RIMS1

regulating synaptic membrane exocytosis 1, the group of PDZ domain containing|Regulating synaptic membrane exocytosis family

Basic information

Region (hg38): 6:71886549-72403150

Previous symbols: [ "RAB3IP2", "CORD7" ]

Links

ENSG00000079841 ∙ NCBI:22999 ∙ OMIM:606629 ∙ HGNC:17282 ∙ Uniprot:Q86UR5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cone-rod dystrophy 7 (Limited), mode of inheritance: AD
• autism spectrum disorder (Limited), mode of inheritance: AD
• cone-rod dystrophy (Supportive), mode of inheritance: AD
• cone-rod dystrophy 7 (Disputed Evidence), mode of inheritance: AD
• cone-rod dystrophy 7 (Limited), mode of inheritance: AD
• cone-rod dystrophy 7 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cone-rod dystrophy 7	AD	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	Ophthalmologic	9634506; 12659814

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RIMS1 gene.

• not provided (956 variants)
• Cone-rod dystrophy 7 (143 variants)
• Inborn genetic diseases (43 variants)
• not specified (18 variants)
• Cone-Rod Dystrophy, Dominant (12 variants)
• Retinal dystrophy (12 variants)
• Retinitis pigmentosa (2 variants)
• Ornithine aminotransferase deficiency (1 variants)
• Leber congenital amaurosis (1 variants)
• Autism spectrum disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RIMS1 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			9	201	21	231
missense			496	11	5	512
nonsense			8			8
start loss			1			1
frameshift			1			1
inframe indel			10			10
splice donor/acceptor (+/-2bp)		1	5			6
splice region			24	27	5	56
non coding		1	47	108	47	203
Total	0	2	577	320	73

Highest pathogenic variant AF is 0.0000197

Variants in RIMS1

This is a list of pathogenic ClinVar variants found in the RIMS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-71886722-C-T		Cone-rod dystrophy 7	Benign (Jan 12, 2018)
6-71886775-C-G		Cone-rod dystrophy 7	Uncertain significance (Jan 13, 2018)
6-71886840-A-AAAG		Cone-Rod Dystrophy, Dominant	Likely benign (Jun 14, 2016)
6-71886843-G-A		Cone-rod dystrophy 7	Uncertain significance (Jan 12, 2018)
6-71886884-T-C		Cone-rod dystrophy 7	Benign (Jan 13, 2018)
6-71886897-G-A		Cone-rod dystrophy 7	Uncertain significance (Jan 13, 2018)
6-71886903-C-T		Cone-rod dystrophy 7	Uncertain significance (Jan 13, 2018)
6-71887011-G-T		Cone-rod dystrophy 7	Uncertain significance (Jan 13, 2018)
6-71887033-G-T			Uncertain significance (Mar 11, 2022)
6-71887036-G-A			Uncertain significance (Jan 19, 2024)
6-71887036-G-C			Likely benign (Jan 19, 2024)
6-71887036-G-T			Uncertain significance (Aug 23, 2022)
6-71887042-C-A			Uncertain significance (Dec 02, 2023)
6-71887049-G-T		not specified	Uncertain significance (Jan 18, 2023)
6-71887051-C-T		Cone-rod dystrophy 7	Conflicting classifications of pathogenicity (Jan 12, 2024)
6-71887052-C-G		Cone-rod dystrophy 7	Uncertain significance (Sep 06, 2022)
6-71887055-G-A			Uncertain significance (Aug 11, 2021)
6-71887055-GC-AA			Uncertain significance (Jul 07, 2023)
6-71887056-C-A			Likely benign (Sep 01, 2022)
6-71887062-C-G		Cone-rod dystrophy 7	Benign/Likely benign (Jul 12, 2023)
6-71887064-C-T			Uncertain significance (Oct 19, 2022)
6-71887068-G-A			Likely benign (Aug 07, 2020)
6-71887072-C-T			Uncertain significance (Oct 24, 2022)
6-71887075-C-A			Uncertain significance (Sep 27, 2022)
6-71887077-C-A			Likely benign (Oct 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RIMS1	protein_coding	protein_coding	ENST00000521978	34	516440

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.990	0.00980	124571	1	70	124642	0.000285

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.01	767	940	0.816	0.0000511	10851
Missense in Polyphen		300	426.98	0.70261		4990
Synonymous	0.293	337	344	0.980	0.0000184	3327
Loss of Function	7.38	19	97.7	0.195	0.00000620	1063

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000252	0.000252
Ashkenazi Jewish	0.00	0.00
East Asian	0.000280	0.000278
Finnish	0.000789	0.000789
European (Non-Finnish)	0.000321	0.000319
Middle Eastern	0.000280	0.000278
South Asian	0.000267	0.000229
Other	0.000166	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Rab effector involved in exocytosis (By similarity). May act as scaffold protein that regulates neurotransmitter release at the active zone. Essential for maintaining normal probability of neurotransmitter release and for regulating release during short- term synaptic plasticity (By similarity). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000250|UniProtKB:Q99NE5, ECO:0000269|PubMed:23999003}.
• Disease: DISEASE: Cone-rod dystrophy 7 (CORD7) [MIM:603649]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:12659814}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: Synaptic vesicle cycle - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);Synaptic Vesicle Pathway;Effects of Botulinum toxin;Neuronal System;Glutamate Neurotransmitter Release Cycle;Dopamine Neurotransmitter Release Cycle;Acetylcholine Neurotransmitter Release Cycle;GABA synthesis, release, reuptake and degradation;Neurotransmitter release cycle;Transmission across Chemical Synapses;Serotonin Neurotransmitter Release Cycle;Norepinephrine Neurotransmitter Release Cycle (Consensus)

Recessive Scores

• pRec: 0.151

Intolerance Scores

• loftool: 0.819
• rvis_EVS: -1.54
• rvis_percentile_EVS: 3.32

Haploinsufficiency Scores

• pHI: 0.521
• hipred: Y
• hipred_score: 0.659
• ghis: 0.600

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.741

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rims1
• Phenotype: normal 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); 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;visual perception;positive regulation of gene expression;synaptic vesicle exocytosis;calcium ion regulated exocytosis;regulation of membrane potential;regulated exocytosis;secretion;regulation of neurotransmitter secretion;regulation of synaptic plasticity;calcium ion-regulated exocytosis of neurotransmitter;regulation of catalytic activity;positive regulation of synaptic transmission;response to stimulus;membrane fusion;protein-containing complex assembly;positive regulation of inhibitory postsynaptic potential;positive regulation of dendrite extension;regulation of synaptic vesicle exocytosis;positive regulation of excitatory postsynaptic potential
• Cellular component: cytosol;plasma membrane;cell junction;presynaptic membrane;synapse;presynaptic active zone;cytoskeleton of presynaptic active zone;presynaptic active zone cytoplasmic component
• Molecular function: RNA binding;protein binding;Rab GTPase binding;GTPase regulator activity;ion channel binding;metal ion binding