RIN2 (Ras and Rab interactor 2)

Gene

• Entrez ID: 54453
• Gene name: Ras and Rab interactor 2
• Gene symbol: RIN2
• Synonyms (NCBI Gene): MACS, RASSF4
• Chromosome: 20
• Chromosome location: 20p11.23
• Summary: The RAB5 protein is a small GTPase involved in membrane trafficking in the early endocytic pathway. The protein encoded by this gene binds the GTP-bound form of the RAB5 protein preferentially over the GDP-bound form, and functions as a guanine nucleotide

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs183028833	C>A,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Intron variant, coding sequence variant, upstream transcript variant, missense variant, 5 prime UTR variant, genic upstream transcript variant
rs183141566	A>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Genic downstream transcript variant, missense variant, coding sequence variant
rs199954296	C>A,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Missense variant, coding sequence variant, synonymous variant
rs200780805	C>G	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant
rs201486809	C>A,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Missense variant, coding sequence variant
rs201964534	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Genic downstream transcript variant, missense variant, coding sequence variant
rs587776915	GC>-	Pathogenic	Coding sequence variant, frameshift variant, genic downstream transcript variant
rs759390822	C>-,CC	Pathogenic	Coding sequence variant, frameshift variant
rs1568718508	->C	Likely-pathogenic	Coding sequence variant, genic downstream transcript variant, frameshift variant
rs1600939486	->AC	Likely-pathogenic	Coding sequence variant, 5 prime UTR variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT016643	hsa-miR-429	Reporter assay	20005803
MIRT020353	hsa-miR-200a-3p	Reporter assay	20005803
MIRT021076	hsa-miR-200c-3p	Reporter assay	20005803
MIRT021656	hsa-miR-141-3p	Reporter assay	20005803
MIRT024130	hsa-miR-200b-3p	Reporter assay	20005803
MIRT1307290	hsa-miR-3910	CLIP-seq
MIRT1307291	hsa-miR-4668-3p	CLIP-seq
MIRT1307292	hsa-miR-4717-3p	CLIP-seq
MIRT1307293	hsa-miR-4778-5p	CLIP-seq
MIRT1307294	hsa-miR-548an	CLIP-seq
MIRT1307295	hsa-miR-944	CLIP-seq
MIRT1307296	hsa-miR-101	CLIP-seq
MIRT1307297	hsa-miR-144	CLIP-seq
MIRT1307298	hsa-miR-485-3p	CLIP-seq
MIRT1307299	hsa-miR-487a	CLIP-seq
MIRT2091087	hsa-miR-1238	CLIP-seq
MIRT2091088	hsa-miR-607	CLIP-seq
MIRT2432749	hsa-miR-3163	CLIP-seq
MIRT2432750	hsa-miR-4645-3p	CLIP-seq
MIRT2432751	hsa-miR-4772-3p	CLIP-seq
MIRT2432752	hsa-miR-891b	CLIP-seq
MIRT2611874	hsa-miR-1267	CLIP-seq
MIRT2611875	hsa-miR-217	CLIP-seq
MIRT2611876	hsa-miR-3130-3p	CLIP-seq
MIRT2611877	hsa-miR-3133	CLIP-seq
MIRT2611878	hsa-miR-3182	CLIP-seq
MIRT2611879	hsa-miR-4452	CLIP-seq
MIRT2611880	hsa-miR-4511	CLIP-seq
MIRT2611881	hsa-miR-4659a-3p	CLIP-seq
MIRT2611882	hsa-miR-4659b-3p	CLIP-seq
MIRT2611883	hsa-miR-4686	CLIP-seq
MIRT2611884	hsa-miR-4793-3p	CLIP-seq
MIRT2611885	hsa-miR-521	CLIP-seq
MIRT2611886	hsa-miR-544	CLIP-seq
MIRT2611887	hsa-miR-595	CLIP-seq
MIRT2611888	hsa-miR-643	CLIP-seq
MIRT2611889	hsa-miR-653	CLIP-seq
MIRT2611874	hsa-miR-1267	CLIP-seq
MIRT2611875	hsa-miR-217	CLIP-seq
MIRT2611879	hsa-miR-4452	CLIP-seq
MIRT2611883	hsa-miR-4686	CLIP-seq
MIRT2611885	hsa-miR-521	CLIP-seq
MIRT2689775	hsa-miR-579	CLIP-seq
MIRT2611889	hsa-miR-653	CLIP-seq
MIRT2689776	hsa-miR-664	CLIP-seq
MIRT2689777	hsa-miR-548t	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
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	NAS	11733506
GO:0005096	Function	GTPase activator activity	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	TAS
GO:0006897	Process	Endocytosis	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0007264	Process	Small GTPase-mediated signal transduction	NAS	1849280
GO:0010595	Process	Positive regulation of endothelial cell migration	IMP	22825554
GO:0016192	Process	Vesicle-mediated transport	IEA
GO:0030139	Component	Endocytic vesicle	IBA
GO:0030695	Function	GTPase regulator activity	NAS	1849280
GO:0031267	Function	Small GTPase binding	IBA
GO:1904906	Process	Positive regulation of endothelial cell-matrix adhesion via fibronectin	IMP	22825554
GO:2001214	Process	Positive regulation of vasculogenesis	IMP	22825554

Other IDs

• MIM: 610222
• HGNC: 18750
• e!Ensembl: ENSG00000132669

Protein

• UniProt ID: Q8WYP3
• Protein name: Ras and Rab interactor 2 (Ras association domain family 4) (Ras inhibitor JC265) (Ras interaction/interference protein 2)
• Protein function: Ras effector protein. May function as an upstream activator and/or downstream effector for RAB5B in endocytic pathway. May function as a guanine nucleotide exchange (GEF) of RAB5B, required for activating the RAB5 proteins by exchanging bound GD
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02204	VPS9	651 → 753	Vacuolar sorting protein 9 (VPS9) domain	Family
  PF00788	RA	787 → 878	Ras association (RalGDS/AF-6) domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed. Expressed in heart, kidney, lung placenta. Expressed at low level in skeletal muscle, spleen and peripheral blood. {ECO:0000269|PubMed:11733506}.
• Sequence:

  MTAWTMGARGLDKRGSFFKLIDTIASEIGELKQEMVRTDVNLENGLEPAETHSMVRHKDG
  GYSEEEDVKTCARDSGYDSLSNRLSILDRLLHTHPIWLQLSLSEEEAAEVLQAQPPGIFL
  VHKSTKMQKKVLSLRLPCEFGAPLKEFAIKESTYTFSLEGSGISFADLFRLIAFYCISRD
  VLPFTLKLPYAISTAKSEAQLEELAQMGLNFWSSPADSKPPNLPPPHRPLSSDGVCPASL
  RQLCLINGVHSIKTRTPSELECSQTNGALCFINPLFLKVHSQDLSGGLKRPSTRTPNANG
  TERTRSPPPRPPPPAINSLHTSPRLARTETQTSMPETVNHNKHGNVALPGTKPTPIPPPR
  LKKQASFLEAEGGAKTLSGGRPGAGPELELGTAGSPGGAPPEAAPGDCTRAPPPSSESRP
  PCHGGRQRLSDMSISTSSSDSLEFDRSMPLFGYEADTNSSLEDYEGESDQETMAPPIKSK
  KKRSSSFVLPKLVKSQLQKVSGVFSSFMTPEKRMVRRIAELSRDKCTYFGCLVQDYVSFL
  QENKECHVSSTDMLQTIRQFMTQVKNYLSQSSELDPPIESLIPEDQIDVVLEKAMHKCIL
  KPLKGHVEAMLKDFHMADGSWKQLKENLQLVRQRNPQELGVFAPTPDFVDVEKIKVKFMT
  MQKMYSPEKKVMLLLRVCKLIYTVMENNSGRMYGADDFLPVLTYVIAQCDMLELDTEIEY
  MMELLDPSLLHGEGGYYLTSAYGALSLIKNFQEEQAARLLSSETRDTLRQWHKRRTTNRT
  IPSVDDFQNYLRVAFQEVNSGCTGKTLLVRPYITTEDVCQICAEKFKVGDPEEYSLFLFV
  DETWQQLAEDTYPQKIKAELHSRPQPHIFHFVYKRIKNDPYGIIFQNGEEDLTTS

• Sequence length: 895

Pathways

Reactome:

RAB GEFs exchange GTP for GDP on RABs

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
RIN2 syndrome	Pathogenic; Likely pathogenic	rs759390822, rs587776915, rs1568718508, rs1600939486	RCV000125476 RCV000001359 RCV000030606 RCV000721940 RCV000991410	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
BIPOLAR DISORDER	—	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
CEREBRAL ATHEROSCLEROSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign; Likely benign	ClinVar	★★☆☆☆ 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
MENTAL OR BEHAVIOURAL DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RIN2-related disorder	Likely benign; Conflicting classifications of pathogenicity; Uncertain significance; Benign	ClinVar	★★☆☆☆ 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
Acute lymphocytic leukemia	Lymphocytic Leukemia	BEFREE	25884180		★☆☆☆☆ Found in Text Mining only
Adult Acute Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	25884180		★☆☆☆☆ Found in Text Mining only
Allergic sensitization	Allergic Sensitization	BEFREE	30288821		★☆☆☆☆ Found in Text Mining only
Alopecia	Alopecia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm	Aortic Aneurysm	HPO_DG			★☆☆☆☆ Found in Text Mining only
Bardet-Biedl Syndrome	Bardet-Biedl Syndrome	BEFREE	31521835		★☆☆☆☆ Found in Text Mining only
Barrett Esophagus	Barrett esophagus	BEFREE	23243219		★☆☆☆☆ Found in Text Mining only
Barrett Esophagus	Barrett esophagus	Pubtator	23243219	Associate	★☆☆☆☆ 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	30482232		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	23243219	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	29843871		★☆☆☆☆ Found in Text Mining only
Cerebral Palsy	Cerebral palsy	BEFREE	31679451		★☆☆☆☆ Found in Text Mining only
Childhood Acute Lymphoblastic Leukemia	Lymphoblastic Leukemia	BEFREE	25884180		★☆☆☆☆ Found in Text Mining only
Choriocarcinoma	Choriocarcinoma	BEFREE	11200816		★☆☆☆☆ Found in Text Mining only
Congenital exomphalos	Congenital Exomphalos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Connective Tissue Diseases	Connective Tissue Disease	BEFREE	27277385		★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cutis Laxa	Cutis laxa	Pubtator	19631308	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Familial multiple trichoepitheliomata	Multiple Trichoepithelioma	BEFREE	23243219		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	31804699		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	31804699		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Glioma	Glioma	BEFREE	23338840		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Impaired cognition	Impaired Cognition	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	23970349		★☆☆☆☆ Found in Text Mining only
Macrocephaly	Macrocephaly	BEFREE	30769224		★☆☆☆☆ Found in Text Mining only
Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis	Macrocephaly, Alopecia, Cutis Laxa, And Scoliosis	ORPHANET_DG	19631308, 24449201		★☆☆☆☆ Found in Text Mining only
Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis	Macrocephaly, Alopecia, Cutis Laxa, And Scoliosis	BEFREE	24449201, 30769224		★☆☆☆☆ Found in Text Mining only
Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis	Macrocephaly, Alopecia, Cutis Laxa, And Scoliosis	GENOMICS_ENGLAND_DG	27277385		★☆☆☆☆ Found in Text Mining only
Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis	Macrocephaly, Alopecia, Cutis Laxa, And Scoliosis	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Macrocephaly, Alopecia, Cutis Laxa, and Scoliosis	Macrocephaly, Alopecia, Cutis Laxa, And Scoliosis	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	30482232		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	23970349		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	29843871		★☆☆☆☆ Found in Text Mining only
Meningomyelocele	Meningomyelocele	BEFREE	9598313		★☆☆☆☆ Found in Text Mining only
Mental disorders	Mental Disorders	GWASDB_DG	20889312		★☆☆☆☆ Found in Text Mining only
Mental disorders	Mental Disorders	GWASCAT_DG	20889312		★☆☆☆☆ Found in Text Mining only
Metabolic Syndrome X	Metabolic Syndrome	BEFREE	16521160		★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	BEFREE	11027834		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	31547863		★☆☆☆☆ Found in Text Mining only
Neural Tube Defects	Neural Tube Defect	BEFREE	9598313		★☆☆☆☆ Found in Text Mining only
Non-obstructive azoospermia	Non-obstructive azoospermia	BEFREE	29193985		★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	Pubtator	38484114	Associate	★☆☆☆☆ Found in Text Mining only
Premature Menopause	Premature Menopause	HPO_DG			★☆☆☆☆ Found in Text Mining only
Primary hypogonadism	Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychosis	GWASCAT_DG	20889312		★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychosis	GWASDB_DG	20889312		★☆☆☆☆ Found in Text Mining only
RIN2 syndrome	RIN2 Syndrome	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Scoliosis	Scoliosis	Pubtator	19631308	Associate	★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	BEFREE	30769224		★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Severe myopia	Myopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spastic cerebral palsy	Spastic Cerebral Palsy	BEFREE	27465858		★☆☆☆☆ Found in Text Mining only