GLI1
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Summary
GLI1 (GLI family zinc finger 1, HGNC:4317) is a protein-coding gene on chromosome 12q13.3, encoding Zinc finger protein GLI1 (P08151). Acts as a transcriptional activator.
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.
Source: NCBI Gene 2735 — RefSeq curated summary.
At a glance
- Gene–disease (curated): postaxial polydactyly (Strong, GenCC) — +4 more curated relationships
- Clinical variants (ClinVar): 218 total — 5 pathogenic, 5 likely-pathogenic
- Phenotypes (HPO): 58
- Druggable target: yes — 1 molecules with ChEMBL bioactivity
- Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
- Transcription factor: yes — 184 downstream targets (CollecTRI)
- MANE Select transcript:
NM_005269
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:4317 |
| Approved symbol | GLI1 |
| Name | GLI family zinc finger 1 |
| Location | 12q13.3 |
| Locus type | gene with protein product |
| Status | Approved |
| Ensembl gene | ENSG00000111087 |
| Ensembl biotype | protein_coding |
| OMIM | 165220 |
| Entrez | 2735 |
Gene structure
Transcript identifiers
Ensembl transcripts: 9 — 7 protein_coding, 2 retained_intron
ENST00000228682, ENST00000527742, ENST00000528432, ENST00000528467, ENST00000530789, ENST00000532291, ENST00000543426, ENST00000546141, ENST00000907055
RefSeq mRNA: 3 — MANE Select: NM_005269
NM_001160045, NM_001167609, NM_005269
CCDS: CCDS53806, CCDS53807, CCDS8940
Canonical transcript exons
ENST00000228682 — 12 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000751003 | 57465111 | 57465255 |
| ENSE00000751004 | 57465607 | 57465696 |
| ENSE00000751005 | 57465788 | 57465925 |
| ENSE00000751008 | 57467994 | 57468224 |
| ENSE00000751009 | 57469431 | 57469698 |
| ENSE00001278393 | 57470317 | 57472268 |
| ENSE00001619249 | 57463999 | 57464091 |
| ENSE00001621207 | 57467333 | 57467497 |
| ENSE00001733880 | 57466240 | 57466389 |
| ENSE00002170467 | 57459785 | 57460201 |
| ENSE00002313701 | 57463665 | 57463791 |
| ENSE00003678546 | 57464673 | 57464868 |
Expression profiles
Bgee: expression breadth ubiquitous, 173 present calls, max score 92.43.
FANTOM5 (CAGE): breadth broad, TPM avg 1.4481 / max 54.2742, expressed in 541 samples.
FANTOM5 promoters (6 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 126216 | 0.4348 | 225 |
| 126218 | 0.3536 | 186 |
| 126220 | 0.2416 | 120 |
| 126217 | 0.2135 | 117 |
| 126215 | 0.1265 | 47 |
| 126219 | 0.0780 | 28 |
Top tissues by expression
280 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| tibial nerve | UBERON:0001323 | 92.43 | gold quality |
| olfactory bulb | UBERON:0002264 | 84.18 | gold quality |
| type B pancreatic cell | CL:0000169 | 83.81 | gold quality |
| triceps brachii | UBERON:0001509 | 83.39 | gold quality |
| heart right ventricle | UBERON:0002080 | 83.30 | gold quality |
| sural nerve | UBERON:0015488 | 83.18 | gold quality |
| skeletal muscle tissue of rectus abdominis | UBERON:0004511 | 82.80 | gold quality |
| mucosa of stomach | UBERON:0001199 | 82.11 | gold quality |
| gluteal muscle | UBERON:0002000 | 81.67 | gold quality |
| endocervix | UBERON:0000458 | 80.35 | gold quality |
| diaphragm | UBERON:0001103 | 79.53 | gold quality |
| vena cava | UBERON:0004087 | 79.44 | gold quality |
| tongue squamous epithelium | UBERON:0006919 | 79.26 | gold quality |
| nasal cavity epithelium | UBERON:0005384 | 79.19 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 79.17 | gold quality |
| dorsal motor nucleus of vagus nerve | UBERON:0002870 | 78.66 | silver quality |
| rectum | UBERON:0001052 | 78.48 | gold quality |
| blood | UBERON:0000178 | 78.36 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 78.30 | gold quality |
| myocardium | UBERON:0002349 | 78.13 | gold quality |
| skeletal muscle tissue of biceps brachii | UBERON:0004502 | 78.06 | gold quality |
| stromal cell of endometrium | CL:0002255 | 77.73 | gold quality |
| smooth muscle tissue | UBERON:0001135 | 77.66 | gold quality |
| gall bladder | UBERON:0002110 | 77.62 | gold quality |
| orbitofrontal cortex | UBERON:0004167 | 77.47 | gold quality |
| dorsal root ganglion | UBERON:0000044 | 77.30 | gold quality |
| Brodmann (1909) area 46 | UBERON:0006483 | 77.03 | gold quality |
| layer of synovial tissue | UBERON:0007616 | 76.73 | gold quality |
| right coronary artery | UBERON:0001625 | 76.64 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 76.58 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 0.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | no | 3.32 |
Regulation
Is transcription factor: yes
Downstream targets (CollecTRI)
184 targets.
| Target | Regulation |
|---|---|
| ABCB1 | |
| ABCG2 | Repression |
| ADAM12 | Repression |
| AKT1 | Unknown |
| ALCAM | Repression |
| AMH | Repression |
| ANGPT4 | Activation |
| AQP1 | Activation |
| ARTN | Activation |
| ATG12 | Repression |
| BCL2 | Activation |
| BHLHE41 | Activation |
| BIRC3 | Activation |
| BMI1 | Activation |
| CAMK1D | Activation |
| CCN1 | Activation |
| CCND1 | Unknown |
| CCND2 | Activation |
| CCPG1 | Repression |
| CD24 | Activation |
| CDC14A | Activation |
| CDH1 | Activation |
| CDH17 | |
| CDK2 | Activation |
| CDKN1A | Repression |
| CEL | |
| CFLAR | Unknown |
| CLCA1 | Repression |
| CLCA2 | Repression |
| CLDN2 | Activation |
Upstream regulators (CollecTRI, top): ACTRT1, BCL6, BCOR, DCAF7, EWSR1, EYA1, FLI1, GLI1, GLI2, GLI3, H1-4, H3-3A, H3-3B, H4C2, HES1, MEOX1, RUNX2, SIRT1, SMAD2, SMAD4, SMARCB1, SMO, TP53, TWIST1
miRNA regulators (miRDB)
16 targeting GLI1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-3134 | 100.00 | 66.43 | 777 |
| HSA-MIR-4533 | 100.00 | 69.48 | 2758 |
| HSA-MIR-4496 | 99.88 | 68.89 | 2236 |
| HSA-MIR-1299 | 99.77 | 71.24 | 2389 |
| HSA-MIR-4679 | 99.76 | 69.19 | 1229 |
| HSA-MIR-1255A | 99.74 | 68.09 | 744 |
| HSA-MIR-1255B-5P | 99.74 | 68.16 | 741 |
| HSA-MIR-6733-3P | 99.54 | 67.80 | 1281 |
| HSA-MIR-4762-3P | 99.43 | 69.72 | 2363 |
| HSA-MIR-4279 | 99.19 | 66.70 | 2437 |
| HSA-MIR-4292 | 99.16 | 65.57 | 1767 |
| HSA-MIR-6791-5P | 99.16 | 65.92 | 1844 |
| HSA-MIR-361-5P | 98.95 | 70.16 | 1340 |
| HSA-MIR-6771-3P | 98.20 | 66.53 | 971 |
| HSA-MIR-4308 | 97.56 | 67.13 | 1385 |
| HSA-MIR-3943 | 95.87 | 64.57 | 523 |
Literature-anchored findings (GeneRIF, showing 40)
- Cooperative E-box regulation by TWIST and USF (PMID:11948912)
- Sonic hedgehog activates expression during prostate ductal bud formation (PMID:12221011)
- Loss of protein kinase Calpha expression may enhance the tumorigenic potential of Gli1 in basal cell carcinoma. (PMID:12907651)
- GLI-1 has a role in mediating bcl-2 transcriptional regulation by the sonic hedgehog signaling pathway (PMID:14555646)
- CDK4, MDM2, SAS and GLI genes are amplified in leiomyosarcoma, alveolar and embryonal rhabdomyosarcoma (PMID:15024701)
- GLI oncogene is activated through fusion with the beta-actin gene (ACTB) in a group of distinctive pericytic neoplasms (PMID:15111311)
- GLI2 directly activates GLI1 and retrovirally expressed GLI2 induces expression of endogenous GLI1 in human primary keratinocytes (PMID:15175043)
- Data report expression of sonic hedgehog-GLI-1 pathway components in adult human prostate cancer, often with enhanced levels in tumors versus normal prostatic epithelia. (PMID:15314219)
- characterization of the breakpoints of the ACTB-GLI and GLI-ACTB fusions at the genomic level in pericytoma with t(7;12) (PMID:15555571)
- Quantification of Gli1 transcripts by RT-PCR is helpful in discriminating BCC and trichoepithelioma from other skin tumors. (PMID:15606671)
- Elevated expression of hedgehog target genes human patched gene 1 (PTCH1) or Gli1 occurs in 63 of the 99 primary gastric cancers. (patched gene 1) (PMID:15905200)
- downregulation of Gli1 expression may be an important mechanism by which KAAD-cyclopamine inhibits growth and induces apoptosis in esophageal cancer cells (PMID:16003737)
- GLI1 induction was apparently inhibited by PTCH1 (PMID:16229683)
- Protein kinase A regulates Gli1 localization and its transcriptional activity, in part, through modulating the nuclear localization signal function. (PMID:16293631)
- GLI target gene profiles correlated well with the biological activities of these transcription factors in hair follicles and basal cell carcinoma. (PMID:16434164)
- Increased expression of SHh mRNA in human colonic adenocarcinomas and in a colorectal cell line with downstream increased expression of Gli1 mRNA known to promote cell proliferation. (PMID:16701100)
- beta-catenin might be involved in the Hh signaling pathway via enhancement of the transcriptional activity of GLI (PMID:16786128)
- The results suggest that epidermal growth factor receptor (EGFR) signaling modulates GLI target gene profiles which may play an important regulatory role in outer root sheath (ORS) specification, hair growth, and possibly cancer. (PMID:16880536)
- AN11 may be a physiological regulator of GLI1 transcriptional activity (PMID:16887337)
- Expressions of Shh and Gli-1 were significantly higher in leiomyomas than in gastrointestinal stromal tumors. Expressions of Ptc and Smo did not correlate with histopathological differentiation. (PMID:17007023)
- SCCRO regulates Gli1–a key regulator of the hedgehog (HH) pathway. (PMID:17018598)
- gastrointestinal neuroendocrine carcinoma cell lines express Gli1 mRNA significantly. (PMID:17102592)
- Hedgehog transcription factor Gli1 is targeted by Numb for Itch-dependent ubiquitination, which suppresses Hedgehog signals, thus arresting growth and promoting cell differentiation. (PMID:17115028)
- In esophageal squamous cell carcinoma, Gli-1 expression was associated with tumor depth (p < 0.001), positive lymph node metastasis (p = 0.004) and a poor prognosis (p = 0.0047). (PMID:17179732)
- GLI signaling regulates the expression of stemness genes in and the self-renewal of CD133(+) glioma cancer stem cells. (PMID:17196391)
- Melanomas require SHH-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways. (PMID:17392427)
- Shh-Ptch1-Gli1 signaling pathway may play a role in the progression of colorectal tumor. (PMID:17461467)
- mRNA expression of the hedgehog pathway target Gli1 is relatively high in approximately 25% of glioblastoma multiforme cases. Reduction of Gli levels using siRNA also reduced the viability and growth of glioma cells. (PMID:17628016)
- transforming growth factor-beta has a role in Smad3-dependent activation of Gli2 and Gli1 expression (PMID:17638910)
- Down-regulation of Bcl-2 plays an important role in apoptosis induced by Gli-1 siRNA in hepatocellular carcinoma cells (PMID:18203291)
- GLI1 does not routinely co-operate with ERK to induce the formation of basal cell carcinoma skin cancers. (PMID:18281251)
- activation mechanism of the terminal transducer of the pathway, GLI1, is mediated not only by GLI1FL but also by the GLI1DeltaN variant (PMID:18378682)
- members of the Hh pathway, especially Gli1, play an important role in the invasiveness of pancreatic cancer cells through the regulation of MMP-9 expression. (PMID:18410405)
- SHH and Gli1 mRNAs are likely to be up-regulated from adenoma and from borderline to carcinoma cells, respectively, in intraductal papillary mucinous neoplasm of the pancreas (PMID:18425375)
- Gli-1 nuclear expression is a strong and independent predictor of early relapse and poor prognosis in Esophageal Squamous Carcinoma after ChemoRadioTherapy - which suggests that Hh signal activation might promote cancer regrowth and progression after CRT (PMID:18475300)
- These results indicate a significant role for Shh-GLI signaling in the proliferation of mantle cell lymphoma. (PMID:18524848)
- Hh target genes GLI1 and PTCH1 are not expressed in lesional psoriatic skin (PMID:18754037)
- A role ofor SIL in derepressing GLI1 from the negative control of SUFU. (PMID:18829525)
- p53 and GLI1 may have a role in tumor cell survival (PMID:18924150)
- Protein kinase Cdelta alters hedgehog signaling by inhibition of Gli protein transcriptional activity (PMID:19015273)
Cross-species orthologs
3 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | gli1 | ENSDARG00000101244 |
| mus_musculus | Gli1 | ENSMUSG00000025407 |
| rattus_norvegicus | Gli1 | ENSRNOG00000025120 |
Paralogs (14): ZIC2 (ENSG00000043355), ZXDC (ENSG00000070476), GLI2 (ENSG00000074047), GLI3 (ENSG00000106571), GLIS3 (ENSG00000107249), GLIS2 (ENSG00000126603), AEBP2 (ENSG00000139154), ZIC5 (ENSG00000139800), ZIC1 (ENSG00000152977), ZIC3 (ENSG00000156925), GLIS1 (ENSG00000174332), ZIC4 (ENSG00000174963), ZXDA (ENSG00000198205), ZXDB (ENSG00000198455)
Protein
Protein identifiers
Zinc finger protein GLI1 — P08151 (reviewed: P08151)
Alternative names: Glioma-associated oncogene, Oncogene GLI
All UniProt accessions (3): E9PIB9, E9PQQ1, P08151
UniProt curated annotations — full annotation on UniProt →
Function. Acts as a transcriptional activator. Binds to the DNA consensus sequence 5’-GACCACCCA-3’. Regulates the transcription of specific genes during normal development. Plays a role in craniofacial development and digital development, as well as development of the central nervous system and gastrointestinal tract. Mediates SHH signaling. Plays a role in cell proliferation and differentiation via its role in SHH signaling. Acts as a transcriptional activator, but activates a different set of genes than isoform 1. Activates expression of CD24, unlike isoform 1. Mediates SHH signaling. Promotes cancer cell migration.
Subunit / interactions. Interacts with KIF7. Interacts with STK36. Interacts with ZIC1; the interaction enhances transcription activation. Interacts with SUFU; this inhibits transcriptional activation by GLI1.
Subcellular location. Cytoplasm. Nucleus Cytoplasm. Nucleus.
Tissue specificity. Detected in testis (at protein level). Testis, myometrium and fallopian tube. Also expressed in the brain with highest expression in the cerebellum, optic nerve and olfactory tract. Isoform 1 is detected in brain, spleen, pancreas, liver, kidney and placenta; isoform 2 is not detectable in these tissues.
Post-translational modifications. Phosphorylated in vitro by ULK3. Acetylation at Lys-518 down-regulates transcriptional activity. Deacetylated by HDAC1. Ubiquitinated by the CRL2(FEM1B) complex, suppressing GLI1 transcriptional activator activity.
Disease relevance. Polydactyly, postaxial, A8 (PAPA8) [MIM:618123] A form of postaxial polydactyly, a condition characterized by the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type A, the extra digit is well-formed and articulates with the fifth or a sixth metacarpal/metatarsal. PAPA8 is an autosomal recessive condition characterized by the presence of postaxial extra digits (hexadactyly) on the hands and/or the feet. The disease is caused by variants affecting the gene represented in this entry. Polydactyly, preaxial 1 (PPD1) [MIM:174400] A form of polydactyly, a condition defined by the occurrence of supernumerary digits in the upper and/or lower extremities. Preaxial or radial polydactyly refers to the presence of extra digits on the radial side of the hand. PPD1 is an autosomal recessive form characterized by duplication of the distal phalanx of the thumb. The disease may be caused by variants affecting the gene represented in this entry.
Induction. Isoform 1 and isoform 2 are amplified in glioblastoma cells.
Miscellaneous. Undetectable in normal cells but highly expressed in cancer cells.
Similarity. Belongs to the GLI C2H2-type zinc-finger protein family.
Isoforms (3)
| UniProt ID | Names | Canonical? |
|---|---|---|
| P08151-1 | 1 | yes |
| P08151-2 | 2, tGLI1 | |
| P08151-3 | 3 |
RefSeq proteins (3): NP_001153517, NP_001161081, NP_005260* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR013087 | Znf_C2H2_type | Domain |
| IPR036236 | Znf_C2H2_sf | Homologous_superfamily |
| IPR043359 | GLI-like | Family |
| IPR056436 | Znf-C2H2_ZIC1-5/GLI1-3-like | Domain |
Pfam: PF00096, PF23561
UniProt features (52 total): region of interest 11, sequence variant 11, compositionally biased region 6, zinc finger region 5, strand 5, helix 5, turn 3, splice variant 2, chain 1, modified residue 1, cross-link 1, sequence conflict 1
Structure
Experimental structures (PDB)
5 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 4KMD | X-RAY DIFFRACTION | 1.7 |
| 7T91 | X-RAY DIFFRACTION | 2.05 |
| 2GLI | X-RAY DIFFRACTION | 2.6 |
| 4BLB | X-RAY DIFFRACTION | 2.8 |
| 5OM0 | X-RAY DIFFRACTION | 3.2 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P08151-F1 | 46.19 | 0.00 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Post-translational modifications (2): 518, 1003
Function
Pathways and Gene Ontology
Reactome pathways
4 pathways
| ID | Pathway |
|---|---|
| R-HSA-5610780 | Degradation of GLI1 by the proteasome |
| R-HSA-5610787 | Hedgehog ‘off’ state |
| R-HSA-5632684 | Hedgehog ‘on’ state |
| R-HSA-5635851 | GLI proteins bind promoters of Hh responsive genes to promote transcription |
MSigDB gene sets: 409 (showing top):
GSE45365_NK_CELL_VS_CD11B_DC_UP, RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_HEPATOCYTE_PROLIFERATION, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_GLAND_MORPHOGENESIS, KEGG_HEDGEHOG_SIGNALING_PATHWAY, RORA1_01, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, AREB6_03, GOBP_CELL_CYCLE_PHASE_TRANSITION
GO Biological Process (34): osteoblast differentiation (GO:0001649), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), smoothened signaling pathway (GO:0007224), spermatid development (GO:0007286), ventral midline development (GO:0007418), positive regulation of cell population proliferation (GO:0008284), regulation of smoothened signaling pathway (GO:0008589), response to wounding (GO:0009611), epidermal cell differentiation (GO:0009913), dorsal/ventral pattern formation (GO:0009953), proximal/distal pattern formation (GO:0009954), cerebellar cortex morphogenesis (GO:0021696), regulation of cerebellar granule cell precursor proliferation (GO:0021936), pituitary gland development (GO:0021983), lung development (GO:0030324), positive regulation of cell migration (GO:0030335), prostate gland development (GO:0030850), regulation of osteoblast differentiation (GO:0045667), positive regulation of DNA replication (GO:0045740), positive regulation of smoothened signaling pathway (GO:0045880), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), digestive tract morphogenesis (GO:0048546), notochord regression (GO:0060032), positive regulation of cardiac muscle cell proliferation (GO:0060045), negative regulation of canonical Wnt signaling pathway (GO:0090090), liver regeneration (GO:0097421), positive regulation of cell cycle G1/S phase transition (GO:1902808), regulation of hepatocyte proliferation (GO:2000345), spermatogenesis (GO:0007283), anatomical structure morphogenesis (GO:0009653), regulation of gene expression (GO:0010468), cell differentiation (GO:0030154)
GO Molecular Function (13): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), chromatin binding (GO:0003682), microtubule binding (GO:0008017), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), double-stranded DNA binding (GO:0003690), protein binding (GO:0005515), metal ion binding (GO:0046872)
GO Cellular Component (11): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), axoneme (GO:0005930), ciliary basal body (GO:0036064), ciliary tip (GO:0097542), ciliary base (GO:0097546), GLI-SUFU complex (GO:1990788), cilium (GO:0005929)
Reactome top-level categories
Rollup of top-3 pathways:
| Category | Pathways |
|---|---|
| Signaling by Hedgehog | 2 |
| Hedgehog ‘off’ state | 1 |
| Hedgehog ‘on’ state | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cellular anatomical structure | 6 |
| RNA polymerase II transcription regulatory region sequence-specific DNA binding | 3 |
| cilium | 3 |
| regionalization | 2 |
| gland development | 2 |
| binding | 2 |
| DNA binding | 2 |
| ossification | 1 |
| cell differentiation | 1 |
| DNA-templated transcription | 1 |
| regulation of gene expression | 1 |
| regulation of RNA biosynthetic process | 1 |
| regulation of DNA-templated transcription | 1 |
| transcription by RNA polymerase II | 1 |
| cell surface receptor signaling pathway | 1 |
| germ cell development | 1 |
| spermatid differentiation | 1 |
| central nervous system development | 1 |
| anatomical structure development | 1 |
| cell population proliferation | 1 |
| regulation of cell population proliferation | 1 |
| positive regulation of cellular process | 1 |
| smoothened signaling pathway | 1 |
| regulation of signal transduction | 1 |
| response to stress | 1 |
| epidermis development | 1 |
| epithelial cell differentiation | 1 |
| anatomical structure morphogenesis | 1 |
| cerebellum morphogenesis | 1 |
| cerebellar cortex development | 1 |
| cerebellar granule cell precursor proliferation | 1 |
| regulation of neural precursor cell proliferation | 1 |
| diencephalon development | 1 |
| endocrine system development | 1 |
| respiratory tube development | 1 |
| animal organ development | 1 |
| respiratory system development | 1 |
| cell migration | 1 |
| regulation of cell migration | 1 |
| positive regulation of cell motility | 1 |
Protein interactions and networks
STRING
3796 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| GLI1 | SUFU | Q9UMX1 | 999 |
| GLI1 | SHH | Q15465 | 976 |
| GLI1 | PTCH1 | Q13635 | 975 |
| GLI1 | SMO | Q99835 | 975 |
| GLI1 | KIF7 | Q2M1P5 | 966 |
| GLI1 | IHH | Q14623 | 961 |
| GLI1 | HHIP | Q96QV1 | 898 |
| GLI1 | STK36 | Q9NRP7 | 861 |
| GLI1 | SPOP | O43791 | 856 |
| GLI1 | CDC73 | Q6P1J9 | 841 |
| GLI1 | DHH | O43323 | 832 |
| GLI1 | BMI1 | P35226 | 816 |
| GLI1 | R4GMX3 | R4GMX3 | 816 |
| GLI1 | KAT2B | Q92831 | 815 |
| GLI1 | MYC | P01106 | 811 |
IntAct
91 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| GLI1 | SUFU | psi-mi:“MI:0407”(direct interaction) | 0.970 |
| SUFU | GLI1 | psi-mi:“MI:0407”(direct interaction) | 0.970 |
| GLI1 | SUFU | psi-mi:“MI:0915”(physical association) | 0.970 |
| SUFU | GLI1 | psi-mi:“MI:0915”(physical association) | 0.970 |
| GLI1 | SUFU | psi-mi:“MI:2364”(proximity) | 0.970 |
| Numb | GLI1 | psi-mi:“MI:0407”(direct interaction) | 0.610 |
| Numb | GLI1 | psi-mi:“MI:0915”(physical association) | 0.610 |
| GLI1 | Numb | psi-mi:“MI:0915”(physical association) | 0.610 |
| ITCH | GLI1 | psi-mi:“MI:0915”(physical association) | 0.600 |
| ITCH | GLI1 | psi-mi:“MI:0407”(direct interaction) | 0.600 |
| GLI1 | ITCH | psi-mi:“MI:0915”(physical association) | 0.600 |
BioGRID (214): PRKAA2 (Two-hybrid), GCC1 (Two-hybrid), TRIM42 (Two-hybrid), SMAD4 (Affinity Capture-Western), SMAD2 (Affinity Capture-Western), GLI1 (Affinity Capture-Western), BTRC (Affinity Capture-Western), GLI1 (Co-localization), GLI1 (Co-localization), SUFU (Affinity Capture-MS), TP53 (Affinity Capture-MS), ALLC (Affinity Capture-MS), ALYREF (Affinity Capture-MS), KIAA1211 (Affinity Capture-MS), SMARCA4 (Affinity Capture-MS)
ESM2 similar proteins: A1XSY8, O08656, O43474, P08046, P08151, P08152, P08154, P09022, P09027, P10070, P11161, P13360, P15976, P17679, P18146, P19544, P22561, P26632, P26633, P31249, P40656, P43300, P43301, P43429, P46153, P47806, P49639, P49952, P50476, P51774, Q05159, Q06889, Q07424, Q08427, Q0VGT2, Q29W20, Q60793, Q61169, Q6NW96, Q6P0J3
Diamond homologs: A0A5K4F1D0, A0JC51, A4FV57, O57311, O60481, O73689, O95409, P08151, P10070, P10071, P19538, P34708, P39768, P46684, P47806, P55878, P55879, Q0VGT2, Q15915, Q17308, Q5IS56, Q61467, Q61602, Q62520, Q62521, Q6DJQ6, Q6GR30, Q6XP49, Q6ZN18, Q7JNM3, Q7K0S9, Q7SXV2, Q7TQ40, Q8JJC0, Q8K1M4, Q8N9L1, Q8NBF1, Q8NEA6, Q8SV95, Q8VDL9
SIGNOR signaling
56 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| ZIC1 | up-regulates | GLI1 | relocalization |
| ZIC1 | up-regulates | GLI1 | |
| MTSS1 | up-regulates | GLI1 | binding |
| CXCL1 | up-regulates | GLI1 | |
| ITCH | down-regulates | GLI1 | ubiquitination |
| PTEN | down-regulates | GLI1 | |
| 2-[[3-[[2-(dimethylamino)phenyl]methyl]-2-pyridin-4-yl-1,3-diazinan-1-yl]methyl]-N,N-dimethylaniline | down-regulates | GLI1 | “chemical inhibition” |
| AKT2 | up-regulates | GLI1 | |
| NRAS | up-regulates | GLI1 | |
| NUMB | down-regulates | GLI1 | binding |
| 4-(2,4,5-tripyridin-4-yl-3-thiophenyl)pyridine | down-regulates | GLI1 | “chemical inhibition” |
| GLI1 | “up-regulates quantity by expression” | CCND1 | “transcriptional regulation” |
| GLI1 | “up-regulates quantity by expression” | MYCN | “transcriptional regulation” |
| GLI1 | “up-regulates quantity by expression” | PTCH1 | “transcriptional regulation” |
| RPS6KB1 | up-regulates | GLI1 | phosphorylation |
| GLI1 | up-regulates | Cell_growth | |
| SGK1 | down-regulates | GLI1 | binding |
| PRKAA1 | “down-regulates activity” | GLI1 | phosphorylation |
| DCAF7 | “down-regulates quantity by repression” | GLI1 | “transcriptional regulation” |
| ULK3 | “up-regulates activity” | GLI1 | phosphorylation |
| GLI1 | “form complex” | GLI1/GLI2 | binding |
| MAPK14 | “down-regulates quantity by destabilization” | GLI1 | phosphorylation |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 29 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| negative regulation of apoptotic process | 7 | 12.8× | 3e-04 |
Disease & clinical
Cancer significance
From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — LMS.
Clinical variants and AI predictions
ClinVar
218 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 5 |
| Likely pathogenic | 5 |
| Uncertain significance | 153 |
| Likely benign | 27 |
| Benign | 12 |
Top pathogenic / likely-pathogenic (10)
| Variant ID | HGVS | Classification |
|---|---|---|
| 3026491 | NM_005269.3(GLI1):c.1361del (p.Pro454fs) | Pathogenic |
| 3390852 | NM_005269.3(GLI1):c.1013G>T (p.Cys338Phe) | Pathogenic |
| 561213 | NM_005269.3(GLI1):c.2340G>A (p.Trp780Ter) | Pathogenic |
| 561214 | NM_005269.3(GLI1):c.1930C>T (p.Gln644Ter) | Pathogenic |
| 561215 | NM_005269.3(GLI1):c.337C>T (p.Arg113Ter) | Pathogenic |
| 2440510 | NM_005269.3(GLI1):c.821dup (p.Cys275fs) | Likely pathogenic |
| 2634349 | NM_005269.3(GLI1):c.1078-1G>C | Likely pathogenic |
| 3353391 | NM_005269.3(GLI1):c.2968C>T (p.Arg990Ter) | Likely pathogenic |
| 918147 | NM_005269.3(GLI1):c.1796del (p.Gly599fs) | Likely pathogenic |
| 982420 | NM_005269.3(GLI1):c.985A>T (p.Lys329Ter) | Likely pathogenic |
SpliceAI
1869 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 12:57460198:AGAGG:A | donor_loss | 1.0000 |
| 12:57460199:GAG:G | donor_gain | 1.0000 |
| 12:57460201:GGTG:G | donor_loss | 1.0000 |
| 12:57464832:G:GT | donor_gain | 1.0000 |
| 12:57465599:T:A | acceptor_gain | 1.0000 |
| 12:57465600:G:A | acceptor_gain | 1.0000 |
| 12:57465693:ACAGG:A | donor_loss | 1.0000 |
| 12:57465694:CAGGT:C | donor_loss | 1.0000 |
| 12:57465695:AG:A | donor_loss | 1.0000 |
| 12:57465696:GG:G | donor_loss | 1.0000 |
| 12:57465896:G:GT | donor_gain | 1.0000 |
| 12:57465897:A:T | donor_gain | 1.0000 |
| 12:57465926:G:GG | donor_gain | 1.0000 |
| 12:57465936:GGGG:G | donor_gain | 1.0000 |
| 12:57465937:G:GT | donor_gain | 1.0000 |
| 12:57466238:A:AG | acceptor_gain | 1.0000 |
| 12:57466239:G:GG | acceptor_gain | 1.0000 |
| 12:57467322:A:AG | acceptor_gain | 1.0000 |
| 12:57467322:AT:A | acceptor_gain | 1.0000 |
| 12:57467323:T:G | acceptor_gain | 1.0000 |
| 12:57467331:A:AG | acceptor_gain | 1.0000 |
| 12:57467332:G:GA | acceptor_gain | 1.0000 |
| 12:57468164:G:GT | donor_gain | 1.0000 |
| 12:57468175:G:GT | donor_gain | 1.0000 |
| 12:57468189:G:T | donor_gain | 1.0000 |
| 12:57468193:A:T | donor_gain | 1.0000 |
| 12:57470310:C:G | acceptor_gain | 1.0000 |
| 12:57470312:TGCA:T | acceptor_loss | 1.0000 |
| 12:57470313:GCAG:G | acceptor_loss | 1.0000 |
| 12:57470316:G:GC | acceptor_loss | 1.0000 |
AlphaMissense
7138 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 12:57465872:T:C | C237R | 1.000 |
| 12:57465899:T:C | F246L | 1.000 |
| 12:57465901:T:A | F246L | 1.000 |
| 12:57465901:T:G | F246L | 1.000 |
| 12:57465918:T:C | L252P | 1.000 |
| 12:57466279:T:C | F268L | 1.000 |
| 12:57466281:C:A | F268L | 1.000 |
| 12:57466281:C:G | F268L | 1.000 |
| 12:57466285:T:C | C270R | 1.000 |
| 12:57466286:G:A | C270Y | 1.000 |
| 12:57466287:C:G | C270W | 1.000 |
| 12:57466321:T:C | F282L | 1.000 |
| 12:57466322:T:C | F282S | 1.000 |
| 12:57466323:C:A | F282L | 1.000 |
| 12:57466323:C:G | F282L | 1.000 |
| 12:57466340:T:C | L288P | 1.000 |
| 12:57466348:C:G | H291D | 1.000 |
| 12:57466350:C:A | H291Q | 1.000 |
| 12:57466350:C:G | H291Q | 1.000 |
| 12:57466354:C:A | R293S | 1.000 |
| 12:57466362:C:A | H295Q | 1.000 |
| 12:57466362:C:G | H295Q | 1.000 |
| 12:57466384:T:A | C303S | 1.000 |
| 12:57466384:T:C | C303R | 1.000 |
| 12:57466385:G:C | C303S | 1.000 |
| 12:57466386:C:G | C303W | 1.000 |
| 12:57467342:T:C | C308R | 1.000 |
| 12:57467354:T:G | Y312D | 1.000 |
| 12:57467371:C:A | N317K | 1.000 |
| 12:57467371:C:G | N317K | 1.000 |
dbSNP variants (sampled 300 via entrez): RS1000032629 (12:57471809 T>C), RS1000076683 (12:57464244 C>A,T), RS1000458587 (12:57466735 T>C), RS1000611988 (12:57461859 G>A), RS1000688526 (12:57460604 G>A,T), RS1000953316 (12:57463259 C>T), RS1001240520 (12:57467023 A>G), RS1001368145 (12:57462928 A>G), RS1001503309 (12:57461123 C>T), RS1001955078 (12:57468400 A>C,G), RS1001963522 (12:57468750 A>G), RS1002118154 (12:57462225 C>T), RS1002180454 (12:57462172 G>A), RS1002240148 (12:57462408 C>T), RS1002279217 (12:57468691 G>A)
Disease associations
OMIM: gene MIM:165220 | disease phenotypes: MIM:618123, MIM:174400, MIM:209900
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| polydactyly of a biphalangeal thumb | Strong | Autosomal recessive |
| polydactyly, postaxial, type A8 | Strong | Autosomal recessive |
| postaxial polydactyly | Strong | Autosomal dominant |
| Ellis-van Creveld syndrome | Supportive | Autosomal recessive |
| postaxial polydactyly type A | Supportive | Autosomal recessive |
Mondo (8): polydactyly, postaxial, type A8 (MONDO:0029130), polydactyly of a biphalangeal thumb (MONDO:0008269), prostate cancer (MONDO:0008315), Bardet-Biedl syndrome (MONDO:0015229), primary ovarian failure (MONDO:0005387), Ellis-van Creveld syndrome (MONDO:0009162), postaxial polydactyly type A (MONDO:0019673), postaxial polydactyly (MONDO:0020927)
Orphanet (4): Polydactyly of a biphalangeal thumb and/or hallux (Orphanet:93339), Familial prostate cancer (Orphanet:1331), Bardet-Biedl syndrome (Orphanet:110), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)
HPO phenotypes
58 total (30 of 58 shown, HPO-id order):
| HPO | Term |
|---|---|
| HP:0000007 | Autosomal recessive inheritance |
| HP:0000008 | Abnormal morphology of female internal genitalia |
| HP:0000028 | Cryptorchidism |
| HP:0000039 | Epispadias |
| HP:0000047 | Hypospadias |
| HP:0000069 | Abnormality of the ureter |
| HP:0000072 | Hydroureter |
| HP:0000077 | Abnormality of the kidney |
| HP:0000164 | Abnormality of the dentition |
| HP:0000190 | Abnormal oral frenulum morphology |
| HP:0000233 | Thin vermilion border |
| HP:0000486 | Strabismus |
| HP:0000668 | Hypodontia |
| HP:0000684 | Delayed eruption of teeth |
| HP:0000691 | Microdontia |
| HP:0000774 | Narrow chest |
| HP:0000924 | Abnormality of the skeletal system |
| HP:0001161 | Hand polydactyly |
| HP:0001177 | Preaxial hand polydactyly |
| HP:0001231 | Abnormal fingernail morphology |
| HP:0001241 | Capitate-hamate fusion |
| HP:0001249 | Intellectual disability |
| HP:0001508 | Failure to thrive |
| HP:0001511 | Intrauterine growth retardation |
| HP:0001595 | Abnormal hair morphology |
| HP:0001597 | Abnormal nail morphology |
| HP:0001629 | Ventricular septal defect |
| HP:0001631 | Atrial septal defect |
| HP:0001651 | Dextrocardia |
| HP:0001654 | Abnormal heart valve morphology |
GWAS associations
0 associations (top):
MeSH disease descriptors (5)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D020788 | Bardet-Biedl Syndrome | C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125 |
| D004613 | Ellis-Van Creveld Syndrome | C05.116.099.708.327; C16.131.077.350.398; C16.131.831.350.398; C16.320.850.250.398; C17.800.804.350.398; C17.800.827.250.398 |
| D016649 | Primary Ovarian Insufficiency | C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750 |
| D011471 | Prostatic Neoplasms | C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750 |
| C536332 | Polydactyly preaxial type 1 (supp.) |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL5461 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 20,430 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL269277 | BETULINIC ACID | 1 | 20,430 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
PharmGKB variants
3 variants.
| Variant | Genes | Level | Score | #Clin annots | Drugs |
|---|---|---|---|---|---|
| rs2228226 | ARHGAP9, GLI1 | 0.00 | 0 | ||
| rs2228224 | GLI1 | 0.00 | 0 | ||
| rs2229300 | ARHGAP9, GLI1 | 0.00 | 0 |
Binding affinities (BindingDB)
2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value |
|---|---|---|
| NSC-287088 | IC50 | 620 nM |
| PHYSALIN F | IC50 | 660 nM |
ChEMBL bioactivities
24 potent at pChembl≥5 of 39 total, top 24 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 6.22 | IC50 | 600 | nM | PHYSALIN B |
| 6.21 | IC50 | 620 | nM | PHYSALIN B |
| 6.19 | IC50 | 640 | nM | CHEMBL4205868 |
| 6.18 | IC50 | 660 | nM | PHYSALIN F |
| 6.16 | IC50 | 700 | nM | CHEMBL504910 |
| 6.16 | IC50 | 700 | nM | CHEMBL5281322 |
| 6.13 | IC50 | 740 | nM | CHEMBL4214812 |
| 6.07 | IC50 | 860 | nM | CHEMBL4214812 |
| 5.96 | IC50 | 1090 | nM | CHEMBL4205868 |
| 5.80 | IC50 | 1600 | nM | CHEMBL1172835 |
| 5.75 | IC50 | 1800 | nM | STAUROSPORINONE |
| 5.75 | IC50 | 1800 | nM | CHEMBL193468 |
| 5.75 | IC50 | 1800 | nM | ARCYRIAFLAVIN C |
| 5.75 | IC50 | 1800 | nM | CHEMBL190546 |
| 5.58 | IC50 | 2600 | nM | CHEMBL1173148 |
| 5.38 | IC50 | 4200 | nM | CHEMBL5280113 |
| 5.33 | IC50 | 4700 | nM | CHEMBL516991 |
| 5.30 | IC50 | 5000 | nM | CYCLOPAMINE |
| 5.27 | IC50 | 5380 | nM | CHEMBL4206226 |
| 5.16 | IC50 | 6900 | nM | CHEMBL561023 |
| 5.15 | IC50 | 7100 | nM | ZERUMBONE |
| 5.05 | IC50 | 8980 | nM | CHEMBL4206743 |
| 5.03 | IC50 | 9400 | nM | CHEMBL551292 |
| 5.00 | IC50 | 1e+04 | nM | CHEMBL4453685 |
PubChem BioAssay actives
17 with measured affinity, of 178 total; 16 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| (1R,2S,5R,8S,9R,17R,18R,21S,24R,26S,27S)-5-hydroxy-2,9,26-trimethyl-3,19,23,28-tetraoxaoctacyclo[16.9.1.118,27.01,5.02,24.08,17.09,14.021,26]nonacosa-11,14-diene-4,10,22,29-tetrone | 1947019: Inhibition of GLI1 (unknown origin) transcriptional activity | ic50 | 0.6000 | uM |
| (1R,2R,4R,6S,11R,12S,15S,18S,19R,20S,21S,23R,26S)-15-hydroxy-11,18,21-trimethyl-5,17,24,28,29-pentaoxanonacyclo[17.9.1.11,20.02,12.04,6.06,11.015,19.018,23.021,26]triacont-8-ene-10,16,25,30-tetrone | 351770: Inhibition of Gli1-mediated transcription expressed in human PANC1 cells | ic50 | 0.6600 | uM |
| (1R,2S,5R,8S,9S,14R,15R,17R,18R,21S,24R,26S,27S)-14-chloro-5,15-dihydroxy-2,9,26-trimethyl-3,19,23,28-tetraoxaoctacyclo[16.9.1.118,27.01,5.02,24.08,17.09,14.021,26]nonacos-11-ene-4,10,22,29-tetrone | 1947019: Inhibition of GLI1 (unknown origin) transcriptional activity | ic50 | 0.7000 | uM |
| (1R,2R,4R,6S,11R,12S,15R,18S,19R,20S,21S,23R,26S)-15-hydroxy-11,18,21-trimethyl-5,17,24,28,29-pentaoxanonacyclo[17.9.1.11,20.02,12.04,6.06,11.015,19.018,23.021,26]triacont-8-ene-10,16,25,30-tetrone | 1947019: Inhibition of GLI1 (unknown origin) transcriptional activity | ic50 | 0.7000 | uM |
| 2-(3-benzoylphenyl)-N-(1H-indol-5-yl)-N-propylpropanamide | 491223: Inhibition of human Gli1 expressed in mouse C3H10T1/2 cells assessed as inhibition of transcriptional activity after 24 hrs by luciferase reporter gene assay | ic50 | 1.6000 | uM |
| 6-hydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17,19,21-nonaen-12-one | 351770: Inhibition of Gli1-mediated transcription expressed in human PANC1 cells | ic50 | 1.8000 | uM |
| 6,7-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17,19,21-nonaene-12,14-dione | 351770: Inhibition of Gli1-mediated transcription expressed in human PANC1 cells | ic50 | 1.8000 | uM |
| 3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4,6,8,10,15,17,19,21-nonaen-12-one | 351770: Inhibition of Gli1-mediated transcription expressed in human PANC1 cells | ic50 | 1.8000 | uM |
| 6,20-dihydroxy-3,13,23-triazahexacyclo[14.7.0.02,10.04,9.011,15.017,22]tricosa-1,4(9),5,7,10,15,17(22),18,20-nonaene-12,14-dione | 351770: Inhibition of Gli1-mediated transcription expressed in human PANC1 cells | ic50 | 1.8000 | uM |
| 2-(3-benzoylphenyl)-N-(1H-indol-6-yl)-N-propylpropanamide | 491223: Inhibition of human Gli1 expressed in mouse C3H10T1/2 cells assessed as inhibition of transcriptional activity after 24 hrs by luciferase reporter gene assay | ic50 | 2.6000 | uM |
| (1R,2S,5R,8S,9R,17R,18R,21S,24R,26S,27S)-5-hydroxy-2,9,26-trimethyl-3,19,23,28-tetraoxaoctacyclo[16.9.1.118,27.01,5.02,24.08,17.09,14.021,26]nonacosa-12,14-diene-4,10,22,29-tetrone | 1947019: Inhibition of GLI1 (unknown origin) transcriptional activity | ic50 | 4.2000 | uM |
| (1S,13S,15R,18R)-15-methoxy-5,7-dioxa-12-azapentacyclo[10.5.2.01,13.02,10.04,8]nonadeca-2,4(8),9,16-tetraen-18-ol | 1947018: Inhibition of GLI1-mediated transcriptional activity in human HaCaT cells coexpressing luciferase | ic50 | 4.7000 | uM |
| (2S)-2-(3-benzoylphenyl)-N-[2-(4-hydroxyphenyl)ethyl]-N-propylpropanamide | 421257: Inhibition of exogenously transfected human Gli1-mediated transcriptional activity in mouse C3H10T1/2 cells after 24 hrs by luciferase reporter gene assay | ic50 | 6.9000 | uM |
| (2E,6E,10E)-2,6,9,9-tetramethylcycloundeca-2,6,10-trien-1-one | 351770: Inhibition of Gli1-mediated transcription expressed in human PANC1 cells | ic50 | 7.1000 | uM |
| (2S)-2-(3-benzoylphenyl)-N,N-bis[2-(4-hydroxyphenyl)ethyl]propanamide | 421257: Inhibition of exogenously transfected human Gli1-mediated transcriptional activity in mouse C3H10T1/2 cells after 24 hrs by luciferase reporter gene assay | ic50 | 9.4000 | uM |
| N,N-dimethyldiazinane-3-carboxamide | 1632437: Inhibition of Shh-N-induced Gli1 (unknown origin) expressed in mouse Shh Light2 cells assessed as Gli1-mediated mediated transcription incubated for 30 hrs by firefly luciferase assay | ic50 | 10.0000 | uM |
CTD chemical–gene interactions
76 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Arsenic Trioxide | decreases expression, increases response to substance, decreases reaction, increases expression | 6 |
| GANT 61 | decreases expression, decreases reaction, increases expression | 4 |
| (+)-JQ1 compound | decreases reaction, increases expression, decreases expression | 4 |
| Resveratrol | affects cotreatment, decreases expression, decreases reaction, increases expression, decreases activity | 4 |
| cyclopamine | affects expression, decreases reaction, increases expression | 3 |
| sodium arsenite | affects cotreatment, decreases expression, increases expression | 3 |
| HhAntag691 | decreases reaction, affects cotreatment, affects reaction, decreases expression, increases expression (+1 more) | 3 |
| Aflatoxin B1 | decreases expression, increases expression, increases methylation | 3 |
| bisphenol A | decreases expression, increases expression | 2 |
| salinomycin | decreases expression | 2 |
| bisphenol S | decreases expression | 2 |
| Estradiol | affects cotreatment, increases expression, decreases reaction | 2 |
| Silicon Dioxide | decreases expression, increases expression | 2 |
| Cadmium Chloride | increases abundance, increases expression, affects reaction, affects cotreatment, decreases expression | 2 |
| Particulate Matter | increases abundance, decreases expression | 2 |
| bisphenol F | increases expression | 1 |
| pralsetinib | decreases reaction, increases expression, affects cotreatment, increases localization, increases phosphorylation | 1 |
| triphenyl phosphate | affects expression | 1 |
| lead acetate | affects cotreatment, decreases expression | 1 |
| embelin | decreases expression | 1 |
| ethyl-p-hydroxybenzoate | decreases expression | 1 |
| chromous chloride | affects cotreatment, decreases expression | 1 |
| cobaltous chloride | affects cotreatment, increases expression | 1 |
| ipriflavone | increases expression, decreases reaction | 1 |
| perfluorooctanoic acid | decreases expression | 1 |
| chromic oxide | decreases expression, affects cotreatment | 1 |
| nickel monoxide | increases expression, decreases reaction | 1 |
| ferrous chloride | decreases expression | 1 |
| evodiamine | increases expression | 1 |
| icariin | increases reaction, affects binding | 1 |
ChEMBL screening assays
44 unique, capped per target: 44 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1026025 | Binding | Inhibition of exogenously transfected human Gli1-mediated transcriptional activity in mouse C3H10T1/2 cells after 24 hrs by luciferase reporter gene assay | Structure-activity relationships and cancer-cell selective toxicity of novel inhibitors of glioma-associated oncogene homologue 1 (Gli1) mediated transcription. — J Med Chem |
Cellosaurus cell lines
8 cell lines: 4 cancer cell line, 3 embryonic stem cell, 1 transformed cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_A2G6 | SEES3-1V human GLI1, clone1 | Embryonic stem cell | Male |
| CVCL_A2G7 | SEES3-1V human GLI1, clone2 | Embryonic stem cell | Male |
| CVCL_A2G8 | SEES3-1V human GLI1, clone3 | Embryonic stem cell | Male |
| CVCL_B7U6 | e-hMEC-1 | Transformed cell line | |
| CVCL_B8WA | Abcam MCF-7 GLI1 KO | Cancer cell line | Female |
| CVCL_B9J2 | Abcam A-549 GLI1 KO | Cancer cell line | Male |
| CVCL_D7QN | Ubigene A-549 GLI1 KO | Cancer cell line | Male |
| CVCL_D8LX | Ubigene HCT 116 GLI1 KO | Cancer cell line | Male |
Clinical trials (associated diseases)
300 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT00029224 | PHASE4 | COMPLETED | Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions |
| NCT00035997 | PHASE4 | COMPLETED | Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis |
| NCT00063609 | PHASE4 | COMPLETED | The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy |
| NCT00103623 | PHASE4 | SUSPENDED | The Plenaxis® Experience Study |
| NCT00106392 | PHASE4 | COMPLETED | A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy |
| NCT00185029 | PHASE4 | UNKNOWN | MR-Lymphography and Lymph Node Staging in Prostate Cancer |
| NCT00199485 | PHASE4 | COMPLETED | Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer |
| NCT00219219 | PHASE4 | COMPLETED | Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases |
| NCT00219271 | PHASE4 | COMPLETED | Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer |
| NCT00237146 | PHASE4 | COMPLETED | Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy |
| NCT00242554 | PHASE4 | COMPLETED | Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases |
| NCT00280098 | PHASE4 | COMPLETED | Docetaxel in the Treatment of Hormone Refractory Prostate Cancer |
| NCT00293696 | PHASE4 | COMPLETED | Casodex/Zoladex Biomarkers in Localised Prostate Cancer |
| NCT00334139 | PHASE4 | COMPLETED | Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer |
| NCT00375765 | PHASE4 | COMPLETED | Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer |
| NCT00391690 | PHASE4 | COMPLETED | Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer |
| NCT00422708 | PHASE4 | COMPLETED | Local Anesthesia for Prostate Biopsy |
| NCT00526331 | PHASE4 | COMPLETED | Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy |
| NCT00590213 | PHASE4 | COMPLETED | Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX |
| NCT00629330 | PHASE4 | TERMINATED | Dissemination of Prostate Cancer Screening to PCP’s in African American Communities |
| NCT00771966 | PHASE4 | COMPLETED | Radical Prostatectomy and Perioperative Fluid Therapy |
| NCT00805701 | PHASE4 | COMPLETED | Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation |
| NCT00859027 | PHASE4 | COMPLETED | Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer |
| NCT00906269 | PHASE4 | UNKNOWN | Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer |
| NCT00953277 | PHASE4 | COMPLETED | Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer |
| NCT00982800 | PHASE4 | COMPLETED | Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy? |
| NCT01083199 | PHASE4 | COMPLETED | Global Performance Evaluation of the AMS CONTINUUM™ Device |
| NCT01136226 | PHASE4 | COMPLETED | Evaluate Recovery of Testosterone for Patients Using Eligard |
| NCT01161563 | PHASE4 | COMPLETED | Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration |
| NCT01230905 | PHASE4 | COMPLETED | Study to Monitor the Effects of Androgen Suppression Treatment on the Heart |
| NCT01296672 | PHASE4 | COMPLETED | 3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer |
| NCT01365143 | PHASE4 | TERMINATED | Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy |
| NCT01379742 | PHASE4 | UNKNOWN | Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy |
| NCT01486563 | PHASE4 | COMPLETED | Hydroxyethyl Starch and Renal Function After Radical Prostatectomy |
| NCT01511874 | PHASE4 | COMPLETED | Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer |
| NCT01512472 | PHASE4 | TERMINATED | Firmagon (Degarelix) Intermittent Therapy |
| NCT01547416 | PHASE4 | COMPLETED | The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function |
| NCT01571544 | PHASE4 | COMPLETED | The Use of Thermal Suits as Preventing Hypothermia During Surgery |
| NCT01581749 | PHASE4 | UNKNOWN | Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer |
| NCT01649635 | PHASE4 | COMPLETED | Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer |
Related Atlas pages
- Associated diseases: polydactyly of a biphalangeal thumb, polydactyly, postaxial, type A8, Ellis-van Creveld syndrome, postaxial polydactyly type A, postaxial polydactyly
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): Bardet-Biedl syndrome, Ellis-van Creveld syndrome, polydactyly of a biphalangeal thumb, polydactyly, postaxial, type A8, postaxial polydactyly, postaxial polydactyly type A