ARHGEF1 (Rho guanine nucleotide exchange factor 1)

Gene

• Entrez ID: 9138
• Gene name: Rho guanine nucleotide exchange factor 1
• Gene symbol: ARHGEF1
• Synonyms (NCBI Gene): GEF1, IMD62, LBCL2, LSC, P115-RHOGEF, SUB1.5
• Chromosome: 19
• Chromosome location: 19q13.2
• Summary: Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form complex with G proteins and stimulate Rho-dependent signals. Multipl

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1568815169	C>T	Pathogenic	Coding sequence variant, stop gained
rs1568822574	G>T	Pathogenic	Splice acceptor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT002695	hsa-miR-124-3p	Microarray	15685193
MIRT018227	hsa-miR-335-5p	Microarray	18185580
MIRT002695	hsa-miR-124-3p	Microarray	18668037
MIRT002695	hsa-miR-124-3p	Microarray	15685193
MIRT050115	hsa-miR-26a-5p	CLASH	23622248
MIRT043573	hsa-miR-331-3p	CLASH	23622248
MIRT043573	hsa-miR-331-3p	CLASH	23622248
MIRT795503	hsa-miR-124	CLIP-seq
MIRT795504	hsa-miR-1275	CLIP-seq
MIRT795505	hsa-miR-3127-5p	CLIP-seq
MIRT795506	hsa-miR-3163	CLIP-seq
MIRT795507	hsa-miR-3614-5p	CLIP-seq
MIRT795508	hsa-miR-4665-5p	CLIP-seq
MIRT795509	hsa-miR-506	CLIP-seq
MIRT795510	hsa-miR-548ac	CLIP-seq
MIRT795511	hsa-miR-548ae	CLIP-seq
MIRT795512	hsa-miR-548aj	CLIP-seq
MIRT795513	hsa-miR-548am	CLIP-seq
MIRT795514	hsa-miR-548d-3p	CLIP-seq
MIRT795515	hsa-miR-548x	CLIP-seq
MIRT795516	hsa-miR-548z	CLIP-seq
MIRT2174670	hsa-miR-1273f	CLIP-seq
MIRT795504	hsa-miR-1275	CLIP-seq
MIRT795507	hsa-miR-3614-5p	CLIP-seq
MIRT2174671	hsa-miR-4447	CLIP-seq
MIRT2174672	hsa-miR-4472	CLIP-seq
MIRT2174673	hsa-miR-4651	CLIP-seq
MIRT795508	hsa-miR-4665-5p	CLIP-seq
MIRT2174674	hsa-miR-608	CLIP-seq
MIRT2174675	hsa-miR-663b	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
HOXA5	Activation	17379095
HOXA9	Activation	17379095

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001664	Function	G protein-coupled receptor binding	IBA
GO:0001664	Function	G protein-coupled receptor binding	IEA
GO:0003723	Function	RNA binding	HDA	22658674
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IBA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IDA	8810315, 9641916
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IEA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	TAS	8810315
GO:0005096	Function	GTPase activator activity	IEA
GO:0005515	Function	Protein binding	IPI	12681510, 20300064, 25416956
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	10747909
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	TAS	10747909
GO:0007186	Process	G protein-coupled receptor signaling pathway	IBA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
GO:0007266	Process	Rho protein signal transduction	TAS	10747909
GO:0016020	Component	Membrane	IEA
GO:0051056	Process	Regulation of small GTPase mediated signal transduction	IEA
GO:0051056	Process	Regulation of small GTPase mediated signal transduction	TAS
GO:0160221	Process	Rho-activating G protein-coupled receptor signaling pathway	IDA	9641916

Other IDs

• MIM: 601855
• HGNC: 681
• e!Ensembl: ENSG00000076928

Protein

• UniProt ID: Q92888
• Protein name: Rho guanine nucleotide exchange factor 1 (115 kDa guanine nucleotide exchange factor) (p115-RhoGEF) (p115RhoGEF) (Sub1.5)
• Protein function: Seems to play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13) subunits (PubMed:9641915, PubMed:9641916). Acts as a GTPase-activating protein (GAP) for GNA12 and GNA13, and as guanine nu
• PDB: 1IAP, 1SHZ, 3AB3, 3ODO, 3ODW, 3ODX, 3P6A
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF09128	RGS-like	42 → 232	Regulator of G protein signalling-like domain	Domain
  PF00621	RhoGEF	420 → 603	RhoGEF domain	Domain
  PF17838	PH_16	632 → 760	PH domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitously expressed. {ECO:0000269|PubMed:8810315, ECO:0000269|PubMed:9135076}.
• Sequence:

  MEDFARGAASPGPSRPGLVPVSIIGAEDEDFENELETNSEEQNSQFQSLEQVKRRPAHLM
  ALLQHVALQFEPGPLLCCLHADMLGSLGPKEAKKAFLDFYHSFLEKTAVLRVPVPPNVAF
  ELDRTRADLISEDVQRRFVQEVVQSQQVAVGRQLEDFRSKRLMGMTPWEQELAQLEAWVG
  RDRASYEARERHVAERLLMHLEEMQHTISTDEEKSAAVVNAIGLYMRHLGVRTKSGDKKS
  GRNFFRKKVMGNRRSDEPAKTKKGLSSILDAARWNRGEPQVPDFRHLKAEVDAEKPGATD
  RKGGVGMPSRDRNIGAPGQDTPGVSLHPLSLDSPDREPGADAPLELGDSSPQGPMSLESL
  APPESTDEGAETESPEPGDEGEPGRSGLELEPEEPPGWRELVPPDTLHSLPKSQVKRQEV
  ISELLVTEAAHVRMLRVLHDLFFQPMAECLFFPLEELQNIFPSLDELIEVHSLFLDRLMK
  RRQESGYLIEEIGDVLLARFDGAEGSWFQKISSRFCSRQSFALEQLKAKQRKDPRFCAFV
  QEAESRPRCRRLQLKDMIPTEMQRLTKYPLLLQSIGQNTEEPTEREKVELAAECCREILH
  HVNQAVRDMEDLLRLKDYQRRLDLSHLRQSSDPMLSEFKNLDITKKKLVHEGPLTWRVTK
  DKAVEVHVLLLDDLLLLLQRQDERLLLKSHSRTLTPTPDGKTMLRPVLRLTSAMTREVAT
  DHKAFYVLFTWDQEAQIYELVAQTVSERKNWCALITETAGSLKVPAPASRPKPRPSPSST
  REPLLSSSENGNGGRETSPADARTERILSDLLPFCRPGPEGQLAATALRKVLSLKQLLFP
  AEEDNGAGPPRDGDGVPGGGPLSPARTQEIQENLLSLEETMKQLEELEEEFCRLRPLLSQ
  LGGNSVPQPGCT

• Sequence length: 912

Pathways

KEGG:

Vascular smooth muscle contraction
Platelet activation
Regulation of actin cytoskeleton
Parathyroid hormone synthesis, secretion and action
Pathogenic Escherichia coli infection
Yersinia infection
Human cytomegalovirus infection
Pathways in cancer
Proteoglycans in cancer
Lipid and atherosclerosis

Reactome:

NRAGE signals death through JNK
Rho GTPase cycle
G alpha (12/13) signalling events

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ARHGEF1-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHILDHOOD-ONSET COMMON VARIABLE IMMUNODEFICIENCY DUE TO ARHGEF1 DEFICIENCY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Immunodeficiency 62	Uncertain significance; Conflicting classifications of pathogenicity; no classifications from unflagged records	ClinVar ClinGen, ClinVar, Disgenet, GWAS catalog, HPO ClinGen, ClinVar, Disgenet, GWAS catalog, HPO ClinGen, ClinVar, Disgenet, GWAS catalog, HPO	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Lung cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute lymphocytic leukemia	Lymphocytic Leukemia	BEFREE	30712246		★☆☆☆☆ Found in Text Mining only
Adenocarcinoma	Adenocarcinoma	BEFREE	2856251		★☆☆☆☆ Found in Text Mining only
Adrenal Gland Pheochromocytoma	Adrenal Gland Pheochromocytoma	BEFREE	26911374		★☆☆☆☆ Found in Text Mining only
Adult Acute Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	30712246		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic lateral sclerosis	Pubtator	25620680	Associate	★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	29130930		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	29071730		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	29130930		★☆☆☆☆ Found in Text Mining only
Bicuspid Aortic Valve Disease	Bicuspid aortic valve	Pubtator	36071494	Associate	★☆☆☆☆ Found in Text Mining only
Blast Phase	Blast phase chronic myelogenous leukemia	BEFREE	19074122		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	12748184		★☆☆☆☆ Found in Text Mining only
Bronchiectasis	Bronchiectasis	BEFREE	30521495		★☆☆☆☆ Found in Text Mining only
Bronchiectasis	Bronchiectasis	Pubtator	30521495	Associate	★☆☆☆☆ Found in Text Mining only
Bronchiectasis	Bronchiectasis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	29130930		★☆☆☆☆ Found in Text Mining only
Childhood Acute Lymphoblastic Leukemia	Lymphoblastic Leukemia	BEFREE	30712246		★☆☆☆☆ Found in Text Mining only
Childhood Acute Myeloid Leukemia	Acute Myeloid Leukemia	BEFREE	30089916, 31645648		★☆☆☆☆ Found in Text Mining only
Chronic Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	28465529		★☆☆☆☆ Found in Text Mining only
Cirrhosis	Cirrhosis	BEFREE	26385087		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	31676071		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Congenital leukocyte adherence deficiency	Congenital Leukocyte Adherence Deficiency	BEFREE	18709451		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	34914033	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	30200077		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	30200077		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	30200077	Associate	★☆☆☆☆ Found in Text Mining only
End Stage Liver Disease	End Stage Liver Disease	BEFREE	26385087		★☆☆☆☆ Found in Text Mining only
Endometrial Carcinoma	Endometrial carcinoma	BEFREE	28947174		★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	BEFREE	26385087		★☆☆☆☆ Found in Text Mining only
Immune thrombocytopenic purpura	Immune Thrombocytopenic Purpura	HPO_DG			★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	15143072, 17339181, 26361793, 29290617		★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	30568170	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	11278453, 21177505, 29290617, 29921955, 30595549, 30740913, 31050834		★☆☆☆☆ Found in Text Mining only
Leukocyte adhesion deficiency type 1	Leukocyte adhesion deficiency	Pubtator	19234463	Associate	★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver Cirrhosis	BEFREE	26385087		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	12748184		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of endometrium	Endometrial Cancer	BEFREE	28947174		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	31676071		★☆☆☆☆ Found in Text Mining only
Myeloid Leukemia, Chronic	Myeloid Leukemia	BEFREE	26985855		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	10769720, 18037957, 23070684		★☆☆☆☆ Found in Text Mining only
Nephroblastoma	Nephroblastoma	BEFREE	24503937		★☆☆☆☆ Found in Text Mining only
Pelvic Organ Prolapse	Pelvic Organ Prolapse	BEFREE	29987345		★☆☆☆☆ Found in Text Mining only
Pheochromocytoma	Pheochromocytoma	BEFREE	26911374		★☆☆☆☆ Found in Text Mining only
Portal Hypertension	Portal Hypertension	BEFREE	26385087		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	18037957		★☆☆☆☆ Found in Text Mining only
Respiratory Tract Infections	Respiratory system infectious disease	Pubtator	30521495	Associate	★☆☆☆☆ Found in Text Mining only
Retinoblastoma	Retinoblastoma	BEFREE	2856251		★☆☆☆☆ Found in Text Mining only
secondary acute myeloid leukemia	Myeloid leukemia	BEFREE	27570067		★☆☆☆☆ Found in Text Mining only