ARHGEF12 Rho guanine nucleotide exchange factor 12 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ARHGEF12provided by HGNC
Official Full Name: Rho guanine nucleotide exchange factor 12provided by HGNC
Primary source: HGNC:HGNC:14193
See related: Ensembl:ENSG00000196914 MIM:604763; AllianceGenome:HGNC:14193
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: LARG; PRO2792
Summary: Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli working through G protein-coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. This protein has been observed to form a myeloid/lymphoid fusion partner in acute myeloid leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]
Expression: Ubiquitous expression in kidney (RPKM 33.3), thyroid (RPKM 28.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q23.3

Exon count:: 43

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (120336413..120489937)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (120360067..120513690)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (120207122..120360646)

Chromosome 11 - NC_000011.10 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

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Targeting ARHGEF12 promotes neuroblastoma differentiation, MYCN degradation, and reduces tumorigenicity.
Title: Targeting ARHGEF12 promotes neuroblastoma differentiation, MYCN degradation, and reduces tumorigenicity.
ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor-induced leak.
Title: ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor-induced leak.
ARHGEF12 regulates erythropoiesis and is involved in erythroid regeneration after chemotherapy in acute lymphoblastic leukemia patients.
Title: ARHGEF12 regulates erythropoiesis and is involved in erythroid regeneration after chemotherapy in acute lymphoblastic leukemia patients.
Data show that phosphorylation of ribosomal protein S6 kinase 2 (RSK2) at threonine 577 is essential for leukemia-associated RhoGEF (LARG)-dependent Rho GTPase activation.
Title: RSK2 drives cell motility by serine phosphorylation of LARG and activation of Rho GTPases.
We studied the function of LARG in murine and human megakaryocytes and platelets with Larg knockout (KO), shRNA-mediated knockdown and small molecule-mediated inhibition. We found that LARG is important for human, but not murine, megakaryocyte maturation.
Title: Leukaemia-associated Rho guanine nucleotide exchange factor (LARG) plays an agonist specific role in platelet function through RhoA activation.
that leukemia-associated Rho guanine-nucleotide exchange factor can be directly phosphorylated by cyclin-dependent kinase 1
Title: Mitotic-dependent phosphorylation of leukemia-associated RhoGEF (LARG) by Cdk1.
Two related guanine nucleotide exchange factors (GEFs), PDZ-RhoGEF and leukemia-associated RhoGEF (LARG), use their PDZ domains to bind class B plexins and play critical roles in signaling.
Title: Secondary PDZ domain-binding site on class B plexins enhances the affinity for PDZ-RhoGEF.
this study identified a novel association between IOP and ARHGEF12.
Title: ARHGEF12 influences the risk of glaucoma by increasing intraocular pressure.
TGF-beta regulates LARG and GEF-H1 during epithelial-mesenchymal transition to affect stiffening response to force and cell invasion.
Title: TGF-β regulates LARG and GEF-H1 during EMT to affect stiffening response to force and cell invasion.
LARG is a novel and temporally distinct Rho Guanine Nucleotide Exchange Factor required for completion of abscission.
Title: Leukemia-associated RhoGEF (LARG) is a novel RhoGEF in cytokinesis and required for the proper completion of abscission.

Submit: New GeneRIF Correction See all GeneRIFs (33)

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
Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma. 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)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of Rho guanine nucleotide exchange factor 12 (ARHGEF12) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
retropepsin	gag-pol	HIV-1 PR is identified to have a physical interaction with Rho guanine nucleotide exchange factor (GEF) 12 (ARHGEF12) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

ha2836 (e-PCR)
- UniSTS:515599

SHGC-106833 (e-PCR)
- UniSTS:170011

RH17448 (e-PCR)
- UniSTS:33822

A009P33 (e-PCR)
- UniSTS:25380

G20457 (e-PCR)
- UniSTS:56624

A005R48 (e-PCR)
- UniSTS:56625

WI-21762 (e-PCR)
- UniSTS:5431

D11S2318E (e-PCR)
- UniSTS:29252

G32745 (e-PCR)
- UniSTS:117326

D11S4343 (e-PCR)
- UniSTS:154714

ARHGEF12_3798 (e-PCR)
- UniSTS:463234

G29223 (e-PCR)
- UniSTS:61321

RH92805 (e-PCR)
- UniSTS:84381

D11S4343 (e-PCR)
- UniSTS:34474

D11S4343 (e-PCR)
- UniSTS:34475

RH36486 (e-PCR)
- UniSTS:60603

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables G protein-coupled receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables G protein-coupled receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables GTPase activator activity	IEA Inferred from Electronic Annotation more info
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables guanyl-nucleotide exchange factor activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in Rho protein signal transduction	IEA Inferred from Electronic Annotation more info
involved_in regulation of small GTPase mediated signal transduction	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: rho guanine nucleotide exchange factor 12

Names: KMT2A/ARHGEF12 fusion protein; Rho guanine nucleotide exchange factor (GEF) 12; leukemia-associated RhoGEF; leukemia-associated rho guanine nucleotide exchange factor

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.

Genomic

NG_027960.1 RefSeqGene

Range

4505..158029

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001198665.2 → NP_001185594.1 rho guanine nucleotide exchange factor 12 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AF180681, AK304316, AP000758, AP001150, BC063117

Consensus CDS

CCDS55794.1

UniProtKB/TrEMBL

A0A2X0SFF5

Related

ENSP00000349056.3, ENST00000356641.7

Conserved Domains (4) summary

cd08754
Location:330 → 551

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

cd00992
Location:52 → 126

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:976 → 1113

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain

pfam00621
Location:772 → 957

RhoGEF; RhoGEF domain
NM_001301084.2 → NP_001288013.1 rho guanine nucleotide exchange factor 12 isoform 3

See identical proteins and their annotated locations for NP_001288013.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate first exon and initiates translation at a downstream AUG compared to variant 1. Thd resulting isoform (3) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AF180681, AP000659, AP000758, BX647785

Consensus CDS

CCDS76487.1

UniProtKB/TrEMBL

A0A2X0SFF5, E9PMR6

Related

ENSP00000432984.1, ENST00000532993.5

Conserved Domains (4) summary

cd08754
Location:246 → 467

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

cd00992
Location:2 → 42

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:892 → 1029

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain

pfam00621
Location:688 → 873

RhoGEF; RhoGEF domain
NM_015313.3 → NP_056128.1 rho guanine nucleotide exchange factor 12 isoform 1

See identical proteins and their annotated locations for NP_056128.1

Status: REVIEWED

Description

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

Source sequence(s)

AF180681, AK304316, AP000758, AP001150, BC063117

Consensus CDS

CCDS41727.1

UniProtKB/Swiss-Prot

O15086, Q6P526, Q9NZN5

UniProtKB/TrEMBL

A0A2X0SFF5

Related

ENSP00000380942.2, ENST00000397843.7

Conserved Domains (4) summary

cd08754
Location:349 → 570

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

cd00992
Location:71 → 145

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:995 → 1132

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain

pfam00621
Location:791 → 976

RhoGEF; RhoGEF domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

120336413..120489937

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006718805.4 → XP_006718868.1 rho guanine nucleotide exchange factor 12 isoform X1

UniProtKB/TrEMBL

A0A2X0SFF5

Conserved Domains (4) summary

cd08754
Location:324 → 545

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

cd00992
Location:71 → 145

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:970 → 1107

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain

pfam00621
Location:766 → 951

RhoGEF; RhoGEF domain
XM_047426659.1 → XP_047282615.1 rho guanine nucleotide exchange factor 12 isoform X2
XM_047426661.1 → XP_047282617.1 rho guanine nucleotide exchange factor 12 isoform X5
XM_047426660.1 → XP_047282616.1 rho guanine nucleotide exchange factor 12 isoform X3
XM_017017420.2 → XP_016872909.1 rho guanine nucleotide exchange factor 12 isoform X4

UniProtKB/TrEMBL

A0A2X0SFF5

Conserved Domains (4) summary

cd08754
Location:290 → 511

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

smart00325
Location:732 → 917

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd00992
Location:52 → 126

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:936 → 1073

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain
XM_047426662.1 → XP_047282618.1 rho guanine nucleotide exchange factor 12 isoform X7
XM_047426665.1 → XP_047282621.1 rho guanine nucleotide exchange factor 12 isoform X6

UniProtKB/TrEMBL

E9PMR6
XM_011542720.3 → XP_011541022.1 rho guanine nucleotide exchange factor 12 isoform X6

See identical proteins and their annotated locations for XP_011541022.1

UniProtKB/TrEMBL

A0A2X0SFF5, E9PMR6

Conserved Domains (4) summary

cd08754
Location:246 → 467

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

cd00992
Location:2 → 42

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:892 → 1029

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain

pfam00621
Location:688 → 873

RhoGEF; RhoGEF domain
XM_047426666.1 → XP_047282622.1 rho guanine nucleotide exchange factor 12 isoform X8
XM_047426663.1 → XP_047282619.1 rho guanine nucleotide exchange factor 12 isoform X6

UniProtKB/TrEMBL

E9PMR6
XM_047426667.1 → XP_047282623.1 rho guanine nucleotide exchange factor 12 isoform X9
XM_047426668.1 → XP_047282624.1 rho guanine nucleotide exchange factor 12 isoform X8
XM_017017421.2 → XP_016872910.1 rho guanine nucleotide exchange factor 12 isoform X6

UniProtKB/TrEMBL

A0A2X0SFF5, E9PMR6

Conserved Domains (4) summary

cd08754
Location:246 → 467

RGS_LARG; Regulator of G protein signaling (RGS) domain found in the leukemia-associated Rho guanine nucleotide exchange factor (RhoGEF) protein (LARG)

cd00992
Location:2 → 42

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd13390
Location:892 → 1029

PH_LARG; Leukemia-associated Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain

pfam00621
Location:688 → 873

RhoGEF; RhoGEF domain
XM_047426670.1 → XP_047282626.1 rho guanine nucleotide exchange factor 12 isoform X10
XM_047426664.1 → XP_047282620.1 rho guanine nucleotide exchange factor 12 isoform X6

UniProtKB/TrEMBL

E9PMR6
XM_047426669.1 → XP_047282625.1 rho guanine nucleotide exchange factor 12 isoform X8

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

120360067..120513690

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054368208.1 → XP_054224183.1 rho guanine nucleotide exchange factor 12 isoform X6

UniProtKB/TrEMBL

E9PMR6
XM_054368210.1 → XP_054224185.1 rho guanine nucleotide exchange factor 12 isoform X6

UniProtKB/TrEMBL

E9PMR6
XM_054368215.1 → XP_054224190.1 rho guanine nucleotide exchange factor 12 isoform X9
XM_054368214.1 → XP_054224189.1 rho guanine nucleotide exchange factor 12 isoform X8
XM_054368216.1 → XP_054224191.1 rho guanine nucleotide exchange factor 12 isoform X8
XM_054368203.1 → XP_054224178.1 rho guanine nucleotide exchange factor 12 isoform X1
XM_054368204.1 → XP_054224179.1 rho guanine nucleotide exchange factor 12 isoform X2
XM_054368207.1 → XP_054224182.1 rho guanine nucleotide exchange factor 12 isoform X5
XM_054368205.1 → XP_054224180.1 rho guanine nucleotide exchange factor 12 isoform X3
XM_054368206.1 → XP_054224181.1 rho guanine nucleotide exchange factor 12 isoform X4
XM_054368209.1 → XP_054224184.1 rho guanine nucleotide exchange factor 12 isoform X7
XM_054368213.1 → XP_054224188.1 rho guanine nucleotide exchange factor 12 isoform X6

UniProtKB/TrEMBL

E9PMR6
XM_054368212.1 → XP_054224187.1 rho guanine nucleotide exchange factor 12 isoform X6

UniProtKB/TrEMBL

E9PMR6
XM_054368218.1 → XP_054224193.1 rho guanine nucleotide exchange factor 12 isoform X10
XM_054368211.1 → XP_054224186.1 rho guanine nucleotide exchange factor 12 isoform X6

UniProtKB/TrEMBL

E9PMR6
XM_054368217.1 → XP_054224192.1 rho guanine nucleotide exchange factor 12 isoform X8