RIMS3

Summary

RIMS3 (regulating synaptic membrane exocytosis 3, HGNC:21292) is a protein-coding gene on chromosome 1p34.2, encoding Regulating synaptic membrane exocytosis protein 3 (Q9UJD0). Regulates synaptic membrane exocytosis.

Predicted to enable transmembrane transporter binding activity. Predicted to be a structural constituent of presynaptic active zone. Predicted to be involved in several processes, including regulated exocytosis; regulation of synapse organization; and regulation of synaptic vesicle exocytosis. Predicted to be located in presynaptic active zone. Predicted to be active in several cellular components, including postsynaptic cytosol; presynaptic active zone cytoplasmic component; and presynaptic membrane.

Source: NCBI Gene 9783 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 60 total
• MANE Select transcript: NM_014747

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21292
Approved symbol	RIMS3
Name	regulating synaptic membrane exocytosis 3
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	RIM3, NIM3
Ensembl gene	ENSG00000117016
Ensembl biotype	protein_coding
OMIM	611600
Entrez	9783

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000372683, ENST00000372684, ENST00000858245, ENST00000858246, ENST00000913649, ENST00000913650, ENST00000913651

RefSeq mRNA: 1 — MANE Select: NM_014747 NM_014747

CCDS: CCDS30687

Canonical transcript exons

ENST00000372684 — 8 exons

Exon	Start	End
ENSE00000768606	40635916	40636057
ENSE00000768607	40633069	40633181
ENSE00000768608	40629271	40629372
ENSE00000768609	40628810	40628949
ENSE00001415774	40647668	40647842
ENSE00001458392	40620680	40626729
ENSE00001458398	40641709	40641956
ENSE00001458399	40665394	40665682

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 99.65.

FANTOM5 (CAGE): breadth broad, TPM avg 5.5797 / max 195.9858, expressed in 844 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11932	5.5436	842
11931	0.0220	8
11930	0.0141	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.65	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.54	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.41	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.71	gold quality
superior frontal gyrus	UBERON:0002661	98.70	gold quality
orbitofrontal cortex	UBERON:0004167	98.25	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.17	gold quality
frontal pole	UBERON:0002795	98.01	gold quality
postcentral gyrus	UBERON:0002581	97.93	gold quality
parietal lobe	UBERON:0001872	97.91	gold quality
primary visual cortex	UBERON:0002436	97.89	gold quality
occipital lobe	UBERON:0002021	97.62	gold quality
entorhinal cortex	UBERON:0002728	96.61	gold quality
frontal cortex	UBERON:0001870	96.54	gold quality
right frontal lobe	UBERON:0002810	96.37	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.05	gold quality
cerebellar vermis	UBERON:0004720	95.99	gold quality
prefrontal cortex	UBERON:0000451	95.75	gold quality
neocortex	UBERON:0001950	95.58	gold quality
endothelial cell	CL:0000115	95.53	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.31	gold quality
adult organism	UBERON:0007023	94.87	gold quality
cingulate cortex	UBERON:0003027	93.91	gold quality
anterior cingulate cortex	UBERON:0009835	93.87	gold quality
paraflocculus	UBERON:0005351	93.79	gold quality
cerebral cortex	UBERON:0000956	93.68	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	92.13	gold quality
cerebellum	UBERON:0002037	92.11	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.88	gold quality
cerebellar cortex	UBERON:0002129	91.76	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

296 targeting RIMS3, 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-6758-5P	100.00	66.21	1470
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910

Literature-anchored findings (GeneRIF, showing 2)

• Western blot analysis shows increased piccolo protein expression in the amygdala in schizophrenia. (PMID:18490030)
• We identified four novel CNVs in three different genes (one duplication in USH2A gene, two duplications in CEP290 gene, and one duplication in RIMS2 gene) in total four families, at a detection rate of 8% (4/50). (PMID:28118666)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rims3	ENSDARG00000062305
mus_musculus	Rims3	ENSMUSG00000032890
rattus_norvegicus	Rims3	ENSRNOG00000011171
drosophila_melanogaster	Rim	FBGN0053547
caenorhabditis_elegans		WBGENE00006750

Paralogs (4): RIMS1 (ENSG00000079841), RIMS4 (ENSG00000101098), RIMS2 (ENSG00000176406), NANOGNB (ENSG00000205857)

Protein

Protein identifiers

Regulating synaptic membrane exocytosis protein 3 — Q9UJD0 (reviewed: Q9UJD0)

Alternative names: RIM3 gamma, Rab-3-interacting molecule 3

All UniProt accessions (1): Q9UJD0

UniProt curated annotations — full annotation on UniProt →

Function. Regulates synaptic membrane exocytosis.

Subunit / interactions. Binds PPFIA3. Does not bind RAB3.

Subcellular location. Synapse.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UJD0-1	1	yes
Q9UJD0-2	2

RefSeq proteins (1): NP_055562* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR039032	Rim-like	Family

Pfam: PF00168

UniProt features (9 total): modified residue 2, splice variant 2, chain 1, domain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJD0-F1	71.86	0.42

Functional residue map

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

Post-translational modifications (2): 295, 298

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 244 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, AAGCAAT_MIR137, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, CACCAGC_MIR138, GOBP_CELL_CELL_SIGNALING, GOBP_MEMBRANE_DOCKING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, MODULE_66, GOBP_EXOCYTOSIS, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_VESICLE_DOCKING_INVOLVED_IN_EXOCYTOSIS

GO Biological Process (8): obsolete synaptic vesicle docking (GO:0016081), synaptic vesicle priming (GO:0016082), calcium-ion regulated exocytosis (GO:0017156), regulation of membrane potential (GO:0042391), regulation of synaptic vesicle exocytosis (GO:2000300), neurotransmitter transport (GO:0006836), exocytosis (GO:0006887), maintenance of presynaptic active zone structure (GO:0048790)

GO Molecular Function (4): small GTPase binding (GO:0031267), transmembrane transporter binding (GO:0044325), structural constituent of presynaptic active zone (GO:0098882), protein binding (GO:0005515)

GO Cellular Component (5): presynaptic membrane (GO:0042734), presynaptic active zone (GO:0048786), presynaptic active zone cytoplasmic component (GO:0098831), membrane (GO:0016020), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synaptic vesicle exocytosis	2
presynaptic active zone	2
presynapse	2
cellular anatomical structure	2
protein-containing complex assembly	1
exocytic process	1
regulated exocytosis	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
regulation of neurotransmitter secretion	1
regulation of regulated secretory pathway	1
transport	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
maintenance of synapse structure	1
presynaptic active zone organization	1
GTPase binding	1
protein binding	1
maintenance of presynaptic active zone structure	1
structural constituent of synapse	1
binding	1
synaptic membrane	1
cell cortex region	1
cell junction	1

Protein interactions and networks

STRING

1342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIMS3	IL1RAPL1	Q9NZN1	586
RIMS3	NLGN3	Q9NZ94	453
RIMS3	METAP1D	Q6UB28	436
RIMS3	ODAD4	Q96NG3	418
RIMS3	ERBIN	Q96RT1	418
RIMS3	AGFG1	P52594	416
RIMS3	DISP1	Q96F81	411
RIMS3	FEZ1	Q99689	407
RIMS3	NIM1K	Q8IY84	399
RIMS3	EPHA6	Q9UF33	388
RIMS3	MYCBP2	O75592	385
RIMS3	CIBAR2	Q6ZTR7	375
RIMS3	PPFIA3	O75145	373
RIMS3	ERC1	Q8IUD2	370
RIMS3	UNC13B	O14795	369

IntAct

45 interactions, top by confidence:

A	B	Type	Score
RIMS3	YWHAG	psi-mi:“MI:0915”(physical association)	0.740
MEOX2	RIMS3	psi-mi:“MI:0915”(physical association)	0.560
PICK1	RIMS3	psi-mi:“MI:0915”(physical association)	0.560
	RIMS3	psi-mi:“MI:0915”(physical association)	0.560
RIMS3	COMT	psi-mi:“MI:0915”(physical association)	0.560
RIMS3	HLA-A	psi-mi:“MI:0915”(physical association)	0.560
RIMS3	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
RIMS3	VIM	psi-mi:“MI:0915”(physical association)	0.560
RIMS3	SETDB1	psi-mi:“MI:0915”(physical association)	0.560
RIMS3	KAT5	psi-mi:“MI:0915”(physical association)	0.560
LMO3	RIMS3	psi-mi:“MI:0915”(physical association)	0.560
RIMS3	ZDHHC17	psi-mi:“MI:0915”(physical association)	0.400
RIMS3	E7	psi-mi:“MI:0915”(physical association)	0.370
RIMS3	BANP	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (12): RIMS3 (Two-hybrid), RIMS3 (Two-hybrid), RIMS3 (Two-hybrid), BCL2L2-PABPN1 (Two-hybrid), RIMS3 (Two-hybrid), RIMS1 (Affinity Capture-MS), RIMS3 (Affinity Capture-MS), RIMS2 (Affinity Capture-MS), POTEF (Affinity Capture-MS), RIMS3 (Two-hybrid), RIMS3 (Two-hybrid), BANP (Two-hybrid)

ESM2 similar proteins: A6QP06, B2RRD7, D2I3C6, E7FDW2, F1LP90, O43896, O54880, P00519, P00520, P00521, P11434, P42684, P47708, P47709, P55201, Q06846, Q12873, Q2T9V9, Q4JIM5, Q4V7A6, Q6DTM3, Q6ZRS2, Q80U57, Q80UP3, Q80VW5, Q86UR5, Q8BMD7, Q8BRB7, Q8N4C8, Q8N568, Q8WUB8, Q91VY5, Q99N50, Q99NE5, Q9D8M7, Q9EQ32, Q9EQZ7, Q9GLM4, Q9H4G0, Q9HBL0

Diamond homologs: A0A0G2K344, A0FGR8, A6QP06, G5EDY0, O00443, O00445, O00750, O02697, O35681, O43581, O70167, O70173, O75747, P21521, P24505, P24506, P24507, P29101, P32871, P40748, P41823, P41885, P42336, P42337, P42338, P42339, P42347, P42348, P46097, P47708, P47709, P48736, P50520, P54673, P54674, P54675, P54676, P60191, P63318, P63319

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
RIMS3	“up-regulates activity”	CACNA1D	binding
RIMS3	“up-regulates activity”	RAB3A	relocalization
RIMS3	“up-regulates activity”	RAB3C	relocalization
RIMS3	“up-regulates activity”	UNC13B	relocalization
RIMBP3	“down-regulates activity”	RIMS3	binding
RIMBP2	“down-regulates activity”	RIMS3	binding
RIMBP3C	“down-regulates activity”	RIMS3	binding
TSPOAP1	“down-regulates activity”	RIMS3	binding
RIMBP3B	“down-regulates activity”	RIMS3	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1460 predictions. Top by Δscore:

Variant	Effect	Δscore
1:40626506:T:TA	donor_gain	1.0000
1:40626514:T:TA	donor_gain	1.0000
1:40626545:T:A	donor_gain	1.0000
1:40626725:ATCAC:A	acceptor_gain	1.0000
1:40626726:TCAC:T	acceptor_gain	1.0000
1:40626726:TCACC:T	acceptor_loss	1.0000
1:40626727:CAC:C	acceptor_gain	1.0000
1:40626727:CACC:C	acceptor_gain	1.0000
1:40626727:CACCT:C	acceptor_loss	1.0000
1:40626728:AC:A	acceptor_gain	1.0000
1:40626729:CC:C	acceptor_gain	1.0000
1:40626730:C:A	acceptor_loss	1.0000
1:40626730:C:CC	acceptor_gain	1.0000
1:40626731:T:A	acceptor_loss	1.0000
1:40626734:C:CT	acceptor_gain	1.0000
1:40626735:A:T	acceptor_gain	1.0000
1:40628805:CCCA:C	donor_loss	1.0000
1:40628807:CACC:C	donor_loss	1.0000
1:40628808:ACCT:A	donor_loss	1.0000
1:40628809:C:CT	donor_loss	1.0000
1:40628945:GGTGG:G	acceptor_gain	1.0000
1:40628946:GTGG:G	acceptor_gain	1.0000
1:40628947:TGG:T	acceptor_gain	1.0000
1:40628948:GG:G	acceptor_gain	1.0000
1:40628949:GC:G	acceptor_loss	1.0000
1:40628950:C:CC	acceptor_gain	1.0000
1:40629265:CCTCA:C	donor_loss	1.0000
1:40629266:CTCA:C	donor_loss	1.0000
1:40629267:TCA:T	donor_loss	1.0000
1:40629268:CACC:C	donor_loss	1.0000

AlphaMissense

1996 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:40626680:C:A	G255V	1.000
1:40626681:C:A	G255C	1.000
1:40626681:C:G	G255R	1.000
1:40626720:A:G	W242R	1.000
1:40626720:A:T	W242R	1.000
1:40626722:A:T	V241D	1.000
1:40628814:A:G	L237P	1.000
1:40628936:C:A	K196N	1.000
1:40628936:C:G	K196N	1.000
1:40628938:T:C	K196E	1.000
1:40626614:A:G	F277S	0.999
1:40626617:A:G	L276P	0.999
1:40626617:A:T	L276H	0.999
1:40626623:T:G	Y274S	0.999
1:40626624:A:C	Y274D	0.999
1:40626674:G:T	A257D	0.999
1:40626680:C:T	G255D	0.999
1:40626685:G:C	F253L	0.999
1:40626685:G:T	F253L	0.999
1:40626687:A:G	F253L	0.999
1:40626718:C:A	W242C	0.999
1:40626718:C:G	W242C	0.999
1:40628814:A:C	L237R	0.999
1:40628841:A:G	F228S	0.999
1:40628900:C:A	K208N	0.999
1:40628900:C:G	K208N	0.999
1:40628928:A:G	L199P	0.999
1:40628932:A:C	Y198D	0.999
1:40628934:A:T	V197D	0.999
1:40629313:C:G	A178P	0.999

dbSNP variants (sampled 300 via entrez): RS1000000440 (1:40625031 G>A), RS1000072262 (1:40621336 A>C), RS1000099129 (1:40669173 A>C,G), RS1000152269 (1:40649921 G>A), RS1000165796 (1:40627590 C>A,T), RS1000215626 (1:40692598 A>G,T), RS1000263860 (1:40649655 A>C), RS1000275866 (1:40693406 G>A), RS1000308994 (1:40681857 G>A), RS1000331924 (1:40656526 G>A), RS1000362595 (1:40683018 C>A), RS1000391599 (1:40675871 T>C), RS1000435469 (1:40640322 G>T), RS1000474174 (1:40689053 T>C,G), RS1000483951 (1:40648425 A>G)

Disease associations

OMIM: gene MIM:611600 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

53 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	6
Benzo(a)pyrene	affects methylation, decreases expression	3
bisphenol A	increases expression	2
entinostat	increases expression, affects cotreatment	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Hydrogen Peroxide	affects expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tretinoin	decreases expression	2
Tunicamycin	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
methylselenic acid	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
vanadyl sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1

Clinical trials (associated diseases)

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