RIMS2

regulating synaptic membrane exocytosis 2, the group of Regulating synaptic membrane exocytosis family|PDZ domain containing

Basic information

Region (hg38): 8:103500610-104254430

Previous symbols: [ "RAB3IP3" ]

Links

ENSG00000176406 ∙ NCBI:9699 ∙ OMIM:606630 ∙ HGNC:17283 ∙ Uniprot:Q9UQ26 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cone-rod synaptic disorder, congenital nonprogressive (Strong), mode of inheritance: AR
• cone-rod synaptic disorder syndrome, congenital nonprogressive (Limited), mode of inheritance: AR
• cone-rod synaptic disorder syndrome, congenital nonprogressive (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cone-rod synaptic disorder syndrome, congenital nonprogressive	AR	Endocrine	Among other features, metabolic dysfunction (including hyperglycemia and insulin resistance) has been described and suggested as an age-related manifestation, and awareness may allow early identification and management	Endocrine; Neurologic; Ophthalmologic	32470375

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RIMS2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RIMS2 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				7	4	11
missense			75	2	6	83
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				2		2
non coding				3		3
Total	0	1	75	12	10

Variants in RIMS2

This is a list of pathogenic ClinVar variants found in the RIMS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-103500928-C-A			Benign (Dec 31, 2019)
8-103500963-T-C		not specified	Uncertain significance (Jan 06, 2023)
8-103500981-T-C		not specified	Uncertain significance (Dec 19, 2023)
8-103501030-G-T		not specified	Uncertain significance (Mar 29, 2022)
8-103697199-A-T		not specified	Uncertain significance (Apr 01, 2024)
8-103697254-C-G		not specified	Uncertain significance (Mar 28, 2024)
8-103766247-G-T		not specified	Uncertain significance (Feb 07, 2023)
8-103766294-A-G		not specified	Uncertain significance (Dec 17, 2023)
8-103766311-A-G		not specified	Uncertain significance (Mar 01, 2024)
8-103766333-A-T		not specified	Uncertain significance (Jun 24, 2022)
8-103766374-A-C		not specified	Uncertain significance (Dec 02, 2022)
8-103766377-A-C		not specified	Uncertain significance (Aug 02, 2021)
8-103766399-C-T			Benign (Dec 31, 2019)
8-103766428-T-C		not specified	Uncertain significance (Jul 05, 2023)
8-103766454-A-G			Likely benign (Dec 31, 2019)
8-103766492-G-T		not specified	Uncertain significance (Nov 10, 2022)
8-103766524-A-G			Likely benign (Dec 31, 2019)
8-103885293-C-T			Likely benign (Oct 19, 2018)
8-103885311-T-C		not specified	Uncertain significance (Jun 09, 2022)
8-103885314-G-T			Likely benign (Dec 28, 2018)
8-103885341-G-A		not specified	Uncertain significance (Dec 18, 2023)
8-103885391-C-T			Benign (Dec 31, 2019)
8-103885407-C-T		not specified	Uncertain significance (May 01, 2023)
8-103885459-A-T			Benign (Dec 31, 2019)
8-103885578-G-A		not specified	Uncertain significance (Apr 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RIMS2	protein_coding	protein_coding	ENST00000406091	24	755347

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000117	124763	0	32	124795	0.000128

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.776	697	757	0.921	0.0000422	8727
Missense in Polyphen		316	396.17	0.79763		4526
Synonymous	-0.559	269	258	1.04	0.0000131	2626
Loss of Function	7.38	10	82.2	0.122	0.00000520	888

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000742	0.000740
Ashkenazi Jewish	0.000300	0.000298
East Asian	0.0000567	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.0000806	0.0000794
Middle Eastern	0.0000567	0.0000556
South Asian	0.000200	0.000196
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Rab effector involved in exocytosis. May act as scaffold protein. Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:23999003}.
• Pathway: Insulin secretion - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.783
• rvis_EVS: -0.59
• rvis_percentile_EVS: 18.28

Haploinsufficiency Scores

• pHI: 0.853
• hipred: Y
• hipred_score: 0.750
• ghis: 0.574

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.592

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rims2
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: intracellular protein transport;positive regulation of gene expression;calcium ion regulated exocytosis;regulation of exocytosis;cAMP-mediated signaling;insulin secretion;regulation of membrane potential;regulation of synaptic plasticity;calcium ion-regulated exocytosis of neurotransmitter;positive regulation of synaptic transmission;spontaneous neurotransmitter secretion;positive regulation of inhibitory postsynaptic potential;positive regulation of dendrite extension;regulation of synaptic vesicle exocytosis;positive regulation of excitatory postsynaptic potential
• Cellular component: cell junction;presynaptic membrane;synapse;presynaptic active zone;cytoskeleton of presynaptic active zone;extracellular exosome;presynaptic active zone cytoplasmic component
• Molecular function: protein binding;Rab GTPase binding;ion channel binding;metal ion binding