ARHGEF28 (Rho guanine nucleotide exchange factor 28)

Gene

• Entrez ID: 64283
• Gene name: Rho guanine nucleotide exchange factor 28
• Gene symbol: ARHGEF28
• Synonyms (NCBI Gene): RGNEF, RIP2, p190RHOGEF
• Chromosome: 5
• Chromosome location: 5q13.2
• Summary: This gene encodes a member of the Rho guanine nucleotide exchange factor family. The encoded protein interacts with low molecular weight neurofilament mRNA and may be involved in the formation of amyotrophic lateral sclerosis neurofilament aggregates. Alt

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs188040167	G>A	Likely-benign, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT016811	hsa-miR-335-5p	Microarray	18185580
MIRT437514	hsa-miR-19b-3p	Immunoprecipitaion	22382630
MIRT495596	hsa-miR-6771-3p	PAR-CLIP	22291592
MIRT495595	hsa-miR-634	PAR-CLIP	22291592
MIRT495594	hsa-miR-1226-3p	PAR-CLIP	22291592
MIRT495593	hsa-miR-4310	PAR-CLIP	22291592
MIRT495592	hsa-miR-7157-5p	PAR-CLIP	22291592
MIRT495591	hsa-miR-338-3p	PAR-CLIP	22291592
MIRT495596	hsa-miR-6771-3p	PAR-CLIP	22291592
MIRT495595	hsa-miR-634	PAR-CLIP	22291592
MIRT495594	hsa-miR-1226-3p	PAR-CLIP	22291592
MIRT495593	hsa-miR-4310	PAR-CLIP	22291592
MIRT495592	hsa-miR-7157-5p	PAR-CLIP	22291592
MIRT495591	hsa-miR-338-3p	PAR-CLIP	22291592
MIRT444690	hsa-miR-7161-3p	PAR-CLIP	22100165
MIRT444689	hsa-miR-302a-5p	PAR-CLIP	22100165
MIRT444688	hsa-miR-4635	PAR-CLIP	22100165
MIRT444687	hsa-miR-203a-3p	PAR-CLIP	22100165
MIRT444690	hsa-miR-7161-3p	PAR-CLIP	22100165
MIRT444689	hsa-miR-302a-5p	PAR-CLIP	22100165
MIRT444688	hsa-miR-4635	PAR-CLIP	22100165
MIRT444687	hsa-miR-203a-3p	PAR-CLIP	22100165
MIRT495596	hsa-miR-6771-3p	PAR-CLIP	22291592
MIRT495595	hsa-miR-634	PAR-CLIP	22291592
MIRT495594	hsa-miR-1226-3p	PAR-CLIP	22291592
MIRT495593	hsa-miR-4310	PAR-CLIP	22291592
MIRT495592	hsa-miR-7157-5p	PAR-CLIP	22291592
MIRT495591	hsa-miR-338-3p	PAR-CLIP	22291592
MIRT495596	hsa-miR-6771-3p	PAR-CLIP	22291592
MIRT495595	hsa-miR-634	PAR-CLIP	22291592
MIRT495594	hsa-miR-1226-3p	PAR-CLIP	22291592
MIRT495593	hsa-miR-4310	PAR-CLIP	22291592
MIRT495592	hsa-miR-7157-5p	PAR-CLIP	22291592
MIRT495591	hsa-miR-338-3p	PAR-CLIP	22291592
MIRT444690	hsa-miR-7161-3p	PAR-CLIP	22100165
MIRT444689	hsa-miR-302a-5p	PAR-CLIP	22100165
MIRT444688	hsa-miR-4635	PAR-CLIP	22100165
MIRT444687	hsa-miR-203a-3p	PAR-CLIP	22100165
MIRT444690	hsa-miR-7161-3p	PAR-CLIP	22100165
MIRT444689	hsa-miR-302a-5p	PAR-CLIP	22100165
MIRT444688	hsa-miR-4635	PAR-CLIP	22100165
MIRT444687	hsa-miR-203a-3p	PAR-CLIP	22100165

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000902	Process	Cell morphogenesis	IBA
GO:0003723	Function	RNA binding	IEA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	EXP	11058585
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IEA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	TAS
GO:0005515	Function	Protein binding	IPI	32296183, 32814053
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0016020	Component	Membrane	IEA
GO:0021955	Process	Central nervous system neuron axonogenesis	IEA
GO:0030154	Process	Cell differentiation	IEA
GO:0035023	Process	Regulation of Rho protein signal transduction	IBA
GO:0046872	Function	Metal ion binding	IEA
GO:0048013	Process	Ephrin receptor signaling pathway	TAS
GO:0051056	Process	Regulation of small GTPase mediated signal transduction	TAS
GO:0060052	Process	Neurofilament cytoskeleton organization	IEA

Other IDs

• MIM: 612790
• HGNC: 30322
• e!Ensembl: ENSG00000214944

Protein

• UniProt ID: Q8N1W1
• Protein name: Rho guanine nucleotide exchange factor 28 (190 kDa guanine nucleotide exchange factor) (p190-RhoGEF) (p190RhoGEF) (Rho guanine nucleotide exchange factor)
• Protein function: Functions as a RHOA-specific guanine nucleotide exchange factor regulating signaling pathways downstream of integrins and growth factor receptors. Functions in axonal branching, synapse formation and dendritic morphogenesis. Also functions in fo
• PDB: 6BC0, 6BC1
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00130	C1_1	653 → 702	Phorbol esters/diacylglycerol binding domain (C1 domain)	Domain
  PF00621	RhoGEF	853 → 1042	RhoGEF domain	Domain
  PF17838	PH_16	1069 → 1188	PH domain	Domain

• Sequence:

  MELSCSEAPLYGQMMIYAKFDKNVYLPEDAEFYFTYDGSHQRHVMIAERIEDNVLQSSVP
  GHGLQETVTVSVCLCSEGYSPVTMGSGSVTYVDNMACRLARLLVTQANRLTACSHQTLLT
  PFALTAGALPALDEELVLALTHLELPLEWTVLGSSSLEVSSHRESLLHLAMRWGLAKLSQ
  FFLCLPGGVQALALPNEEGATPLDLALREGHSKLVEDVTNFQGRWSPSFSRVQLSEEASL
  HYIHSSETLTLTLNHTAEHLLEADIKLFRKYFWDRAFLVKAFEPEARPEERTAMPSSGAE
  TEEEIKNSVSSRSAAEKEDIKRVKSLVVQHNEHEDQHSLDLDRSFDILKKSKPPSTLLAA
  GRLSDMLNGGDEVYANCMVIDQVGDLDISYINIEGITATTSPESRGCTLWPQSSKHTLPT
  ETSPSVYPLSENVEGTAHTEAQQSFMSPSSSCASNLNLSFGWHGFEKEQSHLKKRSSSLD
  ALDADSEGEGHSEPSHICYTPGSQSSSRTGIPSGDELDSFETNTEPDFNISRAESLPLSS
  NLQSKESLLSGVRSRSYSCSSPKISLGKTRLVRELTVCSSSEEQRAYSLSEPPRENRIQE
  EEWDKYIIPAKSESEKYKVSRTFSFLMNRMTSPRNKSKTKSKDAKDKEKLNRHQFAPGTF
  SGVLQCLVCDKTLLGKESLQCSNCNANVHKGCKDAAPACTKKFQEKYNKNKPQTILGNSS
  FRDIPQPGLSLHPSSSVPVGLPTGRRETVGQVHPLSRSVPGTTLESFRRSATSLESESDH
  NSCRSRSHSDELLQSMGSSPSTESFIMEDVVDSSLWSDLSSDAQEFEAESWSLVVDPSFC
  NRQEKDVIKRQDVIFELMQTEMHHIQTLFIMSEIFRKGMKEELQLDHSTVDKIFPCLDEL
  LEIHRHFFYSMKERRQESCAGSDRNFVIDRIGDILVQQFSEENASKMKKIYGEFCCHHKE
  AVNLFKELQQNKKFQNFIKLRNSNLLARRRGIPECILLVTQRITKYPVLVERILQYTKER
  TEEHKDLRKALCLIKDMIATVDLKVNEYEKNQKWLEILNKIENKTYTKLKNGHVFRKQAL
  MSEERTLLYDGLVYWKTATGRFKDILALLLTDVLLFLQEKDQKYIFAAVDQKPSVISLQK
  LIAREVANEERGMFLISASSAGPEMYEIHTNSKEERNNWMRRIQQAVESCPEEKGGRTSE
  SDEDKRKAEARVAKIQQCQEILTNQDQQICAYLEEKLHIYAELGELSGFEDVHLEPHLLI
  KPDPGEPPQAASLLAAALKEAESLQVAVKASQMGAVSQSCEDSCGDSVLADTLSSHDVPG
  SPTASLVTGGREGRGCSDVDPGIQGVVTDLAVSDAGEKVECRNFPGSSQSEIIQAIQNLT
  RLLYSLQAALTIQDSHIEIHRLVLQQQEGLSLGHSILRGGPLQDQKSRDADRQHEELANV
  HQLQHQLQQEQRRWLRRCEQQQRAQATRESWLQERERECQSQEELLLRSRGELDLQLQEY
  QHSLERLREGQRLVEREQARMRAQQSLLGHWKHGRQRSLPAVLLPGGPEVMELNRSESLC
  HENSFFINEALVQMSFNTFNKLNPSVIHQDATYPTTQSHSDLVRTSEHQVDLKVDPSQPS
  NVSHKLWTAAGSGHQILPFHESSKDSCKNDLDTSHTESPTPHDSNSHRPQLQAFITEAKL
  NLPTRTMTRQDGETGDGAKENIVYL

• Sequence length: 1705

Pathways

KEGG:

Yersinia infection

Reactome:

EPHB-mediated forward signaling

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
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AMYOTROPHIC LATERAL SCLEROSIS	—	ClinGen, Disgenet, GenCC ClinGen, Disgenet, GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ARHGEF28-related disorder	Uncertain significance; Likely benign; Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASTROCYTOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CENTRAL NERVOUS SYSTEM CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC GRAFT VERSUS HOST DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC RETINOPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIVERTICULAR DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GALLSTONES	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOBLASTOMA MULTIFORME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEARING LOSS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HODGKINS LYMPHOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Meniere disease	Uncertain significance; Conflicting classifications of pathogenicity; Likely benign	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TREATMENT-RESISTANT HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	BEFREE	22835604, 23286752, 24712971, 28495450, 28969660, 30482479, 31060816		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	GENOMICS_ENGLAND_DG	27154192		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AMYOTROPHIC LATERAL SCLEROSIS 1	Lateral Sclerosis	BEFREE	23286752		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis, Familial	Amyotrophic lateral sclerosis	BEFREE	23286752		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis, Sporadic	Lateral Sclerosis	BEFREE	31060816		★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	21959219		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	BEFREE	17075290, 23794710		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Astrocytoma	Astrocytoma	BEFREE	29693188		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atherosclerosis	Atherosclerosis	BEFREE	21959219		★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	21236705, 30344914		★☆☆☆☆ Found in Text Mining only
Breast Cancer, Familial	Breast Cancer	BEFREE	16234258		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	24642040		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carcinoma of lung	Lung carcinoma	BEFREE	16691626		★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	31308489		★☆☆☆☆ Found in Text Mining only
Chronic Periodontitis	Periodontitis	BEFREE	22828789		★☆☆☆☆ Found in Text Mining only
Colitis	Colitis	BEFREE	23892723		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	21224360		★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic neoplasm	Pubtator	25922072	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	29358861	Associate	★☆☆☆☆ Found in Text Mining only
Crohn Disease	Crohn Disease	BEFREE	19266573, 21887730		★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophageal neoplasm	Pubtator	39287291	Associate	★☆☆☆☆ Found in Text Mining only
Familial medullary thyroid carcinoma	Thyroid cancer	Pubtator	37175943	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	29693188		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	32693062	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	29693188		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Glioma	Glioma	BEFREE	29693188		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	BEFREE	16182110		★☆☆☆☆ Found in Text Mining only
Idiopathic Pulmonary Fibrosis	Idiopathic pulmonary fibrosis	Pubtator	29066090	Associate	★☆☆☆☆ Found in Text Mining only
Intracranial Aneurysm	Intracranial Aneurysm	BEFREE	29997225		★☆☆☆☆ Found in Text Mining only
Intraepithelial Neoplasia	Intraepithelial Neoplasia	BEFREE	23281400		★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	32693062	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	22847784		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	BEFREE	22075569		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	24642040		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	16691626		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	31308489		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	29587866		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	24642040, 29693188, 30482479		★☆☆☆☆ Found in Text Mining only
Malnutrition	Malnutrition	BEFREE	29692779		★☆☆☆☆ Found in Text Mining only
Motor Neuron Disease	Motor Neuron Disease	BEFREE	22835604		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	24642040, 29693188, 31620201		★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	31308489		★☆☆☆☆ Found in Text Mining only
Pancreatic Ductal Adenocarcinoma	Pancreatic adenocarcinoma	BEFREE	31477830		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	22648798, 24817964		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of the head and neck	Carcinoma Of The Head And Neck	BEFREE	22648798		★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	29587866		★☆☆☆☆ Found in Text Mining only
Thyroid Cancer Papillary	Papillary thyroid cancer	Pubtator	37175943	Associate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	24642040		★☆☆☆☆ Found in Text Mining only
Ulcerative Colitis	Ulcerative colitis	BEFREE	20452301		★☆☆☆☆ Found in Text Mining only