RASA2 (RAS p21 protein activator 2)

Gene

• Entrez ID: 5922
• Gene name: RAS p21 protein activator 2
• Gene symbol: RASA2
• Synonyms (NCBI Gene): GAP1M
• Chromosome: 3
• Chromosome location: 3q23
• Summary: The protein encoded by this gene is member of the GAP1 family of GTPase-activating proteins. The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018937	hsa-miR-335-5p	Microarray	18185580
MIRT447367	hsa-miR-548l	PAR-CLIP	22100165
MIRT447365	hsa-miR-3973	PAR-CLIP	22100165
MIRT447366	hsa-miR-4635	PAR-CLIP	22100165
MIRT447364	hsa-miR-4470	PAR-CLIP	22100165
MIRT447363	hsa-miR-203a-3p	PAR-CLIP	22100165
MIRT447362	hsa-miR-182-5p	PAR-CLIP	22100165
MIRT736525	hsa-miR-31-3p	Microarray, qRT-PCR	32925730
MIRT447367	hsa-miR-548l	PAR-CLIP	22100165
MIRT447365	hsa-miR-3973	PAR-CLIP	22100165
MIRT447366	hsa-miR-4635	PAR-CLIP	22100165
MIRT447364	hsa-miR-4470	PAR-CLIP	22100165
MIRT447363	hsa-miR-203a-3p	PAR-CLIP	22100165
MIRT447362	hsa-miR-182-5p	PAR-CLIP	22100165
MIRT2086816	hsa-miR-145	CLIP-seq
MIRT2086817	hsa-miR-3180-5p	CLIP-seq
MIRT2086818	hsa-miR-3182	CLIP-seq
MIRT2086819	hsa-miR-4277	CLIP-seq
MIRT2086820	hsa-miR-4539	CLIP-seq
MIRT2086821	hsa-miR-4659a-3p	CLIP-seq
MIRT2086822	hsa-miR-4659b-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005096	Function	GTPase activator activity	IBA
GO:0005096	Function	GTPase activator activity	IEA
GO:0005096	Function	GTPase activator activity	TAS	8812506
GO:0005515	Function	Protein binding	IPI	33961781
GO:0005543	Function	Phospholipid binding	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	TAS
GO:0007165	Process	Signal transduction	TAS	8699317, 8812506
GO:0008270	Function	Zinc ion binding	IEA
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0046580	Process	Negative regulation of Ras protein signal transduction	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	IEA
GO:1902531	Process	Regulation of intracellular signal transduction	IBA

Other IDs

• MIM: 601589
• HGNC: 9872
• e!Ensembl: ENSG00000155903

Protein

• UniProt ID: Q15283
• Protein name: Ras GTPase-activating protein 2 (GTPase-activating protein 1m) (GAP1m)
• Protein function: Inhibitory regulator of the Ras-cyclic AMP pathway. Binds inositol tetrakisphosphate (IP4).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00168	C2	38 → 140	C2 domain	Domain
  PF00168	C2	171 → 291	C2 domain	Domain
  PF00616	RasGAP	377 → 454	GTPase-activator protein for Ras-like GTPase	Family
  PF00616	RasGAP	444 → 550	GTPase-activator protein for Ras-like GTPase	Family
  PF00169	PH	605 → 706	PH domain	Domain
  PF00779	BTK	714 → 743	BTK motif	Motif

• Sequence:

  MAAAAPAAAAASSEAPAASATAEPEAGDQDSREVRVLQSLRGKICEAKNLLPYLGPHKMR
  DCFCTINLDQEEVYRTQVVEKSLSPFFSEEFYFEIPRTFQYLSFYVYDKNVLQRDLRIGK
  VAIKKEDLCNHSGKETWFSLQPVDSNSEVQGKVHLELKLNELITENGTVCQQLVVHIKAC
  HGLPLINGQSCDPYATVSLVGPSRNDQKKTKVKKKTSNPQFNEIFYFEVTRSSSYTRKSQ
  FQVEEEDIEKLEIRIDLWNNGNLVQDVFLGEIKVPVNVLRTDSSHQAWYLLQPRDNGNKS
  SKTDDLGSLRLNICYTEDYVLPSEYYGPLKTLLLKSPDVQPISASAAYILSEICRDKNDA
  VLPLVRLLLHHDKLVPFATAVAELDLKDTQDANTIFRGNSLATRCLDEMMKIVGGHYLKV
  TLKPILDEICDSSKSCEIDPIKLKEGDNVENNKENLRYYVDKLFNTIVKSSMSCPTVMCD
  IFYSLRQMATQRFPNDPHVQYSAVSSFVFLRFFAVAVVSPHTFHLRPHHPDAQTIRTLTL
  ISKTIQTLGSWGSLSKSKSSFKETFMCEFFKMFQEEGYIIAVKKFLDEISSTETKESSGT
  SEPVHLKEGEMYKRAQGRTRIGKKNFKKRWFCLTSRELTYHKQPGSKDAIYTIPVKNILA
  VEKLEESSFNKKNMFQVIHTEKPLYVQANNCVEANEWIDVLCRVSRCNQNRLSFYHPSVY
  LNGNWLCCQETGENTLGCKPCTAGVPADIQIDIDEDRETERIYSLFTLSLLKLQKMEEAC
  GTIAVYQGPQKEPDDYSNFVIEDSVTTFKTIQQIKSIIEKLDEPHEKYRKKRSSSAKYGS
  KENPIVGKAS

• Sequence length: 850

Pathways

KEGG:

MAPK signaling pathway
Ras signaling pathway
Viral carcinogenesis

Reactome:

Regulation of RAS by GAPs

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)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Noonan syndrome 1	Likely pathogenic	rs1169587141	RCV003454375	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASTHMA	—	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
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary cancer-predisposing syndrome	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MELANOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MULTIPLE MYELOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NOONAN SYNDROME	—	ClinGen, Disgenet, GWAS catalog, Orphanet ClinGen, Disgenet, GWAS catalog, Orphanet ClinGen, Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, HIP	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, KNEE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN SEROUS CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RASA2-related disorder	Likely benign; Conflicting classifications of pathogenicity; Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Abnormal dermatoglyphic pattern	Abnormal dermatoglyphic pattern	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brachydactyly	Brachydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	GWASCAT_DG	29059683		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Carcinoma	Breast Carcinoma	BEFREE	29228687		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
CAPILLARY MALFORMATION-ARTERIOVENOUS MALFORMATION (disorder)	Capillary Malformation-Arteriovenous Malformation	BEFREE	23687085, 30026675		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	27039262	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	26925973		★☆☆☆☆ Found in Text Mining only
Cardio-facio-cutaneous syndrome	Cardiofaciocutaneous syndrome	CLINGEN_DG			★☆☆☆☆ Found in Text Mining only
Clinodactyly of the 5th finger	Camptodactyly of fingers	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	21570766		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	30858928		★☆☆☆☆ Found in Text Mining only
Congenital pectus carinatum	Congenital Pectus Carinatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital pectus excavatum	Congenital Pectus Excavatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Costello syndrome (disorder)	Costello syndrome	CLINGEN_DG			★☆☆☆☆ Found in Text Mining only
Creutzfeldt-Jakob Disease, Sporadic	Creutzfeldt-Jakob disease	BEFREE	29216791		★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Exophthalmos	Proptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Fatal Familial Insomnia	Fatal Insomnia	BEFREE	29216791		★☆☆☆☆ Found in Text Mining only
Head and Neck Carcinoma	Head And Neck Carcinoma	BEFREE	26925973		★☆☆☆☆ Found in Text Mining only
Hypogonadotropic hypogonadism	Hypogonadotropic Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Insomnia Fatal Familial	Insomnia	Pubtator	29216791	Associate	★☆☆☆☆ Found in Text Mining only
LEOPARD Syndrome	LEOPARD Syndrome	CLINGEN_DG			★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	14978793		★☆☆☆☆ Found in Text Mining only
liposarcoma	Liposarcoma	BEFREE	26925973		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	40311306	Associate	★☆☆☆☆ Found in Text Mining only
Lymphangioma, Cystic	Cystic hygroma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant Head and Neck Neoplasm	Head and neck cancer	BEFREE	26925973		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	27974415, 29228687		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	28150874		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	26925973		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	26925973, 9877179		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	26502337		★☆☆☆☆ Found in Text Mining only
Medullary carcinoma of thyroid	Megalencephaly, Polymicrogyria, Polydactyly, Hydrocephalus Syndrome	BEFREE	31298226		★☆☆☆☆ Found in Text Mining only
Melanocytic nevus	Melanocytic nevus	HPO_DG			★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	26214590, 26502337, 26993606		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
melanoma	Melanoma	CTD_human_DG	26214590, 26502337		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Melanoma	Pubtator	26502337	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neck webbing	Neck Webbing	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	15492507, 17510315, 27974415, 28150874, 31312020		★☆☆☆☆ Found in Text Mining only
Neurofibromatosis 1	Neurofibromatosis	BEFREE	29670214		★☆☆☆☆ Found in Text Mining only
Noonan Syndrome	Noonan Syndrome	BEFREE	25049390		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Noonan Syndrome	Noonan Syndrome	CLINGEN_DG	25049390		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Noonan Syndrome	Noonan Syndrome	ORPHANET_DG	25049390		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Noonan Syndrome	Noonan syndrome	Pubtator	25049390	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Noonan syndrome	Noonan Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Noonan syndrome-like disorder with loose anagen hair	Noonan-Like Syndrome With Loose Anagen Hair	CLINGEN_DG			★☆☆☆☆ Found in Text Mining only
Noonan-Like Syndrome With Loose Anagen Hair	Noonan-Like Syndrome With Loose Anagen Hair	CLINGEN_DG			★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	29228687		★☆☆☆☆ Found in Text Mining only
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma	Lymphoblastic Leukemia	BEFREE	26549032		★☆☆☆☆ Found in Text Mining only
Prion Diseases	Prion disease	Pubtator	29216791	Associate	★☆☆☆☆ Found in Text Mining only
Prostate cancer, familial	Prostate cancer	BEFREE	9877179		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	26925973, 9877179		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	26925973	Associate	★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Radioulnar Synostosis	Radioulnar Synostosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Scoliosis	Scoliosis	Pubtator	34440387	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sezary Syndrome	Sezary syndrome	Pubtator	27039262	Associate	★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Thyroid cancer medullary	Medullary thyroid cancer	Pubtator	31298226	Associate	★☆☆☆☆ Found in Text Mining only