GBP5

protein-coding

guanylate binding protein 5, the group of Guanylate binding proteins

Gene summary

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. [provided by RefSeq, Jan 2017]

MANE transcript

NM_052942.5

Inheritance

—

ClinVar variants

U:87B:10

Top phenotype

Neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr1:89,256,189-89,272,860

External References & Databases

Ensembl (ENSG00000154451)

Transcript & Mutation Effects

hg38 • Region Span ~16.7 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 GBP5 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 85

not providedTotal: 4

Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_052942.5. 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	2 clinvar		4
missense			81 clinvar	6 clinvar	2 clinvar	89
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	87	8	2	97

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_052942.5	RefSeq	NP_443174.1	10	MANE Select
ENST00000370459.8	Ensembl	ENSP00000359488.3	10	MANE Select
NM_001134486.4	RefSeq	NP_001127958.1	10	Standard
NM_001391920.1	RefSeq	NP_001378849.1	8	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 Signaling

Biological Process

inflammatory response
response to bacterium
protein localization to Golgi apparatus
positive regulation of innate immune response
interleukin-1 beta secretion

Molecular Function

GTPase activity
protein binding
GTP binding
identical protein binding
protein homodimerization activity

Cellular Component

Golgi membrane
cytoplasm
Golgi apparatus
membrane
cytoplasmic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343435
Coding exons: 10
Length: 13912
Individuals with no LoFs: 125616
Homozygous LoFs: 0
Heterozygous LoFs: 132
Defined: 125748
p: 0.000525

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.304	320	305	1.05	0.0000150	3888
Missense (PolyPhen)		74	77.622	0.95334		1054
Synonymous	-0.488	126	119	1.06	0.00000642	1085
Loss of Function	1.44	18	25.9	0.695	0.00000120	319

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0048	0.0029	notable
Latino/Admixed American	0.0016	0.0016	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.00029	0.00029	rare
Other	0.00049	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: As an activator of NLRP3 inflammasome assembly, plays a role in innate immunity and inflammation. Promotes selective NLRP3 inflammasome assembly in response to microbial and soluble, but not crystalline, agents (PubMed:22461501). Hydrolyzes GTP, but in contrast to other family members, does not produce GMP (PubMed:20180847). {ECO:0000269|PubMed:20180847, ECO:0000269|PubMed:22461501}.;

Intolerance Scores

LoFtool: 0.969
RVIS EVS: 0.53
RVIS percentile EVS: 81.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0102

Gene Damage Prediction

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