G3BP1

protein-coding

G3BP stress granule assembly factor 1, the group of RNA binding motif containing|Endoribonucleases

Gene summary

This gene encodes one of the DNA-unwinding enzymes which prefers partially unwound 3'-tailed substrates and can also unwind partial RNA/DNA and RNA/RNA duplexes in an ATP-dependent fashion. This enzyme is a member of the heterogeneous nuclear RNA-binding proteins and is also an element of the Ras signal transduction pathway. It binds specifically to the Ras-GTPase-activating protein by associating with its SH3 domain. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005754.3

Inheritance

—

ClinVar variants

P:2U:77

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr5:151,771,045-151,812,911

External References & Databases

Ensembl (ENSG00000145907)

Transcript & Mutation Effects

hg38 • Region Span ~41.9 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 G3BP1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 37

not providedTotal: 36

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005754.3. 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			1 clinvar			1
missense			61 clinvar			61
nonsense			1 clinvar			1
start loss						0
frameshift			5 clinvar			5
splice donor/acceptor (+/-2bp)		2 clinvar	9 clinvar			11
Total	0	2	77	0	0	79

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 99 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005754.3	RefSeq	NP_005745.1	11	MANE Select
ENST00000356245.8	Ensembl	ENSP00000348578.3	11	MANE Select
NM_198395.2	RefSeq	NP_938405.1	11	Standard
ENST00000394123.7	Ensembl	ENSP00000377681.3	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

Ras protein signal transduction
DNA duplex unwinding
stress granule assembly
negative regulation of canonical Wnt signaling pathway
nucleic acid phosphodiester bond hydrolysis

Molecular Function

DNA binding
RNA binding
mRNA binding
ATP-dependent DNA helicase activity
ATP-dependent RNA helicase activity

Cellular Component

nucleus
cytosol
focal adhesion
cytoplasmic stress granule
perikaryon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394123
Coding exons: 11
Length: 41741
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125746
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.86	182	268	0.680	0.0000145	3054
Missense (PolyPhen)		19	45.613	0.41655		580
Synonymous	0.0314	89	89.4	0.996	0.00000445	919
Loss of Function	3.48	8	27.8	0.288	0.00000177	282

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000069	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000066	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: ATP- and magnesium-dependent helicase (PubMed:9889278). Unwinds preferentially partial DNA and RNA duplexes having a 17 bp annealed portion and either a hanging 3' tail or hanging tails at both 5'- and 3'-ends (PubMed:9889278). Unwinds DNA/DNA, RNA/DNA, and RNA/RNA substrates with comparable efficiency (PubMed:9889278). Acts unidirectionally by moving in the 5' to 3' direction along the bound single-stranded DNA (PubMed:9889278). Phosphorylation-dependent sequence-specific endoribonuclease in vitro (PubMed:11604510). Cleaves exclusively between cytosine and adenine and cleaves MYC mRNA preferentially at the 3'-UTR (PubMed:11604510). May be a regulated effector of stress granule assembly (PubMed:12642610, PubMed:20180778). {ECO:0000269|PubMed:11604510, ECO:0000269|PubMed:12642610, ECO:0000269|PubMed:20180778, ECO:0000269|PubMed:9889278}.;

Recessive Scores

pRec: 0.163

Intolerance Scores

LoFtool: 0.714
RVIS EVS: -0.36
RVIS percentile EVS: 28.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.997

Gene Damage Prediction

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