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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Macrocephaly, alopecia, cutis laxa, and scoliosis	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 (6 variants)
• RIN2 syndrome (1 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	131	6	139
missense			204	7	7	218
nonsense	2		2			4
start loss						0
frameshift	4	2	3			9
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2				2
splice region			2	10	1	13
non coding			16	72	29	117
Total	6	4	228	210	42

Highest pathogenic variant AF is 0.00000666

Variants in RIN2

This is a list of pathogenic ClinVar variants found in the RIN2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-19886282-G-A			Benign (Jun 19, 2018)
20-19886398-C-T			Benign (Jun 18, 2018)
20-19886489-C-T			Likely benign (Aug 12, 2018)
20-19886606-CTTCTTCTTT-C			Likely benign (Sep 03, 2019)
20-19886606-CTTCTTCTTTT-C			Likely benign (Aug 12, 2018)
20-19886608-TC-T			Benign (Sep 19, 2019)
20-19886612-C-T			Benign (Aug 08, 2019)
20-19886612-CT-C			Benign (Aug 16, 2019)
20-19886612-CTTTTTTTT-C			Likely benign (Aug 06, 2019)
20-19886612-C-CT			Benign (Aug 06, 2019)
20-19886612-C-CTT			Likely benign (Sep 23, 2019)
20-19886667-G-A		RIN2-related disorder	Likely benign (Aug 05, 2022)
20-19886676-G-T			Uncertain significance (Sep 29, 2021)
20-19886680-C-G			Uncertain significance (Nov 28, 2022)
20-19886681-AT-A			Uncertain significance (Sep 04, 2022)
20-19886698-CT-C			Benign (Jan 31, 2024)
20-19886705-C-T			Likely benign (Oct 17, 2022)
20-19886724-A-T			Uncertain significance (Oct 17, 2022)
20-19886725-G-C			Uncertain significance (Oct 20, 2021)
20-19886730-A-G			Uncertain significance (Apr 28, 2022)
20-19886731-G-T		Inborn genetic diseases	Uncertain significance (May 15, 2024)
20-19886740-C-T		not specified • RIN2-related disorder	Likely benign (Feb 01, 2024)
20-19886741-G-C			Likely benign (Aug 27, 2022)
20-19886749-T-C			Uncertain significance (Mar 12, 2022)
20-19886751-T-C			Uncertain significance (Dec 09, 2023)

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

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