GLI4

Summary

GLI4 (GLI family zinc finger 4, HGNC:4320) is a protein-coding gene on chromosome 8q24.3, encoding Zinc finger protein GLI4 (P10075).

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of DNA-templated transcription. Predicted to be located in nucleus.

Source: NCBI Gene 2738 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 107 total
• MANE Select transcript: NM_138465

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4320
Approved symbol	GLI4
Name	GLI family zinc finger 4
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	HKR4, ZNF928
Ensembl gene	ENSG00000250571
Ensembl biotype	protein_coding
OMIM	165280
Entrez	2738

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 16 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000340042, ENST00000344692, ENST00000517468, ENST00000517530, ENST00000519876, ENST00000520021, ENST00000521682, ENST00000522033, ENST00000522479, ENST00000523522, ENST00000523812, ENST00000891537, ENST00000891538, ENST00000891539, ENST00000891540, ENST00000891541, ENST00000914543, ENST00000914544, ENST00000962016, ENST00000962017

RefSeq mRNA: 1 — MANE Select: NM_138465 NM_138465

CCDS: CCDS6398

Canonical transcript exons

ENST00000340042 — 4 exons

Exon	Start	End
ENSE00003630743	143269360	143269520
ENSE00003676407	143274704	143274802
ENSE00003849683	143267445	143267484
ENSE00003891597	143275897	143276931

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 92.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.6616 / max 44.6244, expressed in 1759 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91395	7.6011	1759
91396	0.0605	28

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	92.35	gold quality
apex of heart	UBERON:0002098	91.55	gold quality
metanephros cortex	UBERON:0010533	91.45	gold quality
granulocyte	CL:0000094	91.27	gold quality
fundus of stomach	UBERON:0001160	91.06	gold quality
cortex of kidney	UBERON:0001225	90.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.62	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.42	gold quality
right uterine tube	UBERON:0001302	90.31	gold quality
transverse colon	UBERON:0001157	90.14	gold quality
Ammon’s horn	UBERON:0001954	90.13	gold quality
ectocervix	UBERON:0012249	89.81	gold quality
body of stomach	UBERON:0001161	89.63	gold quality
putamen	UBERON:0001874	89.61	gold quality
spleen	UBERON:0002106	89.57	gold quality
mucosa of transverse colon	UBERON:0004991	89.56	gold quality
small intestine	UBERON:0002108	89.55	gold quality
right frontal lobe	UBERON:0002810	89.51	gold quality
right ovary	UBERON:0002118	89.50	gold quality
cerebellar hemisphere	UBERON:0002245	89.49	gold quality
nucleus accumbens	UBERON:0001882	89.47	gold quality
endocervix	UBERON:0000458	89.41	gold quality
cerebellar cortex	UBERON:0002129	89.39	gold quality
cerebellum	UBERON:0002037	89.36	gold quality
esophagus mucosa	UBERON:0002469	89.31	gold quality
left ovary	UBERON:0002119	89.27	gold quality
skin of leg	UBERON:0001511	89.24	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.21	gold quality
temporal lobe	UBERON:0001871	89.19	gold quality
amygdala	UBERON:0001876	89.18	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting GLI4, 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-186-5P	99.99	70.83	3707
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4442	92.35	67.08	98

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
rattus_norvegicus	Gli4	ENSRNOG00000021765

Paralogs (176): ZNF195 (ENSG00000005801), ZNF112 (ENSG00000062370), ZNF275 (ENSG00000063587), ZNF37A (ENSG00000075407), ZNF510 (ENSG00000081386), ZNF506 (ENSG00000081665), ZNF268 (ENSG00000090612), MZF1 (ENSG00000099326), ZNF629 (ENSG00000102870), ZNF175 (ENSG00000105497), ZNF85 (ENSG00000105750), ZFP30 (ENSG00000120784), ZNF45 (ENSG00000124459), ZNF391 (ENSG00000124613), ZNF436 (ENSG00000125945), ZNF484 (ENSG00000127081), ZNF835 (ENSG00000127903), ZNF780B (ENSG00000128000), ZSCAN10 (ENSG00000130182), ZNF317 (ENSG00000130803), ZNF331 (ENSG00000130844), ZNF227 (ENSG00000131115), ZNF141 (ENSG00000131127), ZNF132 (ENSG00000131849), ZNF189 (ENSG00000136870), ZIM3 (ENSG00000141946), ZFP14 (ENSG00000142065), ZNF514 (ENSG00000144026), ZNF300 (ENSG00000145908), RBAK (ENSG00000146587), ZNF157 (ENSG00000147117), ZNF182 (ENSG00000147118), ZNF41 (ENSG00000147124), ZNF7 (ENSG00000147789), ZNF117 (ENSG00000152926), ZNF221 (ENSG00000159905), ZNF235 (ENSG00000159917), ZNF714 (ENSG00000160352), ZNF577 (ENSG00000161551), ZNF12 (ENSG00000164631)

Protein

Protein identifiers

Zinc finger protein GLI4 — P10075 (reviewed: P10075)

Alternative names: Krueppel-related zinc finger protein 4, Protein HKR4

All UniProt accessions (6): E5RFY1, E5RG07, E5RGM1, E5RIX4, P10075, H0YBH2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

RefSeq proteins (1): NP_612474* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (15 total): zinc finger region 7, compositionally biased region 2, region of interest 2, chain 1, modified residue 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10075-F1	65.92	0.22

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 (1): 86

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 29 (showing top): MAYBURD_RESPONSE_TO_L663536_UP, WEI_MYCN_TARGETS_WITH_E_BOX, LIAO_METASTASIS, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, YOSHIMURA_MAPK8_TARGETS_UP, VECCHI_GASTRIC_CANCER_EARLY_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, PURBEY_TARGETS_OF_CTBP1_AND_SATB1_DN, chr8q24, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ELF2_TARGET_GENES, PCGF1_TARGET_GENES, RBM34_TARGET_GENES, SIX1_TARGET_GENES, SNIP1_TARGET_GENES

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), zinc ion binding (GO:0008270), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
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
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GLI4	LRRC24	Q50LG9	533
GLI4	MYCL	P12524	495
GLI4	C1orf216	Q8TAB5	479
GLI4	LRRC14	Q15048	463
GLI4	WDR97	A6NE52	453
GLI4	MYCN	P04198	440
GLI4	PHRF1	Q9P1Y6	420
GLI4	C1orf35	Q9BU76	417
GLI4	MYC	P01106	392
GLI4	STK36	Q9NRP7	390
GLI4	NRAS	P01111	388
GLI4	RBM4B	Q9BQ04	381
GLI4	LRRC23	Q53EV4	380
GLI4	RNF44	Q7L0R7	379
GLI4	HS6ST2	Q96MM7	374
GLI4	PTCH2	Q9Y6C5	374

IntAct

28 interactions, top by confidence:

A	B	Type	Score
GRN	GLI4	psi-mi:“MI:0915”(physical association)	0.560
WFS1	GLI4	psi-mi:“MI:0915”(physical association)	0.560
KIF1B	GLI4	psi-mi:“MI:0915”(physical association)	0.560
SPRED1	GLI4	psi-mi:“MI:0915”(physical association)	0.560
RETN	GLI4	psi-mi:“MI:0914”(association)	0.530
VTN	HAT1	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
K4.2	GLI4	psi-mi:“MI:0914”(association)	0.350
VTN	HAT1	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
LTBP2	ZNF320	psi-mi:“MI:0914”(association)	0.350
EFEMP1	ZNF316	psi-mi:“MI:0914”(association)	0.350
GLI4	ZNF316	psi-mi:“MI:0914”(association)	0.350
ADNP2	GLI4	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
YJU2B	ISY1-RAB43	psi-mi:“MI:0914”(association)	0.350
TRIM63	GLI4	psi-mi:“MI:0915”(physical association)	0.000
TRIM55	GLI4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (129): GLI4 (Affinity Capture-MS), GLI4 (Affinity Capture-MS), GLI4 (Affinity Capture-MS), GLI4 (Affinity Capture-MS), GLI4 (Two-hybrid), GLI4 (Two-hybrid), BMS1 (Affinity Capture-MS), SORL1 (Affinity Capture-MS), GLI4 (Affinity Capture-MS), ZNF397 (Affinity Capture-MS), ZNF791 (Affinity Capture-MS), LRP2 (Affinity Capture-MS), MTERF3 (Affinity Capture-MS), MRPS18B (Affinity Capture-MS), CENPB (Affinity Capture-MS)

ESM2 similar proteins: A2CE44, A6NFI3, A6NM28, A8K8V0, O15370, O70218, O95201, P0CJ78, P10075, P10754, P28698, P70338, Q04890, Q07120, Q14V87, Q19A40, Q569E7, Q58DK7, Q5DWN0, Q5FWU5, Q5RJR4, Q5T619, Q5TEC3, Q6DD87, Q6IQX8, Q6PD29, Q6PGE4, Q6ZMY9, Q7Z7K2, Q80VM4, Q8BIF9, Q8JZL0, Q8N8E2, Q8NAF0, Q8NCA9, Q8TD94, Q8WUU4, Q96C55, Q96H86, Q96MX3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

107 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1306 predictions. Top by Δscore:

Variant	Effect	Δscore
8:143267482:AAGGT:A	donor_loss	1.0000
8:143267483:AGG:A	donor_loss	1.0000
8:143267486:T:G	donor_loss	1.0000
8:143275082:G:GT	donor_gain	1.0000
8:143275083:A:T	donor_gain	1.0000
8:143267480:GGAAG:G	donor_gain	0.9900
8:143267481:GAAG:G	donor_gain	0.9900
8:143267481:GAAGG:G	donor_gain	0.9900
8:143267485:G:GG	donor_gain	0.9900
8:143266826:G:GT	donor_gain	0.9800
8:143274803:G:GG	donor_gain	0.9800
8:143274806:A:AG	donor_gain	0.9800
8:143274807:G:GG	donor_gain	0.9800
8:143275073:G:GG	donor_gain	0.9800
8:143274798:GCCCG:G	donor_gain	0.9700
8:143274802:GGT:G	donor_loss	0.9700
8:143274803:G:GC	donor_loss	0.9700
8:143274804:T:TC	donor_loss	0.9700
8:143267482:A:T	donor_gain	0.9600
8:143274805:GAGT:G	donor_loss	0.9600
8:143267483:AG:A	donor_gain	0.9500
8:143267484:GG:G	donor_gain	0.9500
8:143275891:TTTCA:T	acceptor_loss	0.9500
8:143275892:TTCA:T	acceptor_loss	0.9500
8:143275893:TCAG:T	acceptor_loss	0.9500
8:143275894:CAGAC:C	acceptor_loss	0.9500
8:143275895:A:AG	acceptor_gain	0.9500
8:143275895:A:C	acceptor_loss	0.9500
8:143275896:G:A	acceptor_loss	0.9500
8:143275896:G:GG	acceptor_gain	0.9500

AlphaMissense

2458 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:143276331:T:C	F220L	0.999
8:143276333:C:A	F220L	0.999
8:143276333:C:G	F220L	0.999
8:143276360:C:A	H229Q	0.999
8:143276360:C:G	H229Q	0.999
8:143276365:G:C	R231P	0.999
8:143276372:C:A	H233Q	0.999
8:143276372:C:G	H233Q	0.999
8:143276415:T:C	F248L	0.999
8:143276417:C:A	F248L	0.999
8:143276417:C:G	F248L	0.999
8:143276499:T:C	F276L	0.999
8:143276501:C:A	F276L	0.999
8:143276501:C:G	F276L	0.999
8:143276583:T:C	F304L	0.999
8:143276585:C:A	F304L	0.999
8:143276585:C:G	F304L	0.999
8:143276617:G:C	R315P	0.999
8:143276667:T:C	F332L	0.999
8:143276669:C:A	F332L	0.999
8:143276669:C:G	F332L	0.999
8:143276751:T:C	F360L	0.999
8:143276753:C:A	F360L	0.999
8:143276753:C:G	F360L	0.999
8:143276247:T:C	F192L	0.998
8:143276249:C:A	F192L	0.998
8:143276249:C:G	F192L	0.998
8:143276274:C:A	H201N	0.998
8:143276274:C:G	H201D	0.998
8:143276276:C:A	H201Q	0.998

dbSNP variants (sampled 300 via entrez): RS1000024007 (8:143270497 C>T), RS1000074700 (8:143270318 G>A), RS1000759240 (8:143271707 C>G,T), RS1000929052 (8:143265806 A>C), RS1001333794 (8:143272703 G>A), RS1001772442 (8:143267498 G>A,C,T), RS1001879918 (8:143267083 G>T), RS1002189737 (8:143276240 C>G), RS1002350943 (8:143266838 G>T), RS1002555570 (8:143268878 G>C), RS1002773502 (8:143271787 G>A), RS1003004446 (8:143271666 A>G), RS1003094657 (8:143273837 C>T), RS1003193129 (8:143277133 C>G), RS1003210903 (8:143275119 C>G)

Disease associations

OMIM: gene MIM:165280 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012227_45	Hip circumference adjusted for BMI	8.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bisphenol A	decreases methylation	1
aflatoxin B2	increases methylation	1
jinfukang	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Diazinon	increases methylation	1
Estradiol	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
Acrylamide	decreases expression	1
Particulate Matter	decreases expression	1

Cellosaurus cell lines

7 cell lines: 3 embryonic stem cell, 2 cancer cell line, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A2G9	SEES3-1V human GLI4, clone1	Embryonic stem cell	Male
CVCL_A2H0	SEES3-1V human GLI4, clone2	Embryonic stem cell	Male
CVCL_A2H1	SEES3-1V human GLI4, clone3	Embryonic stem cell	Male
CVCL_B1DJ	Abcam HCT 116 GLI4 KO	Cancer cell line	Male
CVCL_B2XR	Abcam HEK293T GLI4 KO	Transformed cell line	Female
CVCL_E1L3	HyCyte Hep-G2 KO-hGLI4	Cancer cell line	Male
CVCL_HC75	HEK293 eGFP-GLI4	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.