RIMS1

Summary

RIMS1 (regulating synaptic membrane exocytosis 1, HGNC:17282) is a protein-coding gene on chromosome 6q13, encoding Regulating synaptic membrane exocytosis protein 1 (Q86UR5). Rab effector involved in exocytosis.

The protein encoded by this gene is a RAS gene superfamily member that regulates synaptic vesicle exocytosis. This gene also plays a role in the regulation of voltage-gated calcium channels during neurotransmitter and insulin release. Mutations have suggested a role cognition and have been identified as the cause of cone-rod dystrophy type 7. Multiple transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 22999 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cone-rod dystrophy 7 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 22
• Clinical variants (ClinVar): 1,347 total — 2 likely-pathogenic
• Phenotypes (HPO): 15
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_014989

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17282
Approved symbol	RIMS1
Name	regulating synaptic membrane exocytosis 1
Location	6q13
Locus type	gene with protein product
Status	Approved
Aliases	RIM, KIAA0340, RIM1
Ensembl gene	ENSG00000079841
Ensembl biotype	protein_coding
OMIM	606629
Entrez	22999

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 17 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000264839, ENST00000370419, ENST00000370420, ENST00000401910, ENST00000414192, ENST00000425662, ENST00000431478, ENST00000453976, ENST00000463023, ENST00000491071, ENST00000517433, ENST00000517827, ENST00000517960, ENST00000518273, ENST00000520567, ENST00000521978, ENST00000522211, ENST00000522291, ENST00000523963, ENST00000524197, ENST00000697193

RefSeq mRNA: 65 — MANE Select: NM_014989 NM_001168407, NM_001168408, NM_001168409, NM_001168410, NM_001168411, NM_001350414, NM_001350415, NM_001350416, NM_001350417, NM_001350418, NM_001350419, NM_001350420, NM_001350421, NM_001350422, NM_001350423, NM_001350424, NM_001350425, NM_001350426, NM_001350427, NM_001350428, NM_001350429, NM_001350430, NM_001350431, NM_001350432, NM_001350433, NM_001350434, NM_001350435, NM_001350436, NM_001350437, NM_001350438, NM_001350439, NM_001350440, NM_001350441, NM_001350442, NM_001350443, NM_001350444, NM_001350445, NM_001350446, NM_001350447, NM_001350448, NM_001350449, NM_001350450, NM_001350452, NM_001350454, NM_001350455, NM_001350456, NM_001350457, NM_001350458, NM_001350459, NM_001350460, NM_001350461, NM_001350462, NM_001350463, NM_001350464, NM_001350465, NM_001350466, NM_001350467, NM_001350468, NM_001350469, NM_001350470, NM_001350471, NM_001350472, NM_001350473, NM_001350474, NM_014989

CCDS: CCDS47449, CCDS55029, CCDS55030, CCDS55031, CCDS55032, CCDS55033

Canonical transcript exons

ENST00000521978 — 34 exons

Exon	Start	End
ENSE00000810433	72274349	72274432
ENSE00001254205	72264975	72265052
ENSE00001335087	72290679	72290861
ENSE00001335090	72265390	72265503
ENSE00002096040	72307258	72307370
ENSE00002105020	72313506	72313672
ENSE00002113467	72333600	72333835
ENSE00002128145	72265960	72266049
ENSE00003478834	72398249	72398350
ENSE00003487467	72248015	72248127
ENSE00003489190	72398955	72399094
ENSE00003491363	72258986	72259111
ENSE00003500012	72284047	72284118
ENSE00003506048	72390598	72390736
ENSE00003517918	72291934	72292046
ENSE00003518997	72250921	72251092
ENSE00003531706	72242314	72242437
ENSE00003539667	72260705	72260767
ENSE00003541586	72237823	72237922
ENSE00003541675	72096949	72097162
ENSE00003547900	71968983	71969063
ENSE00003559730	72252761	72252832
ENSE00003566609	72233773	72233840
ENSE00003582797	72182284	72183149
ENSE00003590848	72250330	72250460
ENSE00003628733	72245815	72245861
ENSE00003648007	72392698	72392810
ENSE00003664433	72258125	72258281
ENSE00003665675	72099975	72099986
ENSE00003671766	72235618	72235728
ENSE00003681925	72179575	72179915
ENSE00003683711	72251215	72251368
ENSE00003924961	72400496	72403145
ENSE00003927658	71886550	71887187

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 95.38.

FANTOM5 (CAGE): breadth broad, TPM avg 3.8788 / max 699.0335, expressed in 458 samples.

FANTOM5 promoters (24 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68511	0.8179	122
68507	0.6228	125
68508	0.5296	155
68509	0.3694	132
68521	0.3266	9
68505	0.1822	72
68510	0.1766	68
68512	0.1368	59
68529	0.1349	42
68506	0.0678	25

Top tissues by expression

276 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cerebellar cortex	UBERON:0002129	95.38	gold quality
cerebellar hemisphere	UBERON:0002245	95.36	gold quality
cerebellum	UBERON:0002037	94.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.73	gold quality
endothelial cell	CL:0000115	93.08	gold quality
middle temporal gyrus	UBERON:0002771	91.63	gold quality
superior frontal gyrus	UBERON:0002661	91.22	gold quality
right frontal lobe	UBERON:0002810	90.68	gold quality
prefrontal cortex	UBERON:0000451	90.50	gold quality
postcentral gyrus	UBERON:0002581	90.29	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.96	gold quality
entorhinal cortex	UBERON:0002728	89.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.33	gold quality
cerebellar vermis	UBERON:0004720	88.66	gold quality
frontal cortex	UBERON:0001870	88.63	gold quality
neocortex	UBERON:0001950	88.14	gold quality
cerebral cortex	UBERON:0000956	87.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.82	gold quality
cingulate cortex	UBERON:0003027	87.68	gold quality
parietal lobe	UBERON:0001872	87.50	gold quality
anterior cingulate cortex	UBERON:0009835	87.33	gold quality
temporal lobe	UBERON:0001871	87.32	gold quality
amygdala	UBERON:0001876	87.17	gold quality
Ammon’s horn	UBERON:0001954	86.56	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.52	gold quality
primary visual cortex	UBERON:0002436	86.09	gold quality
telencephalon	UBERON:0001893	85.21	gold quality
cortical plate	UBERON:0005343	84.71	gold quality
brain	UBERON:0000955	83.84	gold quality
Brodmann (1909) area 46	UBERON:0006483	83.51	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	1938.48
E-HCAD-35	yes	63.97
E-ANND-3	yes	6.37
E-GEOD-99795	no	119.17
E-ENAD-17	no	74.40

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
UNC13A	Activation

miRNA regulators (miRDB)

141 targeting RIMS1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 9)

• Rim1 is a component of the presynaptic active zone and modulator of exocytosis and binds 14-3-3 through its N terminus (PMID:12871946)
• Even though the absence of pathogenic mutations suggests that RIM1 is notinvolved in autosomal recessive retinitis pigmentosa. (PMID:15746564)
• A possible role for RIMS1 in the enhancement of cognitive function at least in this kindred is suggested. (PMID:17237123)
• Rim1 modulates direct G-protein regulation of Ca(v)2.2 channels. (PMID:21331761)
• a novel functional coupling between RIM1 and the L-type Ca(V) channels via the Ca(V)beta auxiliary subunit that contribute to determine insulin secretion. (PMID:21402706)
• Here, we report that, like Rab3A, RIM and Munc13 are present in human sperm and that they play a functional role in acrosomal exocytosis before the acrosomal calcium efflux (PMID:22248876)
• This is the first reported case of bilateral cystoid macular edema in association with the RIM1 mutation. Overall, our findings were more consistent with a phenotype of retinitis pigmentosa. (PMID:27176872)
• The study identified a region on chromosome 6 comprising the genes SMAP1, B3GAT2, and RIMS1 as novel susceptibility locus for pediatric venous thromboembolism. (PMID:28011674)
• Electrophysiological characterization of VDCC currents revealed that the suppressive effect of RIM2alpha on voltage-dependent inactivation (VDI) was stronger than that of RIM1alpha for the CaV2.1 variant containing the region encoded by exons 44 and 47. (PMID:28377503)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rims1a	ENSDARG00000074680
mus_musculus	Rims1	ENSMUSG00000041670
rattus_norvegicus	Rims1	ENSRNOG00000011000
drosophila_melanogaster	Rim	FBGN0053547
caenorhabditis_elegans		WBGENE00006750

Paralogs (4): RIMS4 (ENSG00000101098), RIMS3 (ENSG00000117016), RIMS2 (ENSG00000176406), NANOGNB (ENSG00000205857)

Protein

Protein identifiers

Regulating synaptic membrane exocytosis protein 1 — Q86UR5 (reviewed: Q86UR5)

Alternative names: Rab-3-interacting molecule 1, Rab-3-interacting protein 2

All UniProt accessions (6): Q86UR5, A0A0C4DFV1, A0A8V8TKU9, E5RGM0, H0YBE7, H0YBU6

UniProt curated annotations — full annotation on UniProt →

Function. Rab effector involved in exocytosis. 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. Plays a role in dendrite formation by melanocytes.

Subunit / interactions. Binds RAB3A, RAB3B and RAB3D that have been activated by GTP-binding. Interacts with RAB3C, RAB10, RAB26 and RAB37. Binds UNC13A. Interacts with TSPOAP1 and RIMBP2. Interacts with PPFIA3 and PPFIA4. Interacts with ERC1. Binds SNAP25, SYT1 and CACNA1B. Interaction with SYT1 is enhanced by calcium ions. Interaction with SNAP25 is weaker in the presence of calcium ions.

Subcellular location. Cell membrane. Synapse. Presynaptic cell membrane.

Tissue specificity. Expressed in melanocytes. Detected in brain and retina.

Post-translational modifications. Phosphorylated by BRSK1.

Miscellaneous. May be due to intron retention.

Isoforms (13)

UniProt ID	Names	Canonical?
Q86UR5-1	1, RIM1 alpha	yes
Q86UR5-2	2, RIM short form
Q86UR5-3	3, RIM long form, Rab3 interacting protein variant 2
Q86UR5-4	4, Rab3 interacting protein variant 1
Q86UR5-5	5, Rab3 interacting protein variant 3
Q86UR5-6	6, Rab3 interacting protein variant 4
Q86UR5-7	7, Rab3 interacting protein variant 5
Q86UR5-8	8, Rab3 interacting protein variant 6
Q86UR5-9	9
Q86UR5-10	10
Q86UR5-11	11
Q86UR5-12	12
Q86UR5-13	13

RefSeq proteins (65): NP_001161879, NP_001161880, NP_001161881, NP_001161882, NP_001161883, NP_001337343, NP_001337344, NP_001337345, NP_001337346, NP_001337347, NP_001337348, NP_001337349, NP_001337350, NP_001337351, NP_001337352, NP_001337353, NP_001337354, NP_001337355, NP_001337356, NP_001337357, NP_001337358, NP_001337359, NP_001337360, NP_001337361, NP_001337362, NP_001337363, NP_001337364, NP_001337365, NP_001337366, NP_001337367, NP_001337368, NP_001337369, NP_001337370, NP_001337371, NP_001337372, NP_001337373, NP_001337374, NP_001337375, NP_001337376, NP_001337377, NP_001337378, NP_001337379, NP_001337381, NP_001337383, NP_001337384, NP_001337385, NP_001337386, NP_001337387, NP_001337388, NP_001337389, NP_001337390, NP_001337391, NP_001337392, NP_001337393, NP_001337394, NP_001337395, NP_001337396, NP_001337397, NP_001337398, NP_001337399, NP_001337400, NP_001337401, NP_001337402, NP_001337403, NP_055804* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR001478	PDZ	Domain
IPR010911	Rab_BD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017455	Znf_FYVE-rel	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR039032	Rim-like	Family
IPR054386	RIM_Znf	Domain

Pfam: PF00168, PF00595, PF22601

UniProt features (100 total): modified residue 21, compositionally biased region 19, splice variant 18, region of interest 9, binding site 8, strand 7, sequence conflict 6, domain 4, helix 3, mutagenesis site 2, chain 1, zinc finger region 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2CSS	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86UR5-F1	51.47	0.16

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 116; 119; 132; 135; 140; 143; 162; 165

Post-translational modifications (21): 500, 578, 728, 731, 881, 977, 1031, 1252, 1254, 1256, 1308, 1310, 1311, 1339, 1340, 1342, 1416, 1677, 1680, 1683 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
796–797	abolishes interaction with syt1 and cacna1b.
1591–1592	abolishes interaction with syt1 and cacna1b.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-181429	Serotonin Neurotransmitter Release Cycle
R-HSA-181430	Norepinephrine Neurotransmitter Release Cycle
R-HSA-210500	Glutamate Neurotransmitter Release Cycle
R-HSA-212676	Dopamine Neurotransmitter Release Cycle
R-HSA-264642	Acetylcholine Neurotransmitter Release Cycle
R-HSA-888590	GABA synthesis, release, reuptake and degradation

MSigDB gene sets: 299 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_SINGLE_FERTILIZATION, RRAGTTGT_UNKNOWN, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_MEMBRANE_FUSION, GOBP_GROWTH, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (21): intracellular protein transport (GO:0006886), visual perception (GO:0007601), positive regulation of gene expression (GO:0010628), synaptic vesicle exocytosis (GO:0016079), obsolete synaptic vesicle docking (GO:0016081), synaptic vesicle priming (GO:0016082), calcium-ion regulated exocytosis (GO:0017156), cell differentiation (GO:0030154), regulated exocytosis (GO:0045055), secretion (GO:0046903), regulation of neurotransmitter secretion (GO:0046928), acrosomal vesicle exocytosis (GO:0060478), membrane fusion (GO:0061025), protein-containing complex assembly (GO:0065003), positive regulation of inhibitory postsynaptic potential (GO:0097151), positive regulation of dendrite extension (GO:1903861), regulation of synaptic vesicle exocytosis (GO:2000300), positive regulation of excitatory postsynaptic potential (GO:2000463), neurotransmitter transport (GO:0006836), exocytosis (GO:0006887), maintenance of presynaptic active zone structure (GO:0048790)

GO Molecular Function (7): RNA binding (GO:0003723), zinc ion binding (GO:0008270), GTPase regulator activity (GO:0030695), small GTPase binding (GO:0031267), structural constituent of presynaptic active zone (GO:0098882), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): cytosol (GO:0005829), plasma membrane (GO:0005886), presynaptic membrane (GO:0042734), presynaptic active zone (GO:0048786), presynaptic active zone cytoplasmic component (GO:0098831), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Neurotransmitter release cycle	6

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
presynapse	3
neurotransmitter secretion	2
regulated exocytosis	2
synaptic vesicle exocytosis	2
transport	2
presynaptic active zone	2
intracellular protein localization	1
protein transport	1
intracellular transport	1
sensory perception of light stimulus	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
establishment of localization in cell	1
vesicle-mediated transport in synapse	1
synaptic vesicle cycle	1
signal release from synapse	1
protein-containing complex assembly	1
exocytic process	1
cellular developmental process	1
exocytosis	1
modulation of chemical synaptic transmission	1
regulation of neurotransmitter transport	1
regulation of secretion by cell	1
acrosome reaction	1
calcium-ion regulated exocytosis	1
membrane organization	1
cellular component assembly	1
protein-containing complex organization	1
positive regulation of nervous system process	1
inhibitory postsynaptic potential	1
modulation of inhibitory postsynaptic potential	1
positive regulation of cell growth	1
positive regulation of developmental growth	1
dendrite extension	1
regulation of dendrite extension	1
regulation of neurotransmitter secretion	1
regulation of regulated secretory pathway	1
positive regulation of signal transduction	1

Protein interactions and networks

STRING

1900 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIMS1	UNC13B	O14795	987
RIMS1	RAB3A	P20336	970
RIMS1	UNC13A	Q9UPW8	960
RIMS1	RIMBP2	O15034	955
RIMS1	ERC1	Q8IUD2	942
RIMS1	ERC2	O15083	886
RIMS1	TSPOAP1	O95153	877
RIMS1	RAPGEF4	Q8WZA2	835
RIMS1	SYN1	P17600	783
RIMS1	PITPNM3	Q9BZ71	777
RIMS1	UNC119	Q13432	732
RIMS1	DLG4	P78352	732
RIMS1	SNAP25	P13795	717
RIMS1	STXBP1	P61764	714
RIMS1	GUCY2D	Q02846	713

IntAct

49 interactions, top by confidence:

A	B	Type	Score
E	RIMS1	psi-mi:“MI:0915”(physical association)	0.590
RIMS1	FYN	psi-mi:“MI:0915”(physical association)	0.560
RIMS1	FXR1	psi-mi:“MI:0915”(physical association)	0.500
RIMS1	SRPK2	psi-mi:“MI:0915”(physical association)	0.500
RIMS1	MARK3	psi-mi:“MI:0915”(physical association)	0.500
RIMS1	RALY	psi-mi:“MI:0915”(physical association)	0.500
GABBR2	RIMS1	psi-mi:“MI:0915”(physical association)	0.500
MARK3	RIMS1	psi-mi:“MI:0915”(physical association)	0.500
SRPK2	RIMS1	psi-mi:“MI:0915”(physical association)	0.500
ABCC4	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF16	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
ASIC3	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
ATP2B4	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
CYSLTR2	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKZ	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
DOCK4	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
FRMPD4	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
FZD7	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
TAMALIN	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
E6	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
ORF putative E6	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNA5	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
KIR3DL3	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
RIMS1	MAP2K2	psi-mi:“MI:0407”(direct interaction)	0.440
PBK	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440
RALBP1	RIMS1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (38): RIMS1 (Co-fractionation), RIMS1 (Synthetic Lethality), RIMS1 (Affinity Capture-MS), RIMS1 (Affinity Capture-MS), RIMS1 (Affinity Capture-MS), RIMS1 (Affinity Capture-MS), RIMS1 (Affinity Capture-MS), RIMS1 (Affinity Capture-MS), RIMS1 (Affinity Capture-MS), RIMS1 (Affinity Capture-RNA), RIMS1 (Affinity Capture-MS), RIMS1 (Affinity Capture-Western), RIMS1 (Affinity Capture-Western), RIMS1 (Two-hybrid), RIMS1 (Reconstituted Complex)

ESM2 similar proteins: A0A0R4IZ84, A0A1L8H8C0, A0A1L8HFX9, A2RUV4, F1LP90, F5HSE3, O43310, O60237, O75167, O88453, P41110, P61406, Q12830, Q1LVF3, Q2HJG4, Q2PFD7, Q3TLH4, Q5RAK6, Q5ZMS6, Q66HC1, Q6A0A2, Q6NRP6, Q6NZL0, Q6P1U3, Q6PKG0, Q75N33, Q7TN02, Q7TPM1, Q7YZA2, Q7Z6E9, Q80TN7, Q80XI3, Q86UR5, Q86US8, Q8IVL0, Q8IVL1, Q8K0V4, Q8N4C8, Q90YL3, Q90YY5

Diamond homologs: A0A075F932, A0FGR8, A0FGR9, A4IJ05, A6QP06, O00443, O00445, O00750, O08625, O08835, O35681, P04409, P05128, P05129, P10829, P21521, P21579, P21707, P24505, P24506, P24507, P29101, P34693, P40748, P40749, P41823, P46096, P46097, P47191, P47708, P47709, P47861, P48018, P50232, P59926, P63318, P63319, P70169, P70610, P70611

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
CAMK2A	up-regulates	RIMS1	phosphorylation
RIMS1	“up-regulates activity”	CACNA1D	binding
RIMS1	“up-regulates activity”	RAB3A	relocalization
RIMS1	“up-regulates activity”	RAB3C	relocalization
RIMS1	“up-regulates activity”	UNC13B	relocalization
RIMBP3	“down-regulates activity”	RIMS1	binding
RIMBP2	“down-regulates activity”	RIMS1	binding
RIMBP3C	“down-regulates activity”	RIMS1	binding
TSPOAP1	“down-regulates activity”	RIMS1	binding
RIMBP3B	“down-regulates activity”	RIMS1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
intracellular signal transduction	8	7.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1347 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	796
Likely benign	411
Benign	80

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2430091	NM_014989.7(RIMS1):c.1679-20550G>A	Likely pathogenic
828152	NM_014989.7(RIMS1):c.2770+2T>C	Likely pathogenic

SpliceAI

8124 predictions. Top by Δscore:

Variant	Effect	Δscore
6:71887156:G:GT	donor_gain	1.0000
6:71887183:CTCAA:C	donor_gain	1.0000
6:71887184:TCAA:T	donor_gain	1.0000
6:71887185:CAA:C	donor_gain	1.0000
6:71887185:CAAG:C	donor_loss	1.0000
6:71887186:AA:A	donor_gain	1.0000
6:71887186:AAGTA:A	donor_loss	1.0000
6:71887187:AGTAA:A	donor_loss	1.0000
6:71887188:G:GG	donor_gain	1.0000
6:71887188:GTAAG:G	donor_loss	1.0000
6:71887189:T:G	donor_loss	1.0000
6:71969417:GGTGC:G	donor_gain	1.0000
6:72096942:T:TA	acceptor_gain	1.0000
6:72096945:CTA:C	acceptor_loss	1.0000
6:72096946:TAG:T	acceptor_loss	1.0000
6:72096947:A:AG	acceptor_gain	1.0000
6:72096947:AG:A	acceptor_gain	1.0000
6:72096948:G:GA	acceptor_loss	1.0000
6:72096948:G:GG	acceptor_gain	1.0000
6:72096948:GG:G	acceptor_gain	1.0000
6:72096948:GGA:G	acceptor_gain	1.0000
6:72096948:GGAGA:G	acceptor_gain	1.0000
6:72097158:ACAAC:A	donor_gain	1.0000
6:72097159:CAAC:C	donor_gain	1.0000
6:72097160:AAC:A	donor_gain	1.0000
6:72097160:AACGT:A	donor_loss	1.0000
6:72097161:AC:A	donor_gain	1.0000
6:72097161:ACGTG:A	donor_loss	1.0000
6:72097162:CG:C	donor_loss	1.0000
6:72097163:G:GG	donor_gain	1.0000

AlphaMissense

11003 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:71887106:T:C	L28P	1.000
6:71887118:A:T	E32V	1.000
6:71887122:G:C	R33S	1.000
6:71887122:G:T	R33S	1.000
6:71887130:T:A	I36N	1.000
6:71887130:T:G	I36S	1.000
6:71887135:G:C	A38P	1.000
6:71887148:G:C	R42P	1.000
6:72096979:G:C	K92N	1.000
6:72096979:G:T	K92N	1.000
6:72097049:T:A	C116S	1.000
6:72097049:T:C	C116R	1.000
6:72097050:G:A	C116Y	1.000
6:72097050:G:C	C116S	1.000
6:72097050:G:T	C116F	1.000
6:72097051:T:G	C116W	1.000
6:72097058:T:A	C119S	1.000
6:72097058:T:C	C119R	1.000
6:72097059:G:A	C119Y	1.000
6:72097059:G:C	C119S	1.000
6:72097059:G:T	C119F	1.000
6:72097060:T:G	C119W	1.000
6:72097073:T:C	F124L	1.000
6:72097074:T:C	F124S	1.000
6:72097074:T:G	F124C	1.000
6:72097075:T:A	F124L	1.000
6:72097075:T:G	F124L	1.000
6:72097085:T:A	C128S	1.000
6:72097085:T:C	C128R	1.000
6:72097086:G:A	C128Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000006535 (6:72397368 A>G), RS1000010470 (6:71966707 G>A), RS1000014006 (6:72327477 A>G,T), RS1000017634 (6:72283893 C>G,T), RS1000019870 (6:72014982 A>G), RS1000021605 (6:72144813 C>G), RS1000022205 (6:72370538 A>G), RS1000027655 (6:71896864 T>A), RS1000033581 (6:72102919 A>G,T), RS1000034511 (6:71920993 T>A), RS1000042566 (6:72282925 T>A,C), RS1000048400 (6:72054130 A>C,G), RS1000061955 (6:72162089 T>C), RS1000062504 (6:72145953 G>A), RS1000069246 (6:72014715 A>G)

Disease associations

OMIM: gene MIM:606629 | disease phenotypes: MIM:268000, MIM:603649, MIM:204000, MIM:258870

GenCC curated gene-disease

Disease	Classification	Inheritance
cone-rod dystrophy 7	Strong	Autosomal dominant
autism	Strong	Autosomal dominant
cone-rod dystrophy	Supportive	Autosomal dominant

Mondo (9): inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa (MONDO:0019200), cone-rod dystrophy 7 (MONDO:0011355), Leber congenital amaurosis (MONDO:0018998), long QT syndrome (MONDO:0002442), autism spectrum disorder (MONDO:0005258), ornithine aminotransferase deficiency (MONDO:0009796), cone-rod dystrophy (MONDO:0015993), autism (MONDO:0005260)

Orphanet (6): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), Cone rod dystrophy (Orphanet:1872), Leber congenital amaurosis (Orphanet:65), Gyrate atrophy of choroid and retina (Orphanet:414), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

15 total (16 of 15 shown, HPO-id order):

HPO	Term
HP:0000505	Visual impairment
HP:0000529	Progressive visual loss
HP:0000543	Optic disc pallor
HP:0000551	Color vision defect
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0001105	Retinal atrophy
HP:0007641	Dyschromatopsia
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007843	Attenuation of retinal blood vessels
HP:0012508	Metamorphopsia
HP:0030466	Abnormal full-field electroretinogram
HP:0000556	Retinal dystrophy

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST000579_48	Cognitive performance	4.000000e-06
GCST002156_4	Response to mTOR inhibitor (rapamycin)	8.000000e-06
GCST002263_8	Acute urticaria and angioedema (non-steroidal anti-inflammatory drug-induced)	5.000000e-06
GCST002539_64	Schizophrenia	3.000000e-08
GCST004521_155	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004747_11	Lung cancer in never smokers	9.000000e-06
GCST004748_123	Lung cancer	5.000000e-07
GCST004750_65	Squamous cell lung carcinoma	6.000000e-07
GCST005790_70	Rosacea symptom severity	6.000000e-06
GCST006803_61	Schizophrenia	4.000000e-10
GCST007201_289	Schizophrenia	1.000000e-07
GCST007201_62	Schizophrenia	1.000000e-07
GCST007576_239	Chronotype	5.000000e-11
GCST008103_47	Bipolar disorder	2.000000e-07
GCST009153_4	Adverse response to chemotherapy (amenorrhea) in breast cancer	5.000000e-07
GCST009325_40	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	2.000000e-10
GCST009600_82	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	3.000000e-09
GCST010002_326	Refractive error	3.000000e-205
GCST010244_73	Triglyceride levels	2.000000e-09
GCST011102_8	Bipolar disorder	2.000000e-08
GCST012318_3	Total cholesterol levels x SSRI levels (escitalopram or citalopram) interaction in schizophrenia or bipolar disorder	8.000000e-06
GCST012319_16	LDL levels x SSRI levels (escitalopram or citalopram) interaction in schizophrenia or bipolar disorder	8.000000e-06

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0005417	response to mTOR inhibitor
EFO:0005533	response to non-steroidal anti-inflammatory
EFO:0009180	rosacea severity measurement
EFO:0008328	chronotype measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D015799	Gyrate Atrophy	C11.270.468; C11.941.160.578; C16.320.290.468
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C566350	Cone-Rod Dystrophy 7 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs502046	RIMS1		0.00	0

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, increases expression	5
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, increases mutagenesis	3
bisphenol A	decreases expression, increases methylation	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
sodium arsenite	affects methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Arsenic Trioxide	decreases expression	1
Dexamethasone	increases expression	1
Endosulfan	increases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Thimerosal	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Triclosan	increases expression	1
Asbestos, Crocidolite	decreases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

552 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism