGNC:4317GenCCUniProt (P08151)AlphaFoldClinVar (GLI1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~12.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

polydactyly of a biphalangeal thumbLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0008269

Submitter: Ambry Genetics

polydactyly, postaxial, type A8LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0029130

Submitter: Labcorp Genetics (formerly Invitae)

postaxial polydactyly type ASUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019673

Submitter: Orphanet

polydactyly of a biphalangeal thumbSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008269

Submitter: PanelApp Australia

polydactyly of a biphalangeal thumbSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008269

Submitter: Orphanet

polydactyly, postaxial, type A8STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0029130

Submitter: PanelApp Australia

Ellis-van Creveld syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009162

Submitter: Orphanet

postaxial polydactylySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0020927

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Polydactyly, postaxial, type A8; Polydactyly, preaxial IAR

Manifestation: Musculoskeletal

Intervention: General

Rationale: 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

Refs: 28973407; 30620395Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GLI1 variants in ClinVar

10 Conditions Cataloged
not specifiedTotal: 166
not providedTotal: 36
GLI1-related disorderTotal: 26
Polydactyly, postaxial, type A8Total: 11
Polydactyly of a biphalangeal thumbTotal: 3
Autosomal recessive GLI1-related disordersTotal: 2
Premature ovarian failureTotal: 1
Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005269.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
4
clinvar
29
clinvar
4
clinvar
 37
missense
1
clinvar
1
clinvar
161
clinvar
6
clinvar
3
clinvar
 172
nonsense
3
clinvar
4
clinvar
1
clinvar
 8
start loss
0
frameshift
1
clinvar
5
clinvar
2
clinvar
 8
splice donor/acceptor (+/-2bp)
2
clinvar
1
clinvar
 3
Total512169357228

Highest pathogenic variant AF is 0.00003717684

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_005269.3RefSeqNP_005260.111MANE Select
ENST00000228682.7EnsemblENSP00000228682.211MANE Select
NM_001160045.2RefSeqNP_001153517.19Standard
NM_001167609.2RefSeqNP_001161081.110Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
gli1Danio rerio

Structure: retinal ganglion cell

Quality: misrouted

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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

Biological Process

  • osteoblast differentiation
  • smoothened signaling pathway
  • spermatogenesis
  • ventral midline development
  • positive regulation of cell population proliferation

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

Cellular Component

  • nucleus
  • nucleoplasm
  • cytoplasm
  • cytosol
  • axoneme

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000228682
Coding exons
11
Length
12128
Individuals with no LoFs
125687
Homozygous LoFs
0
Heterozygous LoFs
61
Defined
125748
p
0.000243
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.085806580.8820.00003767095
Missense (PolyPhen)278318.440.872993457
Synonymous0.9872342540.9210.00001342411
Loss of Function1.942740.30.6700.00000220448

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.0000910.000087rare
Ashkenazi Jewish0.000600.00060rare
East Asian0.000170.00016rare
Finnish0.000140.00014rare
European (Non-Finnish)0.000320.00031rare
South Asian0.000260.00026rare
Other0.000160.00016rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.564

Intolerance Scores

LoFtool
0.786
RVIS EVS
-0.88
RVIS percentile EVS
10.56

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.836

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
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