ARHGAP8 Rho GTPase activating protein 8 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ARHGAP8provided by HGNC
Official Full Name: Rho GTPase activating protein 8provided by HGNC
Primary source: HGNC:HGNC:677
See related: Ensembl:ENSG00000241484 MIM:609405; AllianceGenome:HGNC:677
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PP610; BPGAP1
Summary: This gene encodes a member of the RHOGAP family. GAP (GTPase-activating) family proteins participate in signaling pathways that regulate cell processes involved in cytoskeletal changes. GAP proteins alternate between an active (GTP-bound) and inactive (GDP-bound) state based on the GTP:GDP ratio in the cell. This family member is a multidomain protein that functions to promote Erk activation and cell motility. Alternative splicing results in multiple transcript variants. Read-through transcripts from the upstream proline rich 5, renal (PRR5) gene into this gene also exist, which led to the original description of PRR5 and ARHGAP8 being a single gene. [provided by RefSeq, Nov 2010]
Expression: Broad expression in kidney (RPKM 6.0), thyroid (RPKM 5.9) and 18 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q13.31

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (44752575..44862784)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (45236322..45346305)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (45148455..45258664)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The scaffold RhoGAP protein ARHGAP8/BPGAP1 synchronizes Rac and Rho signaling to facilitate cell migration.
Title: The scaffold RhoGAP protein ARHGAP8/BPGAP1 synchronizes Rac and Rho signaling to facilitate cell migration.
Fusion protein PRR5-ARHGAP8 plays a role in bipolar disorder with binge eating behavior.
Title: Bipolar disorder with binge eating behavior: a genome-wide association study implicates PRR5-ARHGAP8.
BPGAP1 provides a crucial spatiotemporal checkpoint where JNK and MP1/MEK1 work in concert to regulate endosomal and nuclear ERK signaling in cell proliferation control.
Title: BPGAP1 spatially integrates JNK/ERK signaling crosstalk in oncogenesis.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Observational study of gene-disease association. (HuGE Navigator)
Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
Pin1 regulates BPGAP1 function in Rho and Erk signalling, with active Mek2 serving as a novel regulatory scaffold that promotes crosstalk between RhoGAP, Pin1 and Erk in the regulation of cell migration.
Title: Active Mek2 as a regulatory scaffold that promotes Pin1 binding to BPGAP1 to suppress BPGAP1-induced acute Erk activation and cell migration.
BPGAP1 has a role in regulating cell dynamics with BNIP-2 and Cdc42GAP homology/Sec14p-like, proline-rich, and GTPase-activating protein domains of BPGAP1
Title: Concerted regulation of cell dynamics by BNIP-2 and Cdc42GAP homology/Sec14p-like, proline-rich, and GTPase-activating protein domains of a novel Rho GTPase-activating protein, BPGAP1.
BPGAP1 is a novel RhoGAP that co-ordinately regulates pseudopodia and cell migration through the interplay of its BNIP-2 and Cdc42GAP homology domains.
Title: Filling the GAPs in cell dynamics control: BPGAP1 promotes cortactin translocation to the cell periphery for enhanced cell migration.
findings reveal a concomitant activation of endocytosis and ERK signaling by BPGAP1 via the coupling of its proline-rich region, which targets EEN and its functional GAP domain
Title: Activation of EGF receptor endocytosis and ERK1/2 signaling by BPGAP1 requires direct interaction with EEN/endophilin II and a functional RhoGAP domain.
ARHGAP8 expression was up-regulated in the majority of primary colorectal tumors analyzed in this work.
Title: ARHGAP8 is a novel member of the RHOGAP family related to ARHGAP1/CDC42GAP/p50RHOGAP: mutation and expression analyses in colorectal and breast cancers.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Bipolar disorder with comorbid binge eating history: A genome-wide association study implicates APOB. EBI GWAS Catalog EBI GWAS CatalogPubMed
Family-based genome-wide association study of frontal &#x003b8; oscillations identifies potassium channel gene KCNJ6. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D22S1168 (e-PCR), detects polymorphism
- UniSTS:33540

AL021655 (e-PCR)
- UniSTS:44042

SHGC-132331 (e-PCR)
- UniSTS:170780

AL008674 (e-PCR)
- UniSTS:14896

D8S2279 (e-PCR)
- UniSTS:473907

SHGC-85190 (e-PCR)
- UniSTS:104034

G65368 (e-PCR)
- UniSTS:166501

D1S1423 (e-PCR)
- UniSTS:149619

NoName (e-PCR)
- UniSTS:483700

AL021670 (e-PCR)
- UniSTS:38302

G49246 (e-PCR)
- UniSTS:109002

G49247 (e-PCR)
- UniSTS:109003

AL021650 (e-PCR)
- UniSTS:24018

Readthrough PRR5-ARHGAP8

Readthrough gene: PRR5-ARHGAP8, Included gene: PRR5

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTPase activator activity	IBA Inferred from Biological aspect of Ancestor more info
enables GTPase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables GTPase activator activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in negative regulation of endocytic recycling	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of small GTPase mediated signal transduction	TAS Traceable Author Statement more info
involved_in small GTPase-mediated signal transduction	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info

General protein information

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Preferred Names: rho GTPase-activating protein 8

Names: BCH domain-containing Cdc42GAP-like protein; BNIP-2 and Cdc42GAP homology domain-containing, proline-rich and Cdc42GAP-like protein subtype-1; rho-type GTPase-activating protein 8

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001017526.2 → NP_001017526.1 rho GTPase-activating protein 8 isoform 1

See identical proteins and their annotated locations for NP_001017526.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AK001306, AK022305, BC010490, Z83838

Consensus CDS

CCDS33664.1

UniProtKB/Swiss-Prot

A6ZJ79, A6ZJ80, P85298

UniProtKB/TrEMBL

Q86XV6, Q8IZM6

Related

ENSP00000374424.2, ENST00000389774.6

Conserved Domains (2) summary

cd00170
Location:12 → 188

SEC14; Sec14p-like lipid-binding domain. Found in secretory proteins, such as S. cerevisiae phosphatidylinositol transfer protein (Sec14p), and in lipid regulated proteins such as RhoGAPs, RhoGEFs and neurofibromin (NF1). SEC14 domain of Dbl is known to ...

cl02570
Location:222 → 412

RhoGAP; RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when ...
NM_001198726.2 → NP_001185655.1 rho GTPase-activating protein 8 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks both an alternate in-frame exon in the central coding region and an alternate exon that results in a frameshift in the 3' coding region, compared to variant 1. The encoded isoform (3) has a distinct C-terminus and is shorter than isoform 1.

Source sequence(s)

AI284954, AK001306, AW673723, BC067824

Consensus CDS

CCDS56233.1

UniProtKB/TrEMBL

Q6PCC7

Related

ENSP00000337287.4, ENST00000336963.8

Conserved Domains (2) summary

cd00170
Location:12 → 157

SEC14; Sec14p-like lipid-binding domain. Found in secretory proteins, such as S. cerevisiae phosphatidylinositol transfer protein (Sec14p), and in lipid regulated proteins such as RhoGAPs, RhoGEFs and neurofibromin (NF1). SEC14 domain of Dbl is known to ...

cl02570
Location:191 → 297

RhoGAP; RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when ...
NM_181335.3 → NP_851852.2 rho GTPase-activating protein 8 isoform 2

See identical proteins and their annotated locations for NP_851852.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the central coding reigon, compared to variant 1, resulting in an isoform (2) that is shorter than isoform 1.

Source sequence(s)

AK001306, AK022305, BC010490, Z83838

Consensus CDS

CCDS14060.2

UniProtKB/TrEMBL

Q86XV6, Q8IZM6

Related

ENSP00000348407.6, ENST00000356099.11

Conserved Domains (2) summary

cd00170
Location:12 → 157

SEC14; Sec14p-like lipid-binding domain. Found in secretory proteins, such as S. cerevisiae phosphatidylinositol transfer protein (Sec14p), and in lipid regulated proteins such as RhoGAPs, RhoGEFs and neurofibromin (NF1). SEC14 domain of Dbl is known to ...

cl02570
Location:191 → 381

RhoGAP; RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when ...