GBP6

Summary

GBP6 (guanylate binding protein family member 6, HGNC:25395) is a protein-coding gene on chromosome 1p22.2, encoding Guanylate-binding protein 6 (Q6ZN66). Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens, such as bacterial pathogens Listeria monocytogenes and Mycobacterium bovis BCG as well as the protozoan pathogen Toxoplasma gondii.

Guanylate-binding proteins, such as GBP6, are induced by interferon and hydrolyze GTP to both GDP and GMP (Olszewski et al., 2006 [PubMed 16689661]).

Source: NCBI Gene 163351 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 110 total
• MANE Select transcript: NM_198460

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25395
Approved symbol	GBP6
Name	guanylate binding protein family member 6
Location	1p22.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp686G0786
Ensembl gene	ENSG00000183347
Ensembl biotype	protein_coding
OMIM	612467
Entrez	163351

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000370456, ENST00000869870

RefSeq mRNA: 2 — MANE Select: NM_198460 NM_001320257, NM_198460

CCDS: CCDS723

Canonical transcript exons

ENST00000370456 — 11 exons

Exon	Start	End
ENSE00001295636	89380386	89380631
ENSE00001312123	89378417	89378613
ENSE00001319727	89382664	89382876
ENSE00001334270	89364059	89364127
ENSE00001452761	89385230	89388160
ENSE00001452763	89368529	89368741
ENSE00001631244	89381694	89381974
ENSE00001719604	89383652	89383754
ENSE00001804822	89369546	89369673
ENSE00002399499	89384093	89384286
ENSE00003571949	89378103	89378212

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 98.79.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0385 / max 299.5281, expressed in 91 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3955	0.5969	27
3953	0.4085	89
3954	0.0331	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	98.79	gold quality
gingiva	UBERON:0001828	98.76	gold quality
pharyngeal mucosa	UBERON:0000355	98.59	gold quality
oral cavity	UBERON:0000167	97.97	gold quality
esophagus mucosa	UBERON:0002469	97.55	gold quality
esophagus squamous epithelium	UBERON:0006920	97.37	gold quality
lower esophagus mucosa	UBERON:0035834	97.13	gold quality
body of tongue	UBERON:0011876	95.15	gold quality
tongue	UBERON:0001723	90.15	gold quality
superior surface of tongue	UBERON:0007371	84.17	gold quality
epithelium of nasopharynx	UBERON:0001951	80.83	gold quality
tonsil	UBERON:0002372	79.39	gold quality
mammalian vulva	UBERON:0000997	78.63	gold quality
vagina	UBERON:0000996	77.39	gold quality
penis	UBERON:0000989	75.46	gold quality
bronchial epithelial cell	CL:0002328	74.76	gold quality
bronchus	UBERON:0002185	73.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.91	gold quality
esophagus	UBERON:0001043	71.22	gold quality
mouth mucosa	UBERON:0003729	65.49	gold quality
minor salivary gland	UBERON:0001830	60.63	gold quality
nasal cavity mucosa	UBERON:0001826	58.24	gold quality
ectocervix	UBERON:0012249	57.88	gold quality
saliva-secreting gland	UBERON:0001044	56.56	gold quality
uterine cervix	UBERON:0000002	55.84	gold quality
endothelial cell	CL:0000115	55.11	gold quality
lower lobe of lung	UBERON:0008949	53.77	silver quality
upper leg skin	UBERON:0004262	50.92	silver quality
right coronary artery	UBERON:0001625	50.53	gold quality
gall bladder	UBERON:0002110	49.25	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	512.00
E-ANND-3	yes	22.71
E-MTAB-6058	no	24.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

97 targeting GBP6, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-7978	99.86	66.90	856
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000110616
mus_musculus	Gbp9	ENSMUSG00000029298
mus_musculus	Gbp8	ENSMUSG00000034438
mus_musculus	Gbp4	ENSMUSG00000079363
mus_musculus	Gbp11	ENSMUSG00000092021
mus_musculus	Gbp6	ENSMUSG00000104713
mus_musculus	Gbp10	ENSMUSG00000105096
rattus_norvegicus	Gbp6-ps1	ENSRNOG00000002134
rattus_norvegicus		ENSRNOG00000066766
rattus_norvegicus	Gbp6	ENSRNOG00000068418
drosophila_melanogaster	atl	FBGN0039213

Paralogs (10): GBP3 (ENSG00000117226), GBP1 (ENSG00000117228), ATL2 (ENSG00000119787), RNF112 (ENSG00000128482), GBP5 (ENSG00000154451), GBP2 (ENSG00000162645), GBP4 (ENSG00000162654), ATL3 (ENSG00000184743), ATL1 (ENSG00000198513), GBP7 (ENSG00000213512)

Protein

Protein identifiers

Guanylate-binding protein 6 — Q6ZN66 (reviewed: Q6ZN66)

Alternative names: GTP-binding protein 6, Guanine nucleotide-binding protein 6

All UniProt accessions (1): Q6ZN66

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, such as bacterial pathogens Listeria monocytogenes and Mycobacterium bovis BCG as well as the protozoan pathogen Toxoplasma gondii. Confers protection to several pathogens, including the bacterial pathogens Listeria monocytogenes and Mycobacterium bovis BCG as well as the protozoan pathogen Toxoplasma gondii.

Subcellular location. Cytoplasmic vesicle.

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.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZN66-1	1	yes
Q6ZN66-2	2

RefSeq proteins (2): NP_001307186, NP_940862* (*=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 (14 total): sequence variant 5, binding site 3, sequence conflict 2, chain 1, domain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZN66-F1	89.45	0.72

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

2 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling
R-HSA-9956593	Enterobacterial factors antagonize host defense

MSigDB gene sets: 199 (showing top): 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, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM, AFFAR_YY1_TARGETS_UP, GOBP_RESPONSE_TO_TYPE_II_INTERFERON, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, chr1p22, IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM, GAVIN_FOXP3_TARGETS_CLUSTER_P4

GO Biological Process (7): immune response (GO:0006955), defense response to bacterium (GO:0042742), 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 (5): GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (2): cytoplasmic vesicle (GO:0031410), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Interferon Signaling	1
Infection with Enterobacteria	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune system process	1
response to stimulus	1
defense response	1
response to bacterium	1
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
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular vesicle	1
extracellular vesicle	1

Protein interactions and networks

STRING

568 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GBP6	OAS2	P29728	575
GBP6	IFNG	P01579	534
GBP6	CMPK2	Q5EBM0	510
GBP6	IFI44	Q8TCB0	509
GBP6	IL1B	P01584	478
GBP6	HERC6	Q8IVU3	466
GBP6	IRF7	Q92985	463
GBP6	CLEC4E	Q9ULY5	460
GBP6	PYHIN1	Q6K0P9	437
GBP6	IFIT3	O14879	419
GBP6	IFIT2	P09913	419
GBP6	TNF	P01375	408
GBP6	TRIM21	P19474	397
GBP6	DDX4	Q9NQI0	397
GBP6	IRGM	A1A4Y4	396

IntAct

18 interactions, top by confidence:

A	B	Type	Score
GBP6	GBP7	psi-mi:“MI:0914”(association)	0.560
GBP6	GBP7	psi-mi:“MI:0915”(physical association)	0.560
FRMD1	A2ML1	psi-mi:“MI:0914”(association)	0.530
GBP6	H1-5	psi-mi:“MI:0915”(physical association)	0.400
GBP6	H1-2	psi-mi:“MI:0915”(physical association)	0.400
GBP6	PLEC	psi-mi:“MI:0915”(physical association)	0.400
GBP6	DHX9	psi-mi:“MI:0915”(physical association)	0.400
GBP6	H1-1	psi-mi:“MI:0915”(physical association)	0.400
	AP3B1	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
SRRT	A2ML1	psi-mi:“MI:0914”(association)	0.350
HSF2	A2ML1	psi-mi:“MI:0914”(association)	0.350
STK11	A2ML1	psi-mi:“MI:0914”(association)	0.350
FNDC5	A2ML1	psi-mi:“MI:0914”(association)	0.350
RSRP1	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): GBP6 (Affinity Capture-MS), GBP7 (Affinity Capture-MS), SIRT5 (Affinity Capture-MS), GBP6 (Proximity Label-MS), GBP6 (Proximity Label-MS), GBP6 (Proximity Label-MS), GBP6 (Proximity Label-MS), GBP6 (Proximity Label-MS), GBP6 (Affinity Capture-MS), GBP6 (Affinity Capture-MS), GBP6 (Affinity Capture-MS), GBP6 (Affinity Capture-MS), GBP7 (Affinity Capture-MS), GBP6 (Affinity Capture-MS), GBP6 (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, A0A509AN59, A1CPP3, A1D2K1, A2QR20, A3LWM9, A4HK17, A4I7K1, A5DB26, A5E240, A5K168, A6R1D5, A6S544, A6ZP10, A7AT07, A7ERA6, A7TJY3, A8N5E5, A8QAN4, B0D0N9, B0XQZ0, B2B1M4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1208 predictions. Top by Δscore:

Variant	Effect	Δscore
1:89378101:AG:A	acceptor_gain	1.0000
1:89378102:GG:G	acceptor_gain	1.0000
1:89378102:GGGT:G	acceptor_gain	1.0000
1:89378611:AAGG:A	donor_loss	1.0000
1:89378613:GGTA:G	donor_loss	1.0000
1:89378614:G:T	donor_loss	1.0000
1:89380384:A:AG	acceptor_gain	1.0000
1:89380385:G:GG	acceptor_gain	1.0000
1:89380385:GGCA:G	acceptor_gain	1.0000
1:89380547:G:GT	donor_gain	1.0000
1:89380548:A:T	donor_gain	1.0000
1:89380607:G:T	donor_gain	1.0000
1:89380627:GAATC:G	donor_gain	1.0000
1:89380630:TC:T	donor_gain	1.0000
1:89380632:G:GG	donor_gain	1.0000
1:89381692:AGGTC:A	acceptor_loss	1.0000
1:89381693:G:GC	acceptor_loss	1.0000
1:89381942:G:GT	donor_gain	1.0000
1:89381954:G:GT	donor_gain	1.0000
1:89381965:G:GT	donor_gain	1.0000
1:89381975:G:GG	donor_gain	1.0000
1:89381975:GT:G	donor_loss	1.0000
1:89381976:T:A	donor_loss	1.0000
1:89382659:TGCA:T	acceptor_loss	1.0000
1:89382661:CA:C	acceptor_loss	1.0000
1:89382662:A:AG	acceptor_gain	1.0000
1:89382662:AG:A	acceptor_gain	1.0000
1:89382663:G:GA	acceptor_gain	1.0000
1:89382663:GG:G	acceptor_gain	1.0000
1:89382663:GGAA:G	acceptor_gain	1.0000

AlphaMissense

4216 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:89368703:A:T	K51I	0.994
1:89369548:T:C	F65L	0.989
1:89369550:C:A	F65L	0.989
1:89369550:C:G	F65L	0.989
1:89368703:A:C	K51T	0.983
1:89378520:T:A	W178R	0.983
1:89378520:T:C	W178R	0.983
1:89368702:A:C	K51Q	0.977
1:89368704:A:C	K51N	0.976
1:89368704:A:T	K51N	0.976
1:89369646:C:A	D97E	0.976
1:89369646:C:G	D97E	0.976
1:89378535:T:C	F183L	0.974
1:89378537:C:A	F183L	0.974
1:89378537:C:G	F183L	0.974
1:89380541:T:C	F261L	0.969
1:89380543:C:A	F261L	0.969
1:89380543:C:G	F261L	0.969
1:89369636:T:A	V94D	0.968
1:89369645:A:T	D97V	0.966
1:89381936:T:C	F372L	0.965
1:89381938:C:A	F372L	0.965
1:89381938:C:G	F372L	0.965
1:89378130:T:C	F116L	0.963
1:89378132:T:A	F116L	0.963
1:89378132:T:G	F116L	0.963
1:89380442:T:C	F228L	0.963
1:89380444:T:A	F228L	0.963
1:89380444:T:G	F228L	0.963
1:89381909:G:C	A363P	0.962

dbSNP variants (sampled 300 via entrez): RS1000003489 (1:89370234 G>A), RS1000006190 (1:89383131 T>C), RS1000071573 (1:89371437 C>T), RS1000097538 (1:89379354 G>T), RS1000150369 (1:89362770 T>A), RS1000199538 (1:89371334 A>G), RS1000367472 (1:89365359 G>A), RS1000374744 (1:89388061 T>C,G), RS1000554177 (1:89379685 C>A), RS1000857318 (1:89388246 C>T), RS1001160936 (1:89378018 A>C,G), RS1001191431 (1:89362500 G>A,C), RS1001235112 (1:89381064 C>A,T), RS1001258176 (1:89364184 A>T), RS1001265406 (1:89387742 G>A,C)

Disease associations

OMIM: gene MIM:612467 | 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)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs928655	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Rheumatoid arthritis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs928655	GBP6	3	0.00	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, increases expression	1
alpha phellandrene	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Furaldehyde	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lipopolysaccharides	affects response to substance, affects cotreatment, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Sodium Chloride	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Vincristine	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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