GBP5

Summary

GBP5 (guanylate binding protein 5, HGNC:19895) is a protein-coding gene on chromosome 1p22.2, encoding Guanylate-binding protein 5 (Q96PP8). Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens.

This gene belongs to the TRAFAC class dynamin-like GTPase superfamily. The encoded protein acts as an activator of NLRP3 inflammasome assembly and has a role in innate immunity and inflammation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 115362 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 104 total
• MANE Select transcript: NM_052942

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19895
Approved symbol	GBP5
Name	guanylate binding protein 5
Location	1p22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000154451
Ensembl biotype	protein_coding
OMIM	611467
Entrez	115362

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000370459, ENST00000443807, ENST00000471171, ENST00000481145, ENST00000490568, ENST00000866386, ENST00000866387, ENST00000866388, ENST00000866389

RefSeq mRNA: 3 — MANE Select: NM_052942 NM_001134486, NM_001391920, NM_052942

CCDS: CCDS722

Canonical transcript exons

ENST00000370459 — 12 exons

Exon	Start	End
ENSE00001016021	89262220	89262401
ENSE00001016026	89263736	89263948
ENSE00001016043	89266346	89266588
ENSE00001016061	89267417	89267526
ENSE00001067215	89266957	89267153
ENSE00001452769	89269366	89269574
ENSE00001452770	89270755	89270862
ENSE00001672512	89262683	89262785
ENSE00003537645	89268729	89268856
ENSE00003648440	89256189	89260817
ENSE00003681108	89264686	89264966
ENSE00003937466	89272452	89272860

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 97.99.

FANTOM5 (CAGE): breadth broad, TPM avg 23.3144 / max 1513.9312, expressed in 482 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13179	18.9878	424
13180	3.7798	373
13178	0.2161	61
13176	0.1007	44
13177	0.0920	42
13173	0.0777	35
13175	0.0351	11
13172	0.0251	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.99	gold quality
vermiform appendix	UBERON:0001154	97.07	gold quality
leukocyte	CL:0000738	94.29	gold quality
monocyte	CL:0000576	94.01	gold quality
blood	UBERON:0000178	93.08	gold quality
lymph node	UBERON:0000029	90.25	gold quality
spleen	UBERON:0002106	89.53	gold quality
caecum	UBERON:0001153	87.93	gold quality
bone marrow cell	CL:0002092	86.48	gold quality
gall bladder	UBERON:0002110	84.81	gold quality
bone marrow	UBERON:0002371	82.56	gold quality
right uterine tube	UBERON:0001302	82.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.68	gold quality
epithelium of nasopharynx	UBERON:0001951	81.66	gold quality
rectum	UBERON:0001052	80.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.39	gold quality
colonic epithelium	UBERON:0000397	77.93	gold quality
upper lobe of left lung	UBERON:0008952	77.68	gold quality
nasal cavity mucosa	UBERON:0001826	77.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.02	gold quality
upper lobe of lung	UBERON:0008948	76.43	gold quality
right lung	UBERON:0002167	76.30	gold quality
superficial temporal artery	UBERON:0001614	76.22	gold quality
smooth muscle tissue	UBERON:0001135	75.54	gold quality
tonsil	UBERON:0002372	75.50	gold quality
small intestine	UBERON:0002108	75.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.84	gold quality
nasal cavity epithelium	UBERON:0005384	73.65	silver quality
lung	UBERON:0002048	73.15	gold quality
palpebral conjunctiva	UBERON:0001812	72.87	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-120	yes	52.90
E-HCAD-8	yes	41.78
E-CURD-122	yes	27.96
E-ANND-3	yes	11.35
E-MTAB-9067	yes	4.04
E-MTAB-7606	no	616.75

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF1

miRNA regulators (miRDB)

71 targeting GBP5, 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-340-5P	100.00	72.50	4437
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-33A-3P	99.70	70.27	3362

Literature-anchored findings (GeneRIF, showing 25)

• Eight of nine melanoma cell lines expressed GBP-5a/b and four of nine additionally low levels of GBP-5ta. (PMID:15175044)
• GBP5 is constitutively localized in the Golgi apparatus of endothelial cells. (PMID:17266443)
• 3 genes were upregulated in patients with chronic EBV infection: guanylate binding protein 1, tumor necrosis factor-induced protein 6, and guanylate binding protein 5; they may be associated with the inflammatory reaction or with cell proliferation. (PMID:18260761)
• analysis of guanylate binding protein 5 and a tumor-specific truncated splice variant (PMID:20180847)
• The in vivo localization of GBP-5 at the Golgi apparatus is regulated by isoprenylation and dimerization. (PMID:21151871)
• guanylate binding protein 5 (GBP5) stimulates inflammasome assembly; GBP5 promoted selective NLRP3 inflammasome responses to pathogenic bacteria and soluble but not crystalline inflammasome priming agents; GBP5 serves as a unique rheostat for NLRP3 inflammasome activation (PMID:22461501)
• GZMA, GBP5 and CD64 genes show promise as a rapid diagnostic markers separating tuberculosis from other pulmonary diseases. (PMID:26025597)
• Antiviral activity requires Golgi localization of GBP5, but not its GTPase activity. (PMID:26996307)
• these results reveal that GBP5 inhibited influenza virus replication through the activation of IFN signaling and proinflammatory factors (PMID:28376501)
• Previously reported tetrameric and dimeric species of hGBP-1 and hGBP-5 were unmasked as dimers and monomers, respectively, with their shapes depending on both the bound nucleotide and the ionic strength of the solution. (PMID:28580591)
• GBP5 and KLF2 may be useful as a diagnostic tool for active tuberculosis, also the two-gene set may serve as surrogate biomarkers for monitoring tuberculosis therapy. (PMID:28941629)
• we identified that the LG domains of hGBP-1 and hGBP-5 build an interaction site within the hetero dimer. Our in vitro study provides mechanistic insights into the homomeric and heteromeric interactions of hGBP-1 and hGBP-5 and present useful strategies to characterise the hGBP network further. (PMID:29618166)
• the two top differentially expressed genes in our sample, IRF1 and GBP5, both have primary inflammation and immune functions, and were significantly negatively correlated with total scores on our self-report of anhedonia across all 48 subjects with cocaine-use disorder (PMID:30408130)
• Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins. (PMID:31091448)
• GBP5 Is an Interferon-Induced Inhibitor of Respiratory Syncytial Virus. (PMID:32796072)
• GBP5 drives malignancy of glioblastoma via the Src/ERK1/2/MMP3 pathway. (PMID:33608513)
• Regulation of Synovial Inflammation and Tissue Destruction by Guanylate Binding Protein 5 in Synovial Fibroblasts From Patients With Rheumatoid Arthritis and Rats With Adjuvant-Induced Arthritis. (PMID:33615742)
• Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins. (PMID:33876762)
• GBP5 promotes liver injury and inflammation by inducing hepatocyte apoptosis. (PMID:34958688)
• Whole blood GBP5 protein levels in patients with and without active tuberculosis. (PMID:35369870)
• Guanylate-binding protein 5-mediated cell-autonomous immunity suppresses inflammation in dental pulpitis: An in vitro study. (PMID:38050666)
• Guanylate binding protein 5 triggers NF-kappaB activation to foster radioresistance, metastatic progression and PD-L1 expression in oral squamous cell carcinoma. (PMID:38185269)
• Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice. (PMID:38531874)
• Guanylate binding protein 5 is an immune-related biomarker of oral squamous cell carcinoma: A retrospective prognostic study with bioinformatic analysis. (PMID:38978333)
• Guanylate-binding protein 5 antagonizes viral glycoproteins independently of furin processing. (PMID:39212413)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gbp5	ENSMUSG00000105504
rattus_norvegicus	Gbp5	ENSRNOG00000032240
drosophila_melanogaster	atl	FBGN0039213

Paralogs (10): GBP3 (ENSG00000117226), GBP1 (ENSG00000117228), ATL2 (ENSG00000119787), RNF112 (ENSG00000128482), GBP2 (ENSG00000162645), GBP4 (ENSG00000162654), GBP6 (ENSG00000183347), ATL3 (ENSG00000184743), ATL1 (ENSG00000198513), GBP7 (ENSG00000213512)

Protein

Protein identifiers

Guanylate-binding protein 5 — Q96PP8 (reviewed: Q96PP8)

Alternative names: GBP-TA antigen, GTP-binding protein 5, Guanine nucleotide-binding protein 5

All UniProt accessions (2): Q96PP8, E7ETN8

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, but in contrast to other family members, does not produce GMP. 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. As an activator of NLRP3 inflammasome assembly: promotes selective NLRP3 inflammasome assembly in response to microbial and soluble, but not crystalline, agents. Independently of its GTPase activity, acts as an inhibitor of various viruses infectivity, such as HIV-1, Zika and influenza A viruses, by inhibiting FURIN-mediated maturation of viral envelope proteins. Antigenic tumor-specific truncated splice form.

Subunit / interactions. Homodimer; homodimerizes upon GTP-binding, forming a close face-to-face dimer. Heterodimer with other family members, including GBP1, GBP2, GBP3 and GBP4. May also form tetramers (dimer of dimers) in the presence of GTP. Interacts with NLRP3, possibly in its tetrameric form, and promotes PYCARD/ASC polymerization. Homodimer; homodimerizes upon GTP-binding. GDP-bound form remains homodimeric. Homodimer; homodimerizes upon GTP-binding. GDP-bound is monomeric.

Subcellular location. Cytoplasmic vesicle membrane. Golgi apparatus membrane. Cytoplasm.

Tissue specificity. Expressed in peripheral blood monocytes (at protein level).

Post-translational modifications. Isoprenylation is required for proper subcellular location.

Induction. By IFNG in endothelial cells and in LPS-primed macrophages.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q96PP8-1	1, GBP-5a/b	yes
Q96PP8-2	2, GBP-5ta

RefSeq proteins (3): NP_001127958, NP_001378849, NP_443174* (*=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 (64 total): helix 20, strand 13, mutagenesis site 10, turn 5, binding site 4, region of interest 3, splice variant 2, sequence variant 2, chain 1, propeptide 1, modified residue 1, lipid moiety-binding region 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7CKF	X-RAY DIFFRACTION	2.28
7E5A	X-RAY DIFFRACTION	2.5
7E59	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PP8-F1	86.29	0.58

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 (4): 45–52; 67–69; 181–182; 245

Post-translational modifications (2): 583, 583

Mutagenesis-validated functional residues (10):

Position	Phenotype
51–52	loss of gtpase activity. no effect on tetramerization. does not affect ability to inhibit hiv-1 infectivity.
73	does not affect gtpase activity.
75	abolished gtpase activity, without affecting ability to inhibit hiv-1 infectivity.
137–141	promotes ubiquitination and degradation by s.flexneri ipah9.8.
182	decreased nucleotide-binding, without affecting ability to inhibit hiv-1 infectivity.
356	no effect.
417–421	in mmmd mutant; abolished dimerization and ability to restrict hiv-1; when associated with 464-a–a-476.
464–476	in mmmd mutant; abolished dimerization and ability to restrict hiv-1; when associated with 417-a–a-421.
583–586	loss of isoprenylation and of localization at the golgi apparatus.
583	loss of isoprenylation and of localization at the golgi apparatus. impaired ability to restrict hiv-1.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling
R-HSA-9953170	GBP-mediated host defense

MSigDB gene sets: 251 (showing top): GOBP_PROTEIN_HOMOTETRAMERIZATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_PROTEIN_TARGETING, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_INTERLEUKIN_1_PRODUCTION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM

GO Biological Process (25): activation of innate immune response (GO:0002218), protein targeting (GO:0006605), inflammatory response (GO:0006954), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of interleukin-18 production (GO:0032741), protein localization to Golgi apparatus (GO:0034067), defense response to bacterium (GO:0042742), positive regulation of innate immune response (GO:0045089), protein homotetramerization (GO:0051289), defense response to virus (GO:0051607), disruption of plasma membrane integrity in another organism (GO:0051673), cytolysis in another organism (GO:0051715), cellular response to lipopolysaccharide (GO:0071222), cellular response to type II interferon (GO:0071346), positive regulation of pyroptotic inflammatory response (GO:0140639), AIM2 inflammasome complex assembly (GO:0140970), positive regulation of AIM2 inflammasome complex assembly (GO:0140973), non-canonical inflammasome complex assembly (GO:0160075), positive regulation of cytokine production involved in inflammatory response (GO:1900017), positive regulation of NLRP3 inflammasome complex assembly (GO:1900227), immune system process (GO:0002376), response to bacterium (GO:0009617), innate immune response (GO:0045087), symbiont entry into host cell (GO:0046718), protein maturation (GO:0051604)

GO Molecular Function (9): GTPase activity (GO:0003924), GTP binding (GO:0005525), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), molecular function inhibitor activity (GO:0140678), nucleotide binding (GO:0000166), endopeptidase inhibitor activity (GO:0004866), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), perinuclear region of cytoplasm (GO:0048471), side of membrane (GO:0098552), symbiont cell surface (GO:0106139)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Interferon Signaling	1
Antimicrobial mechanism of IFN-stimulated genes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
defense response	3
cytoplasm	3
positive regulation of cytokine production	2
protein-containing complex assembly	2
positive regulation of protein-containing complex assembly	2
positive regulation of inflammasome-mediated signaling pathway	2
activation of immune response	1
positive regulation of innate immune response	1
establishment of protein localization	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
positive regulation of interleukin-1 production	1
interleukin-18 production	1
regulation of interleukin-18 production	1
protein localization to organelle	1
response to bacterium	1
positive regulation of response to biotic stimulus	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
innate immune response	1
regulation of innate immune response	1
positive regulation of immune response	1
protein homooligomerization	1
protein tetramerization	1
response to virus	1
disruption of cellular anatomical structure in another organism	1
cytolysis	1
killing of cells of another organism	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
response to type II interferon	1
cellular response to cytokine stimulus	1
positive regulation of inflammatory response	1
pyroptotic inflammatory response	1
AIM2 inflammasome complex assembly	1
regulation of AIM2 inflammasome complex assembly	1
cytokine production involved in inflammatory response	1

Protein interactions and networks

STRING

1452 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GBP5	NLRP3	Q96P20	763
GBP5	STAT1	P42224	654
GBP5	IFNG	P01579	631
GBP5	IL1B	P01584	577
GBP5	SERINC5	Q86VE9	552
GBP5	DUSP3	P51452	544
GBP5	WARS1	P23381	520
GBP5	IRF1	P10914	515
GBP5	D6RGC4	D6RGC4	507
GBP5	MX2	P20592	506
GBP5	FCGR1BP	Q92637	506
GBP5	AIM2	O14862	505
GBP5	TNF	P01375	493
GBP5	SLFN11	Q7Z7L1	486
GBP5	MX1	P20591	481

IntAct

42 interactions, top by confidence:

A	B	Type	Score
GBP5	GBP5	psi-mi:“MI:0915”(physical association)	0.760
GBP5	GBP5	psi-mi:“MI:0407”(direct interaction)	0.760
GBP5	GBP1	psi-mi:“MI:0914”(association)	0.720
GBP1	GBP5	psi-mi:“MI:0915”(physical association)	0.720
GBP5	GBP1	psi-mi:“MI:0915”(physical association)	0.720
GBP1	GBP2	psi-mi:“MI:0914”(association)	0.720
SLC22A16	APBA3	psi-mi:“MI:0914”(association)	0.530
GBP2	GBP5	psi-mi:“MI:0915”(physical association)	0.510
GBP5	GBP2	psi-mi:“MI:0915”(physical association)	0.510
GBP5	GBP3	psi-mi:“MI:0915”(physical association)	0.510
GBP5	GBP4	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (27): GBP5 (Two-hybrid), GBP5 (Affinity Capture-MS), GBP1 (Affinity Capture-MS), GBP5 (Affinity Capture-MS), ACSM1 (Affinity Capture-MS), C1orf159 (Affinity Capture-MS), APOL2 (Affinity Capture-MS), SURF1 (Affinity Capture-MS), EPHA4 (Affinity Capture-MS), GBP5 (Proximity Label-MS), GBP5 (Proximity Label-MS), GBP5 (Proximity Label-MS), GBP5 (Two-hybrid), SURF1 (Affinity Capture-MS), APOL2 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1403 predictions. Top by Δscore:

Variant	Effect	Δscore
1:89263945:GAGT:G	acceptor_gain	1.0000
1:89263946:AGT:A	acceptor_gain	1.0000
1:89263947:GT:G	acceptor_gain	1.0000
1:89263949:C:CC	acceptor_gain	1.0000
1:89263952:C:CT	acceptor_gain	1.0000
1:89263953:A:T	acceptor_gain	1.0000
1:89263967:CCA:C	acceptor_gain	1.0000
1:89263968:C:T	acceptor_gain	1.0000
1:89263968:CA:C	acceptor_gain	1.0000
1:89264717:T:TA	donor_gain	1.0000
1:89264718:C:A	donor_gain	1.0000
1:89264754:C:A	donor_gain	1.0000
1:89264761:A:AC	donor_gain	1.0000
1:89264762:C:CC	donor_gain	1.0000
1:89264963:AGAC:A	acceptor_gain	1.0000
1:89264964:GAC:G	acceptor_gain	1.0000
1:89264965:AC:A	acceptor_gain	1.0000
1:89264966:CC:C	acceptor_gain	1.0000
1:89264967:C:CC	acceptor_gain	1.0000
1:89264970:CA:C	acceptor_gain	1.0000
1:89264971:A:AC	acceptor_gain	1.0000
1:89264971:A:C	acceptor_gain	1.0000
1:89266338:ATACT:A	donor_loss	1.0000
1:89266340:AC:A	donor_loss	1.0000
1:89266342:TCACG:T	donor_loss	1.0000
1:89266343:CAC:C	donor_loss	1.0000
1:89266344:A:AC	donor_gain	1.0000
1:89266344:A:AT	donor_loss	1.0000
1:89266345:C:CA	donor_loss	1.0000
1:89266345:C:CC	donor_gain	1.0000

AlphaMissense

3903 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:89267476:G:C	S123R	0.981
1:89267476:G:T	S123R	0.981
1:89267478:T:G	S123R	0.981
1:89266434:A:C	F260L	0.973
1:89266434:A:T	F260L	0.973
1:89266436:A:G	F260L	0.973
1:89267050:A:G	W178R	0.973
1:89267050:A:T	W178R	0.973
1:89268852:G:C	F65L	0.969
1:89268852:G:T	F65L	0.969
1:89268854:A:G	F65L	0.969
1:89266512:A:C	F234L	0.961
1:89266512:A:T	F234L	0.961
1:89266514:A:G	F234L	0.961
1:89267473:G:C	S124R	0.961
1:89267473:G:T	S124R	0.961
1:89267475:T:G	S124R	0.961
1:89266380:C:A	K278N	0.953
1:89266380:C:G	K278N	0.953
1:89264963:A:G	L291P	0.951
1:89266413:G:C	F267L	0.949
1:89266413:G:T	F267L	0.949
1:89266415:A:G	F267L	0.949
1:89266530:A:C	F228L	0.949
1:89266530:A:T	F228L	0.949
1:89266532:A:G	F228L	0.949
1:89268766:A:T	V94D	0.939
1:89267033:G:C	F183L	0.936
1:89267033:G:T	F183L	0.936
1:89267035:A:G	F183L	0.936

dbSNP variants (sampled 300 via entrez): RS1000343350 (1:89255866 C>A,T), RS1000398039 (1:89257339 G>A), RS1000575270 (1:89269536 A>G,T), RS1000684012 (1:89268287 T>C), RS1000706017 (1:89261514 T>A), RS1000708527 (1:89255702 T>A,C,G), RS1000748786 (1:89261880 C>A), RS1000868670 (1:89264859 C>G,T), RS1000993816 (1:89267990 A>C), RS1001215890 (1:89271170 T>C), RS1001253996 (1:89256395 A>G), RS1001367904 (1:89264571 T>C), RS1001514824 (1:89270261 G>C), RS1001619274 (1:89257460 A>G), RS1001781034 (1:89263761 T>A,C)

Disease associations

OMIM: gene MIM:611467 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012490_238	Femur bone mineral density x serum urate levels interaction	7.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
afuresertib	increases expression	1
TL8-506	affects cotreatment, increases expression	1
bisphenol A	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
monomethylpropion	increases expression	1
cyanoginosin LR	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
beta-hydroxy simvastatin acid	decreases expression	1
abrine	increases expression	1
nabiximols	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	increases methylation	1
Copper	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Malathion	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F1NV	HyCyte GES-1 KO-hGBP5	Transformed cell line	Sex unspecified
CVCL_SP76	HAP1 GBP5 (-) 1	Cancer cell line	Male
CVCL_SP77	HAP1 GBP5 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice