GBP2

protein-coding

guanylate binding protein 2, the group of Guanylate binding proteins

Gene summary

This gene belongs to the guanine-binding protein (GBP) family, which includes interferon-induced proteins that can bind to guanine nucleotides (GMP, GDP and GTP). The encoded protein is a GTPase which hydrolyzes GTP, predominantly to GDP. The protein may play a role as a marker of squamous cell carcinomas. [provided by RefSeq, Jul 2013]

MANE transcript

NM_004120.5

Inheritance

—

ClinVar variants

U:91B:8

Top phenotype

Inherited susceptibility to mycobacterial diseases

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr1:89,106,132-89,150,456

External References & Databases

Ensembl (ENSG00000162645)

Transcript & Mutation Effects

hg38 • Region Span ~44.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GBP2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 90

not providedTotal: 4

Inherited susceptibility to mycobacterial diseasesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004120.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	3 clinvar		5
missense			87 clinvar	5 clinvar		92
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	91	8	0	99

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004120.5	RefSeq	NP_004111.2	10	MANE Select
ENST00000370466.4	Ensembl	ENSP00000359497.3	10	MANE Select
ENST00000464839.5	Ensembl	ENSP00000434282.1	10	Standard
ENST00000875570.1	Ensembl	ENSP00000545629.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NOD-like receptor signaling pathway - Homo sapiens (human)
Cytokine Signaling in Immune system
Immune System
Interferon gamma signaling
Interferon alpha/beta signaling

Biological Process

immune response
protein localization to nucleus
interferon-gamma-mediated signaling pathway
type I interferon signaling pathway
cellular response to interferon-gamma

Molecular Function

GTPase activity
protein binding
GTP binding
protein homodimerization activity

Cellular Component

Golgi membrane
nucleus
nucleoplasm
cytoplasm
Golgi apparatus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370466
Coding exons: 10
Length: 44325
Individuals with no LoFs: 125672
Homozygous LoFs: 0
Heterozygous LoFs: 76
Defined: 125748
p: 0.000302

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.107	312	317	0.983	0.0000162	3918
Missense (PolyPhen)		85	95.611	0.88902		1251
Synonymous	-0.112	123	121	1.01	0.00000664	1084
Loss of Function	1.60	19	28.1	0.675	0.00000153	321

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00029	0.00029	rare
South Asian	0.00075	0.00075	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Hydrolyzes GTP to GMP in 2 consecutive cleavage reactions, but the major reaction product is GDP (PubMed:8706832). Exhibits antiviral activity against influenza virus. Promote oxidative killing and deliver antimicrobial peptides to autophagolysosomes, providing broad host protection against different pathogen classes (By similarity). {ECO:0000250|UniProtKB:P32455, ECO:0000269|PubMed:8706832}.;

Intolerance Scores

LoFtool: 0.875
RVIS EVS: 0.96
RVIS percentile EVS: 90.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.945

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium