RIN1

protein-coding

Ras and Rab interactor 1, the group of VPS9 domain containing

Gene summary

Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in intracellular signal transduction. Predicted to act upstream of or within associative learning; memory; and negative regulation of synaptic plasticity. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_004292.3

Inheritance

ClinVar variants

U:155B:15

Top phenotype

RIN1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr11:66,330,241-66,336,840

External References & Databases

Ensembl (ENSG00000174791)

Transcript & Mutation Effects

hg38 • Region Span ~6.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial nonmedullary thyroid carcinomaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0017896

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RIN1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 158

not providedTotal: 7

RIN1-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004292.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar	2 clinvar	5
missense			154 clinvar	8 clinvar	2 clinvar	164
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	155	11	4	170

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004292.3	RefSeq	NP_004283.2	10	MANE Select
ENST00000311320.9	Ensembl	ENSP00000310406.4	10	MANE Select
NM_001363559.2	RefSeq	NP_001350488.1	10	Standard
NM_001363560.2	RefSeq	NP_001350489.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ras signaling pathway - Homo sapiens (human)
Ras Signaling
EGF-EGFR Signaling Pathway
Regulation of Ras family activation
Vesicle-mediated transport

Biological Process

endocytosis
signal transduction
memory
associative learning
negative regulation of synaptic plasticity

Molecular Function

GTPase activator activity
protein binding
Rab guanyl-nucleotide exchange factor activity

Cellular Component

cytoplasm
cytosol
cytoskeleton
plasma membrane
dendrite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000311320
Coding exons: 10
Length: 6599
Individuals with no LoFs: 125711
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125739
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.553	410	443	0.926	0.0000279	4808
Missense (PolyPhen)		154	176.06	0.8747		2032
Synonymous	-1.26	223	200	1.11	0.0000119	1777
Loss of Function	1.85	14	23.7	0.591	0.00000128	275

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00018	0.00017	rare
South Asian	0.000033	0.000033	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ras effector protein, which may serve as an inhibitory modulator of neuronal plasticity in aversive memory formation. Can affect Ras signaling at different levels. First, by competing with RAF1 protein for binding to activated Ras. Second, by enhancing signaling from ABL1 and ABL2, which regulate cytoskeletal remodeling. Third, by activating RAB5A, possibly by functioning as a guanine nucleotide exchange factor (GEF) for RAB5A, by exchanging bound GDP for free GTP, and facilitating Ras-activated receptor endocytosis. {ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9208849}.;

Recessive Scores

pRec: 0.141

Intolerance Scores

LoFtool: 0.734
RVIS EVS: 0.27
RVIS percentile EVS: 70.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.909

Gene Damage Prediction

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