GBP7

Summary

GBP7 (guanylate binding protein 7, HGNC:29606) is a protein-coding gene on chromosome 1p22.2, encoding Guanylate-binding protein 7 (Q8N8V2). 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 GBP7, are induced by interferon and hydrolyze GTP to both GDP and GMP (Olszewski et al., 2006 [PubMed 16689661]).

Source: NCBI Gene 388646 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 107 total
• MANE Select transcript: NM_207398

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29606
Approved symbol	GBP7
Name	guanylate binding protein 7
Location	1p22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38822, GBP4L
Ensembl gene	ENSG00000213512
Ensembl biotype	protein_coding
OMIM	612468
Entrez	388646

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000294671, ENST00000650452, ENST00000897020, ENST00000897021, ENST00000897022, ENST00000897023, ENST00000897024

RefSeq mRNA: 1 — MANE Select: NM_207398 NM_207398

CCDS: CCDS720

Canonical transcript exons

ENST00000294671 — 11 exons

Exon	Start	End
ENSE00001067269	89133258	89133451
ENSE00001207603	89171746	89171954
ENSE00001242533	89131742	89132403
ENSE00001422103	89175921	89176003
ENSE00001607708	89150330	89150575
ENSE00001648770	89152268	89152464
ENSE00001671363	89164731	89164858
ENSE00001770189	89141546	89141648
ENSE00001778013	89152668	89152777
ENSE00003573253	89149292	89149572
ENSE00003621300	89147567	89147779

Expression profiles

Bgee: expression breadth broad, 41 present calls, max score 91.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0575 / max 30.6026, expressed in 7 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13159	0.0575	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	91.89	gold quality
liver	UBERON:0002107	91.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.62	gold quality
right adrenal gland	UBERON:0001233	59.84	gold quality
left adrenal gland	UBERON:0001234	58.17	gold quality
left adrenal gland cortex	UBERON:0035825	57.85	gold quality
right adrenal gland cortex	UBERON:0035827	57.40	gold quality
adrenal gland	UBERON:0002369	54.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	52.04	silver quality
cortical plate	UBERON:0005343	47.49	gold quality
gastrocnemius	UBERON:0001388	44.34	silver quality
muscle of leg	UBERON:0001383	44.13	silver quality
Brodmann (1909) area 9	UBERON:0013540	43.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	43.31	silver quality
sural nerve	UBERON:0015488	43.01	gold quality
prefrontal cortex	UBERON:0000451	42.83	gold quality
bone marrow cell	CL:0002092	42.71	gold quality
endometrium	UBERON:0001295	41.94	silver quality
cerebral cortex	UBERON:0000956	41.39	silver quality
frontal cortex	UBERON:0001870	41.32	silver quality
putamen	UBERON:0001874	40.54	silver quality
anterior cingulate cortex	UBERON:0009835	40.51	silver quality
right uterine tube	UBERON:0001302	40.02	silver quality
temporal lobe	UBERON:0001871	39.65	silver quality
hindlimb stylopod muscle	UBERON:0004252	39.60	gold quality
Ammon’s horn	UBERON:0001954	39.58	silver quality
amygdala	UBERON:0001876	39.49	silver quality
right frontal lobe	UBERON:0002810	39.02	silver quality
nucleus accumbens	UBERON:0001882	38.83	silver quality
caudate nucleus	UBERON:0001873	38.69	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting GBP7, 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-3646	100.00	73.56	5283
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-6512-5P	98.76	69.29	1195
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-6514-3P	97.52	66.50	808
HSA-MIR-335-5P	97.10	68.12	1022
HSA-MIR-2355-3P	96.84	68.54	909
HSA-MIR-610	96.84	67.98	905

Literature-anchored findings (GeneRIF, showing 1)

• Inducible Guanylate-Binding Protein 7 Facilitates Influenza A Virus Replication by Suppressing Innate Immunity via NF-kappaB and JAK-STAT Signaling Pathways. (PMID:33408175)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	atl	FBGN0039213

Paralogs (10): GBP3 (ENSG00000117226), GBP1 (ENSG00000117228), ATL2 (ENSG00000119787), RNF112 (ENSG00000128482), GBP5 (ENSG00000154451), GBP2 (ENSG00000162645), GBP4 (ENSG00000162654), GBP6 (ENSG00000183347), ATL3 (ENSG00000184743), ATL1 (ENSG00000198513)

Protein

Protein identifiers

Guanylate-binding protein 7 — Q8N8V2 (reviewed: Q8N8V2)

Alternative names: GTP-binding protein 7, Guanine nucleotide-binding protein 7, Guanylate-binding protein 4-like

All UniProt accessions (2): A0A3B3IRS3, Q8N8V2

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. Hydrolyzes GTP to GMP in two consecutive cleavage reactions and predominantly uses GTP and not GDP or GMP as the substrate. Following infection, recruited to the pathogen-containing vacuoles or vacuole-escaped bacteria and acts as a positive regulator of inflammasome assembly by promoting the release of inflammasome ligands from bacteria. Acts by promoting lysis of pathogen-containing vacuoles, releasing pathogens into the cytosol. Following pathogen release in the cytosol, promotes recruitment of proteins that mediate bacterial cytolysis: this liberates ligands that are detected by inflammasomes, such as lipopolysaccharide (LPS) that activates the non-canonical CASP4/CASP11 inflammasome or double-stranded DNA (dsDNA) that activates the AIM2 inflammasome. Also promotes IFN-gamma-mediated host defense against bacterial infections by regulating oxidative responses and bacteriolytic peptide generation. May help to assemble NADPH oxidase on phagosomal membranes by acting as a bridging protein between NADPH oxidase cytosolic subunits NCF2-NCF4 and the membrane subunits CYBA-CYBB. Participates along with GBP1 in trafficking monoubiquitinated protein cargo to autolysosomes for generating ubiquitin-derived antimicrobial peptides. Facilitates influenza A virus replication by inhibiting the activation of NF-kappaB and JAK-STAT signaling pathways and the expression of type I, type III interferons and pro-inflammatory cytokines. Confers protection to several pathogens, including the bacterial pathogens Listeria monocytogenes and Mycobacterium bovis BCG as well as the protozoan pathogen Toxoplasma gondii. Required for disruption of the parasitophorous vacuole formed following T.gondii infection and subsequent killing of the parasite.

Subunit / interactions. Monomer and dimer. Interacts with CYBA, CYBA-CYBB complex and ATG4B. Interacts (via GB1/RHD3-type G domain) with NCF2 and NCF2-NCF4 complex.

Subcellular location. Cytoplasmic vesicle membrane.

Induction. Up-regulated in response to influenza virus A infection.

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

RefSeq proteins (1): NP_997281* (*=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), 2 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)
• GDP + H2O = GMP + phosphate + H(+) (RHEA:22156)

UniProt features (10 total): region of interest 3, binding site 3, sequence variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N8V2-F1	86.64	0.53

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): 45–52; 67–69; 97–101

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling

MSigDB gene sets: 190 (showing top): REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_VIRAL_GENOME_REPLICATION, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_RESPONSE_TO_PROTOZOAN, GOBP_CYTOKINE_PRODUCTION, GOBP_VIRAL_GENOME_REPLICATION, GOBP_VIRAL_LIFE_CYCLE, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM, GOBP_DEFENSE_RESPONSE_TO_VIRUS

GO Biological Process (14): negative regulation of cytokine production (GO:0001818), negative regulation of type I interferon production (GO:0032480), negative regulation of type III interferon production (GO:0034345), defense response to bacterium (GO:0042742), defense response to protozoan (GO:0042832), regulation of canonical NF-kappaB signal transduction (GO:0043122), positive regulation of viral genome replication (GO:0045070), negative regulation of receptor signaling pathway via JAK-STAT (GO:0046426), defense response to Gram-positive bacterium (GO:0050830), defense response to virus (GO:0051607), cytolysis in another organism (GO:0051715), cellular response to type II interferon (GO:0071346), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (5): GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of cytokine production	2
defense response	2
cytokine production	1
regulation of cytokine production	1
negative regulation of gene expression	1
negative regulation of multicellular organismal process	1
regulation of type I interferon production	1
type I interferon production	1
type III interferon production	1
regulation of type III interferon production	1
response to bacterium	1
response to protozoan	1
defense response to other organism	1
canonical NF-kappaB signal transduction	1
regulation of intracellular signal transduction	1
viral genome replication	1
regulation of viral genome replication	1
positive regulation of viral process	1
cell surface receptor signaling pathway via JAK-STAT	1
regulation of receptor signaling pathway via JAK-STAT	1
negative regulation of receptor signaling pathway via STAT	1
defense response to bacterium	1
response to virus	1
cytolysis	1
killing of cells of another organism	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
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
vesicle membrane	1
cytoplasmic vesicle	1
cytoplasm	1

Protein interactions and networks

STRING

340 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GBP7	ATG4B	Q9Y4P1	732
GBP7	ATL1	Q8WXF7	610
GBP7	NCF2	P19878	519
GBP7	ISG15	P05161	514
GBP7	IFI44	Q8TCB0	502
GBP7	IFNG	P01579	498
GBP7	IRF9	Q00978	492
GBP7	RTP4	Q96DX8	491
GBP7	IL1B	P01584	484
GBP7	RSAD2	Q8WXG1	462
GBP7	PARP14	Q460N5	446
GBP7	HERC6	Q8IVU3	439
GBP7	GALNT15	Q8N3T1	425
GBP7	PARP9	Q8IXQ6	424
GBP7	IRGM	A1A4Y4	419

IntAct

13 interactions, top by confidence:

A	B	Type	Score
GBP6	GBP7	psi-mi:“MI:0914”(association)	0.560
PBX3	GBP7	psi-mi:“MI:0915”(physical association)	0.560
CPNE2	GBP7	psi-mi:“MI:0915”(physical association)	0.560
GBP7	PBX3	psi-mi:“MI:0915”(physical association)	0.560
GBP7	CPNE2	psi-mi:“MI:0915”(physical association)	0.560
GBP6	GBP7	psi-mi:“MI:0915”(physical association)	0.560
GBP2	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
GBP7	GOLGA4	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): GBP7 (Affinity Capture-MS), GBP7 (Affinity Capture-MS), GBP7 (Two-hybrid), GBP7 (Two-hybrid), GBP7 (Affinity Capture-MS), SYNE2 (Affinity Capture-MS), GBP7 (Affinity Capture-MS), GOLGA4 (Affinity Capture-MS), AUH (Cross-Linking-MS (XL-MS)), GBP7 (Cross-Linking-MS (XL-MS)), GBP7 (Affinity Capture-MS)

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

107 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	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1611 predictions. Top by Δscore:

Variant	Effect	Δscore
1:89133468:T:C	acceptor_gain	1.0000
1:89133468:T:TC	acceptor_gain	1.0000
1:89133471:C:CT	acceptor_gain	1.0000
1:89133472:A:T	acceptor_gain	1.0000
1:89147570:AACT:A	donor_gain	1.0000
1:89147676:T:A	donor_gain	1.0000
1:89147791:G:C	acceptor_gain	1.0000
1:89147791:G:GC	acceptor_gain	1.0000
1:89147793:G:C	acceptor_gain	1.0000
1:89149311:T:TA	donor_gain	1.0000
1:89149339:C:CA	donor_gain	1.0000
1:89149360:C:A	donor_gain	1.0000
1:89149591:T:C	acceptor_gain	1.0000
1:89149591:T:TC	acceptor_gain	1.0000
1:89152654:T:TA	donor_gain	1.0000
1:89152655:C:A	donor_gain	1.0000
1:89171741:CTCA:C	donor_loss	1.0000
1:89171743:CA:C	donor_loss	1.0000
1:89171745:C:A	donor_loss	1.0000
1:89171951:CTGT:C	acceptor_gain	1.0000
1:89171952:TGT:T	acceptor_gain	1.0000
1:89171955:C:CC	acceptor_gain	1.0000
1:89132404:C:CG	acceptor_loss	0.9900
1:89132405:T:G	acceptor_loss	0.9900
1:89133253:CTCA:C	donor_loss	0.9900
1:89133254:TCA:T	donor_loss	0.9900
1:89133255:CA:C	donor_loss	0.9900
1:89133256:A:T	donor_loss	0.9900
1:89133257:C:A	donor_loss	0.9900
1:89133461:CGAGG:C	acceptor_gain	0.9900

AlphaMissense

4231 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:89149343:G:C	F367L	0.947
1:89149343:G:T	F367L	0.947
1:89149345:A:G	F367L	0.947
1:89149307:A:C	F379L	0.936
1:89149307:A:T	F379L	0.936
1:89149309:A:G	F379L	0.936
1:89149357:C:G	A363P	0.934
1:89164854:G:C	F65L	0.932
1:89164854:G:T	F65L	0.932
1:89164856:A:G	F65L	0.932
1:89150499:A:C	F234L	0.923
1:89150499:A:T	F234L	0.923
1:89150501:A:G	F234L	0.923
1:89141625:G:C	F463L	0.917
1:89141625:G:T	F463L	0.917
1:89141627:A:G	F463L	0.917
1:89149328:G:C	F372L	0.889
1:89149328:G:T	F372L	0.889
1:89149330:A:G	F372L	0.889
1:89147654:G:C	F426L	0.884
1:89147654:G:T	F426L	0.884
1:89147656:A:G	F426L	0.884
1:89152344:A:C	F183L	0.882
1:89152344:A:T	F183L	0.882
1:89152346:A:G	F183L	0.882
1:89152361:A:G	W178R	0.882
1:89152361:A:T	W178R	0.882
1:89149456:C:G	A330P	0.875
1:89171784:T:A	K51I	0.875
1:89133331:A:G	L530P	0.859

dbSNP variants (sampled 300 via entrez): RS1000015130 (1:89168178 A>G), RS1000076647 (1:89145288 C>T), RS1000215124 (1:89161298 A>G), RS1000310604 (1:89174120 C>G,T), RS1000317964 (1:89155377 G>A), RS1000339428 (1:89168484 G>A), RS1000343733 (1:89175457 T>C), RS1000370184 (1:89155648 G>C), RS1000376850 (1:89139548 T>C), RS1000396239 (1:89175252 A>G), RS1000429109 (1:89139827 C>T), RS1000473738 (1:89148770 C>A,T), RS1000544833 (1:89131984 A>G), RS1000581834 (1:89141971 G>A), RS1000606534 (1:89133525 T>C)

Disease associations

OMIM: gene MIM:612468 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctane sulfonic acid	decreases expression	2
Benzo(a)pyrene	decreases expression, increases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
TL8-506	affects cotreatment, increases expression	1
methyleugenol	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Lipopolysaccharides	increases expression, decreases reaction	1
N-Nitrosopyrrolidine	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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