RAPGEF4 (Rap guanine nucleotide exchange factor 4)

Gene

• Entrez ID: 11069
• Gene name: Rap guanine nucleotide exchange factor 4
• Gene symbol: RAPGEF4
• Synonyms (NCBI Gene): CAMP-GEFII, CGEF2, EPAC, EPAC 2, EPAC2, Nbla00496
• Chromosome: 2
• Chromosome location: 2q31.1

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018141	hsa-miR-335-5p	Microarray	18185580
MIRT027613	hsa-miR-98-5p	Microarray	19088304
MIRT029706	hsa-miR-26b-5p	Microarray	19088304
MIRT156411	hsa-miR-106b-5p	HITS-CLIP	22473208
MIRT156404	hsa-miR-20a-5p	HITS-CLIP	22473208
MIRT156411	hsa-miR-106b-5p	HITS-CLIP	22473208
MIRT156401	hsa-miR-17-5p	HITS-CLIP	22473208
MIRT156417	hsa-miR-20b-5p	HITS-CLIP	22473208
MIRT156406	hsa-miR-93-5p	HITS-CLIP	22473208
MIRT156424	hsa-miR-519d-3p	HITS-CLIP	22473208
MIRT156402	hsa-miR-19a-3p	HITS-CLIP	22473208
MIRT156403	hsa-miR-19b-3p	HITS-CLIP	22473208
MIRT156404	hsa-miR-20a-5p	HITS-CLIP	22473208
MIRT1290845	hsa-miR-106a	CLIP-seq
MIRT1290846	hsa-miR-106b	CLIP-seq
MIRT1290847	hsa-miR-130a	CLIP-seq
MIRT1290848	hsa-miR-130b	CLIP-seq
MIRT1290849	hsa-miR-17	CLIP-seq
MIRT1290850	hsa-miR-19a	CLIP-seq
MIRT1290851	hsa-miR-19b	CLIP-seq
MIRT1290852	hsa-miR-20a	CLIP-seq
MIRT1290853	hsa-miR-20b	CLIP-seq
MIRT1290854	hsa-miR-301a	CLIP-seq
MIRT1290855	hsa-miR-301b	CLIP-seq
MIRT1290856	hsa-miR-3666	CLIP-seq
MIRT1290857	hsa-miR-4295	CLIP-seq
MIRT1290858	hsa-miR-454	CLIP-seq
MIRT1290859	hsa-miR-488	CLIP-seq
MIRT1290860	hsa-miR-519a	CLIP-seq
MIRT1290861	hsa-miR-519b-3p	CLIP-seq
MIRT1290862	hsa-miR-519c-3p	CLIP-seq
MIRT1290863	hsa-miR-519d	CLIP-seq
MIRT1290864	hsa-miR-93	CLIP-seq
MIRT2086496	hsa-miR-1265	CLIP-seq
MIRT2086497	hsa-miR-1266	CLIP-seq
MIRT2086498	hsa-miR-1273e	CLIP-seq
MIRT2086499	hsa-miR-129-5p	CLIP-seq
MIRT2086500	hsa-miR-3664-3p	CLIP-seq
MIRT2086501	hsa-miR-4518	CLIP-seq
MIRT2086502	hsa-miR-4764-5p	CLIP-seq
MIRT2086496	hsa-miR-1265	CLIP-seq
MIRT2086497	hsa-miR-1266	CLIP-seq
MIRT2086498	hsa-miR-1273e	CLIP-seq
MIRT2086499	hsa-miR-129-5p	CLIP-seq
MIRT2086500	hsa-miR-3664-3p	CLIP-seq
MIRT2086501	hsa-miR-4518	CLIP-seq
MIRT2086502	hsa-miR-4764-5p	CLIP-seq
MIRT2607976	hsa-miR-3681	CLIP-seq
MIRT2607977	hsa-miR-3924	CLIP-seq
MIRT2607978	hsa-miR-410	CLIP-seq
MIRT2607979	hsa-miR-4460	CLIP-seq
MIRT2607980	hsa-miR-4727-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0002250	Process	Adaptive immune response	IEA
GO:0002250	Process	Adaptive immune response	TAS
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	EXP	15334074, 16076873
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IBA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IEA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	ISS
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	TAS	9856955
GO:0005515	Function	Protein binding	IPI	11438518, 24722188, 25416956, 32296183, 32814053
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	TAS
GO:0006887	Process	Exocytosis	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS	9856955
GO:0007188	Process	Adenylate cyclase-modulating G protein-coupled receptor signaling pathway	IEA
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IEA
GO:0007264	Process	Small GTPase-mediated signal transduction	IEA
GO:0007265	Process	Ras protein signal transduction	IBA
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	TAS	10777494
GO:0017156	Process	Calcium-ion regulated exocytosis	IEA
GO:0017157	Process	Regulation of exocytosis	IEA
GO:0030073	Process	Insulin secretion	IEA
GO:0030552	Function	CAMP binding	IEA
GO:0030552	Function	CAMP binding	ISS
GO:0030552	Function	CAMP binding	TAS
GO:0030674	Function	Protein-macromolecule adaptor activity	IEA
GO:0031267	Function	Small GTPase binding	IEA
GO:0031267	Function	Small GTPase binding	ISS
GO:0032024	Process	Positive regulation of insulin secretion	IEA
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0046879	Process	Hormone secretion	IEA
GO:0050796	Process	Regulation of insulin secretion	IEA
GO:0050796	Process	Regulation of insulin secretion	TAS
GO:0098686	Component	Hippocampal mossy fiber to CA3 synapse	IEA
GO:0098693	Process	Regulation of synaptic vesicle cycle	IEA

Other IDs

• MIM: 606058
• HGNC: 16626
• e!Ensembl: ENSG00000091428

Protein

• UniProt ID: Q8WZA2
• Protein name: Rap guanine nucleotide exchange factor 4 (Exchange factor directly activated by cAMP 2) (Exchange protein directly activated by cAMP 2) (EPAC 2) (cAMP-regulated guanine nucleotide exchange factor II) (cAMP-GEFII)
• Protein function: Guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and RAP2A small GTPases that is activated by binding cAMP. Seems not to activate RAB3A. Involved in cAMP-dependent, PKA-independent exocytosis through interaction with RIMS2 (By similarit
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00027	cNMP_binding	61 → 150	Cyclic nucleotide-binding domain	Domain
  PF00610	DEP	220 → 289	Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)	Domain
  PF00027	cNMP_binding	375 → 459	Cyclic nucleotide-binding domain	Domain
  PF00618	RasGEF_N	499 → 605	RasGEF N-terminal motif	Domain
  PF00617	RasGEF	775 → 952	RasGEF domain	Family

• Tissue specificity: TISSUE SPECIFICITY: Predominantly expressed in brain and adrenal gland. Isoform 2 is expressed in liver. Isoform 1 is expressed in liver at very low levels.
• Sequence:

  MVAAHAAHSSSSAEWIACLDKRPLERSSEDVDIIFTRLKEVKAFEKFHPNLLHQICLCGY
  YENLEKGITLFRQGDIGTNWYAVLAGSLDVKVSETSSHQDAVTICTLGIGTAFGESILDN
  TPRHATIVTRESSELLRIEQKDFKALWEKYRQYMAGLLAPPYGVMETGSNNDRIPDKENT
  PLIEPHVPLRPANTITKVPSEKILRAGKILRNAILSRAPHMIRDRKYHLKTYRQCCVGTE
  LVDWMMQQTPCVHSRTQAVGMWQVLLEDGVLNHVDQEHHFQDKYLFYRFLDDEHEDAPLP
  TEEEKKECDEELQDTMLLLSQMGPDAHMRMILRKPPGQRTVDDLEIIYEELLHIKALSHL
  STTVKRELAGVLIFESHAKGGTVLFNQGEEGTSWYIILKGSVNVVIYGKGVVCTLHEGDD
  FGKLALVNDAPRAASIVLREDNCHFLRVDKEDFNRILRDVEANTVRLKEHDQDVLVLEKV
  PAGNRASNQGNSQPQQKYTVMSGTPEKILEHFLETIRLEATLNEATDSVLNDFIMMHCVF
  MPNTQLCPALVAHYHAQPSQGTEQEKMDYALNNKRRVIRLVLQWAAMYGDLLQEDDVSMA
  FLEEFYVSVSDDARMIAALKEQLPELEKIVKQISEDAKAPQKKHKVLLQQFNTGDERAQK
  RQPIRGSDEVLFKVYCMDHTYTTIRVPVATSVKEVISAVADKLGSGEGLIIVKMSSGGEK
  VVLKPNDVSVFTTLTINGRLFACPREQFDSLTPLPEQEGPTVGTVGTFELMSSKDLAYQM
  TIYDWELFNCVHELELIYHTFGRHNFKKTTANLDLFLRRFNEIQFWVVTEICLCSQLSKR
  VQLLKKFIKIAAHCKEYKNLNSFFAIVMGLSNVAVSRLALTWEKLPSKFKKFYAEFESLM
  DPSRNHRAYRLTVAKLEPPLIPFMPLLIKDMTFTHEGNKTFIDNLVNFEKMRMIANTART
  VRYYRSQPFNPDAAQANKNHQDVRSYVRQLNVIDNQRTLSQMSHRLEPRRP

• Sequence length: 1011

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
AUTISTIC DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOYAMOYA DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CANCER	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anxiety	Anxiety Disorder	BEFREE	27598965		★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety Disorder	BEFREE	27598965		★☆☆☆☆ Found in Text Mining only
Astrocytoma	Astrocytoma	BEFREE	24714982		★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	31059774		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	BEFREE	14593429, 19734897, 22745599		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic Disorder	Autism	Pubtator	24204716	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bladder Neoplasm	Bladder Neoplasm	BEFREE	29111327		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	26474971	Associate	★☆☆☆☆ Found in Text Mining only
Bronchiolitis	Bronchiolitis	BEFREE	30185593		★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	29111327		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	31316160, 31726720		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular disease	Pubtator	31316160, 31726720	Associate	★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	19734897, 27598965		★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	31726720		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	31726720		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	31726720	Associate	★☆☆☆☆ Found in Text Mining only
Disturbance in mood	Mood Disorder	BEFREE	27598965		★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	34337010	Associate	★☆☆☆☆ Found in Text Mining only
Follicular thyroid carcinoma	Follicular Thyroid Carcinoma	BEFREE	29882482		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	31186720		★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	27598965		★☆☆☆☆ Found in Text Mining only
Left Ventricular Hypertrophy	Left Ventricular Hypertrophy	BEFREE	17557924		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	28232663	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	29111327		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	28283242, 29375750		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	28851815		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	35834616	Associate	★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	19734897, 27598965		★☆☆☆☆ Found in Text Mining only
Metastatic melanoma	Metastatic Melanoma	BEFREE	28851815		★☆☆☆☆ Found in Text Mining only
Mood Disorders	Mood Disorder	BEFREE	27598965		★☆☆☆☆ Found in Text Mining only
Moyamoya Disease	Moyamoya Disease	GWASCAT_DG	29273593		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Moyamoya disease 1	Moyamoya disease	GWASCAT_DG	29273593		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	27709364		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	27867203		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	37800580	Associate	★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	32800727	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	GWASCAT_DG	31374203		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Steatohepatitis	Fatty Liver	BEFREE	31551444		★☆☆☆☆ Found in Text Mining only
Thyroid cancer, follicular	Thyroid cancer	BEFREE	29882482		★☆☆☆☆ Found in Text Mining only
Thyroid carcinoma	Thyroid Carcinoma	BEFREE	25372777		★☆☆☆☆ Found in Text Mining only
Thyroid Neoplasm	Thyroid Neoplasm	BEFREE	25372777		★☆☆☆☆ Found in Text Mining only
Torsades de Pointes	Torsades de Pointes	BEFREE	27649969		★☆☆☆☆ Found in Text Mining only
Vascular Remodeling	Vascular remodeling	Pubtator	31316160	Associate	★☆☆☆☆ Found in Text Mining only