GBP4

Summary

GBP4 (guanylate binding protein 4, HGNC:20480) is a protein-coding gene on chromosome 1p22.2, encoding Guanylate-binding protein 4 (Q96PP9). Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens.

Guanylate-binding proteins, such as GBP4, are induced by interferon and hydrolyze GTP to both GDP and GMP (Vestal, 2005 [PubMed 16108726]).

Source: NCBI Gene 115361 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 123 total
• MANE Select transcript: NM_052941

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20480
Approved symbol	GBP4
Name	guanylate binding protein 4
Location	1p22.2
Locus type	gene with protein product
Status	Approved
Aliases	Mpa2
Ensembl gene	ENSG00000162654
Ensembl biotype	protein_coding
OMIM	612466
Entrez	115361

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000355754, ENST00000471938, ENST00000481397, ENST00000953047

RefSeq mRNA: 1 — MANE Select: NM_052941 NM_052941

CCDS: CCDS721

Canonical transcript exons

ENST00000355754 — 11 exons

Exon	Start	End
ENSE00001067347	89197110	89197304
ENSE00001452773	89181144	89185469
ENSE00001452774	89198795	89198942
ENSE00001655812	89190038	89190318
ENSE00001685792	89191261	89191506
ENSE00001695644	89195297	89195424
ENSE00001701206	89193303	89193412
ENSE00001749172	89187000	89187102
ENSE00001787862	89188582	89188794
ENSE00001789723	89192904	89193100
ENSE00003624849	89186333	89186526

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 92.78.

FANTOM5 (CAGE): breadth broad, TPM avg 11.7316 / max 414.5083, expressed in 807 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13163	7.4489	753
13162	3.8460	497
13161	0.4367	125

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
leukocyte	CL:0000738	92.78	gold quality
monocyte	CL:0000576	92.70	gold quality
granulocyte	CL:0000094	92.58	gold quality
vermiform appendix	UBERON:0001154	91.50	gold quality
right lung	UBERON:0002167	91.40	gold quality
lymph node	UBERON:0000029	89.31	gold quality
colonic epithelium	UBERON:0000397	88.59	gold quality
upper lobe of left lung	UBERON:0008952	87.71	gold quality
spleen	UBERON:0002106	87.26	gold quality
caecum	UBERON:0001153	87.09	gold quality
upper lobe of lung	UBERON:0008948	86.91	gold quality
lung	UBERON:0002048	84.61	gold quality
apex of heart	UBERON:0002098	84.20	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.64	gold quality
blood	UBERON:0000178	82.62	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.47	gold quality
omental fat pad	UBERON:0010414	82.05	gold quality
peritoneum	UBERON:0002358	82.01	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.87	gold quality
calcaneal tendon	UBERON:0003701	81.83	gold quality
smooth muscle tissue	UBERON:0001135	81.76	gold quality
cardiac muscle of right atrium	UBERON:0003379	81.25	gold quality
gall bladder	UBERON:0002110	81.16	gold quality
adipose tissue	UBERON:0001013	81.03	gold quality
left ventricle myocardium	UBERON:0006566	80.79	silver quality
left ovary	UBERON:0002119	80.68	gold quality
right lobe of liver	UBERON:0001114	80.51	gold quality
ileal mucosa	UBERON:0000331	79.65	silver quality
metanephros cortex	UBERON:0010533	79.56	gold quality
tendon	UBERON:0000043	79.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	16.68
E-ANND-3	yes	10.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

116 targeting GBP4, 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-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093

Literature-anchored findings (GeneRIF, showing 1)

• Guanylate binding protein 4 shapes an inflamed tumor microenvironment and identifies immuno-hot tumors. (PMID:38347243)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gbp3	ENSMUSG00000028268
mus_musculus	Gbp7	ENSMUSG00000040253
rattus_norvegicus	Gbp4	ENSRNOG00000028768
rattus_norvegicus	Gbp7	ENSRNOG00000029191
rattus_norvegicus	Gbp6-ps2	ENSRNOG00000070399
drosophila_melanogaster	atl	FBGN0039213

Paralogs (10): GBP3 (ENSG00000117226), GBP1 (ENSG00000117228), ATL2 (ENSG00000119787), RNF112 (ENSG00000128482), GBP5 (ENSG00000154451), GBP2 (ENSG00000162645), GBP6 (ENSG00000183347), ATL3 (ENSG00000184743), ATL1 (ENSG00000198513), GBP7 (ENSG00000213512)

Protein

Protein identifiers

Guanylate-binding protein 4 — Q96PP9 (reviewed: Q96PP9)

Alternative names: GTP-binding protein 4, Guanine nucleotide-binding protein 4

All UniProt accessions (1): Q96PP9

UniProt curated annotations — full annotation on UniProt →

Function. Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens. Negatively regulates the antiviral response by inhibiting activation of IRF7 transcription factor.

Subunit / interactions. Heterodimer with other family members, including GBP1, GBP2 and GBP5. Dimerization regulates subcellular location. Interacts with IRF7; preventing interaction between TRAF6 and IRF7, resulting in impaired TRAF6-mediated IRF7 ubiquitination.

Subcellular location. Golgi apparatus membrane. Cytoplasm. Nucleus. Perinuclear region.

Post-translational modifications. (Microbial infection) Ubiquitinated by S.flexneri IpaH9.8, leading to its degradation by the proteasome, thereby preventing its ability to promote host defense against bacterial infection.

Induction. By IFNG during macrophage activation.

Similarity. Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.

RefSeq proteins (1): NP_443173* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003191	Guanylate-bd/ATL_C	Domain
IPR015894	Guanylate-bd_N	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030386	G_GB1_RHD3_dom	Domain
IPR036543	Guanylate-bd_C_sf	Homologous_superfamily
IPR037684	GBP_C	Domain

Pfam: PF02263, PF02841

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (25 total): sequence variant 10, sequence conflict 8, binding site 3, chain 1, domain 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PP9-F1	86.10	0.55

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 60–67; 82–84; 112–116

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling
R-HSA-9948001	CASP4 inflammasome assembly
R-HSA-9953170	GBP-mediated host defense
R-HSA-9956593	Enterobacterial factors antagonize host defense

MSigDB gene sets: 329 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, FOSTER_TOLERANT_MACROPHAGE_UP, GOBP_RESPONSE_TO_PROTOZOAN, MORI_SMALL_PRE_BII_LYMPHOCYTE_DN, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM, DODD_NASOPHARYNGEAL_CARCINOMA_UP, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, GOBP_RESPONSE_TO_TYPE_II_INTERFERON, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM

GO Biological Process (5): defense response to protozoan (GO:0042832), defense response to Gram-positive bacterium (GO:0050830), cellular response to type II interferon (GO:0071346), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (7): GTPase activity (GO:0003924), GTP binding (GO:0005525), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): Golgi membrane (GO:0000139), nucleus (GO:0005634), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Interferon Signaling	1
Non-canonical inflammasome activation	1
Antimicrobial mechanism of IFN-stimulated genes	1
Infection with Enterobacteria	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	4
intracellular membrane-bounded organelle	2
response to protozoan	1
defense response to other organism	1
defense response to bacterium	1
response to type II interferon	1
cellular response to cytokine stimulus	1
biological_process	1
immune response	1
defense response to symbiont	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
endomembrane system	1
membrane	1
cell periphery	1
intracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1016 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GBP4	GBP2	P32456	620
GBP4	IRF7	Q92985	595
GBP4	IFNG	P01579	526
GBP4	IFIT3	O14879	519
GBP4	IFIT2	P09913	505
GBP4	CIITA	P33076	462
GBP4	MX1	P20591	455
GBP4	RSAD2	Q8WXG1	454
GBP4	ISG15	P05161	451
GBP4	IL1B	P01584	448
GBP4	OASL	Q15646	447
GBP4	OAS2	P29728	447
GBP4	IFIT1	P09914	446
GBP4	IRF1	P10914	444
GBP4	IRF4	Q15306	431

IntAct

10 interactions, top by confidence:

A	B	Type	Score
GBP4	GBP4	psi-mi:“MI:0915”(physical association)	0.510
GBP1	GBP4	psi-mi:“MI:0915”(physical association)	0.510
GBP2	GBP4	psi-mi:“MI:0915”(physical association)	0.510
GBP5	GBP4	psi-mi:“MI:0915”(physical association)	0.510
GBP4	PNPT1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (3): GBP4 (Proximity Label-MS), GBP4 (Cross-Linking-MS (XL-MS)), GBP4 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0G2JDV3, A0MWD1, A1E2I4, A4UUI3, A6QQL3, A7VK00, B0BNF1, B0KWP7, B1H120, B1MTN8, B2KIE9, B3GNI6, B5FW69, P20591, P20592, P32455, P32456, Q01514, Q0VCP4, Q14141, Q1MT80, Q28379, Q2KTC2, Q3SZN0, Q4R555, Q5D1D6, Q5I2P5, Q5R5G3, Q5R9T9, Q5RBE1, Q61107, Q63663, Q642H3, Q6AXA6, Q6IRQ5, Q6ZN66, Q6ZU15, Q8C1B7, Q8C650, Q8CFB4

Diamond homologs: A0A0G2JDV3, A4UUI3, P32455, P32456, Q01514, Q1MT80, Q5D1D6, Q5R9T9, Q5RBE1, Q61107, Q63663, Q6ZN66, Q8CFB4, Q8N8V2, Q91Z40, Q96PP8, Q96PP9, Q9H0R5, Q9Z0E6, A0E2L1, B6K0N7, P0CQ46, P0CQ47, A5DB26, Q4PEQ0, Q525S7, Q9UTE0, A0A386CAB9, Q9P5X6, C4JQN4, Q6BK59

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1671 predictions. Top by Δscore:

Variant	Effect	Δscore
1:89186328:CTCA:C	donor_loss	1.0000
1:89186329:TCA:T	donor_loss	1.0000
1:89186330:CACCT:C	donor_loss	1.0000
1:89186331:ACCT:A	donor_loss	1.0000
1:89186332:C:CA	donor_loss	1.0000
1:89186522:CTCCG:C	acceptor_gain	1.0000
1:89186523:TCCG:T	acceptor_gain	1.0000
1:89186524:CCG:C	acceptor_gain	1.0000
1:89186524:CCGC:C	acceptor_gain	1.0000
1:89186525:CG:C	acceptor_gain	1.0000
1:89186525:CGC:C	acceptor_gain	1.0000
1:89186527:C:CC	acceptor_gain	1.0000
1:89186533:C:CT	acceptor_gain	1.0000
1:89186533:C:T	acceptor_gain	1.0000
1:89186535:C:CT	acceptor_gain	1.0000
1:89186536:A:T	acceptor_gain	1.0000
1:89186540:G:C	acceptor_gain	1.0000
1:89186540:G:GC	acceptor_gain	1.0000
1:89186541:T:C	acceptor_gain	1.0000
1:89186541:T:TC	acceptor_gain	1.0000
1:89186542:T:C	acceptor_gain	1.0000
1:89186542:T:TC	acceptor_gain	1.0000
1:89186543:T:C	acceptor_gain	1.0000
1:89186543:T:TC	acceptor_gain	1.0000
1:89186994:CTGTA:C	donor_loss	1.0000
1:89186995:TGTAC:T	donor_loss	1.0000
1:89186996:GTACC:G	donor_loss	1.0000
1:89186997:TACCT:T	donor_loss	1.0000
1:89186998:A:AG	donor_loss	1.0000
1:89187103:C:CC	acceptor_gain	1.0000

AlphaMissense

4237 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:89195420:G:C	F80L	0.974
1:89195420:G:T	F80L	0.974
1:89195422:A:G	F80L	0.974
1:89197148:T:A	K66I	0.974
1:89191430:A:C	F249L	0.960
1:89191430:A:T	F249L	0.960
1:89191432:A:G	F249L	0.960
1:89191349:G:C	F276L	0.957
1:89191349:G:T	F276L	0.957
1:89191351:A:G	F276L	0.957
1:89192997:A:G	W193R	0.949
1:89192997:A:T	W193R	0.949
1:89192980:A:C	F198L	0.948
1:89192980:A:T	F198L	0.948
1:89192982:A:G	F198L	0.948
1:89193359:G:C	S139R	0.944
1:89193359:G:T	S139R	0.944
1:89193361:T:G	S139R	0.944
1:89193362:G:C	S138R	0.944
1:89193362:G:T	S138R	0.944
1:89193364:T:G	S138R	0.944
1:89190089:G:C	F382L	0.942
1:89190089:G:T	F382L	0.942
1:89190091:A:G	F382L	0.942
1:89190103:C:G	A378P	0.935
1:89191328:G:C	F283L	0.933
1:89191328:G:T	F283L	0.933
1:89191330:A:G	F283L	0.933
1:89197148:T:G	K66T	0.933
1:89193383:A:C	F131L	0.922

dbSNP variants (sampled 300 via entrez): RS1000354273 (1:89200152 T>C), RS1000483885 (1:89193320 C>G), RS1000619580 (1:89182171 G>A,T), RS1000923684 (1:89199910 C>T), RS1001095737 (1:89186837 A>C), RS1001155850 (1:89193646 A>G), RS1001177578 (1:89189471 G>A), RS1001201645 (1:89196397 G>T), RS1001313485 (1:89189816 G>A), RS1001478782 (1:89182732 G>A), RS1001604732 (1:89187799 AT>A), RS1001773490 (1:89181126 A>G), RS1001952110 (1:89188101 C>G), RS1002154573 (1:89194960 C>T), RS1002415828 (1:89192735 T>C)

Disease associations

OMIM: gene MIM:612466 | 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
GCST012490_267	Femur bone mineral density x serum urate levels interaction	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases expression	3
Acetaminophen	decreases expression, increases expression	3
Nickel	decreases expression, increases expression	3
Benzo(a)pyrene	decreases methylation, increases mutagenesis	2
Tretinoin	increases expression	2
afuresertib	increases expression	1
TL8-506	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
gallium arsenide	decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	decreases expression	1
beta-hydroxy simvastatin acid	decreases expression	1
ICG 001	increases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Benzoates	decreases expression	1
Copper	affects binding, increases expression	1
Cytarabine	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1FD	Abcam A-549 GBP4 KO 1	Cancer cell line	Male
CVCL_B2MX	Abcam A-549 GBP4 KO 2	Cancer cell line	Male

Clinical trials (associated diseases)

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