RIN2

Ras and Rab interactor 2, the group of VPS9 domain containing

Basic information

Region (hg38): 20:19757606-20002457

Links

ENSG00000132669

∙ NCBI:54453 ∙ OMIM:610222 ∙ HGNC:18750 ∙ Uniprot:Q8WYP3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

RIN2 syndrome (Strong), mode of inheritance: AR
RIN2 syndrome (Strong), mode of inheritance: AR
RIN2 syndrome (Strong), mode of inheritance: AR
RIN2 syndrome (Supportive), mode of inheritance: AR
RIN2 syndrome (Definitive), mode of inheritance: AR
RIN2 syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Macrocephaly, alopecia, cutis laxa, and scoliosis (MACS syndrome)	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic	19631308; 20424861; 21431621; 23963297;24449201

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RIN2 gene.

not_provided (490 variants)
Inborn_genetic_diseases (146 variants)
not_specified (45 variants)
RIN2-related_disorder (39 variants)
RIN2_syndrome (25 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RIN2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018993.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	147 clinvar	4 clinvar	154
missense			266 clinvar	19 clinvar	6 clinvar	291
nonsense	2 clinvar	1 clinvar	2 clinvar			5
start loss						0
frameshift	8 clinvar	3 clinvar	6 clinvar			17
splice donor/acceptor (+/-2bp)		3 clinvar				3
Total	10	7	277	166	10

Highest pathogenic variant AF is 0.00001968522

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RIN2	protein_coding	protein_coding	ENST00000255006	12	115937

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000814	0.999	124622	0	18	124640	0.0000722

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.724	490	537	0.912	0.0000309	6122
Missense in Polyphen		145	196.94	0.73628		2313
Synonymous	0.365	223	230	0.969	0.0000147	1864
Loss of Function	3.65	12	35.4	0.339	0.00000179	442

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000942	0.0000941
Ashkenazi Jewish	0.0000994	0.0000994
East Asian	0.0000557	0.0000556
Finnish	0.0000968	0.0000928
European (Non-Finnish)	0.0000644	0.0000619
Middle Eastern	0.0000557	0.0000556
South Asian	0.000136	0.000131
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

Function: 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 GDP for free GTP. {ECO:0000269|PubMed:11733506}.;
Pathway: Vesicle-mediated transport;Membrane Trafficking;Rab regulation of trafficking;Posttranslational regulation of adherens junction stability and dissassembly;RAB GEFs exchange GTP for GDP on RABs;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met) (Consensus)

Recessive Scores

pRec: 0.133

Intolerance Scores

loftool: 0.602
rvis_EVS: 0.52
rvis_percentile_EVS: 80.4

Haploinsufficiency Scores

pHI: 0.196
hipred: Y
hipred_score: 0.756
ghis: 0.493

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.584

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Rin2
Phenotype

Gene ontology

Biological process: endocytosis;small GTPase mediated signal transduction;positive regulation of GTPase activity
Cellular component: cellular_component;cytosol
Molecular function: GTPase activator activity;Rab guanyl-nucleotide exchange factor activity;GTPase regulator activity