RIMS4

Summary

RIMS4 (regulating synaptic membrane exocytosis 4, HGNC:16183) is a protein-coding gene on chromosome 20q13.12, encoding Regulating synaptic membrane exocytosis protein 4 (Q9H426). Regulates synaptic membrane exocytosis.

Predicted to enable transmembrane transporter binding activity. Predicted to be involved in regulation of membrane potential; regulation of synapse organization; and regulation of synaptic vesicle exocytosis. Predicted to be located in synaptic membrane. Predicted to be active in glutamatergic synapse.

Source: NCBI Gene 140730 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 17 total — 1 pathogenic
• MANE Select transcript: NM_182970

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16183
Approved symbol	RIMS4
Name	regulating synaptic membrane exocytosis 4
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	dJ781B1.3
Ensembl gene	ENSG00000101098
Ensembl biotype	protein_coding
OMIM	611601
Entrez	140730

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000372851, ENST00000541604

RefSeq mRNA: 2 — MANE Select: NM_182970 NM_001205317, NM_182970

CCDS: CCDS13338, CCDS56191

Canonical transcript exons

ENST00000372851 — 6 exons

Exon	Start	End
ENSE00000662283	44756898	44757037
ENSE00000662284	44757670	44757771
ENSE00000662285	44758072	44758184
ENSE00000662286	44771275	44771413
ENSE00000844884	44751808	44756352
ENSE00001415314	44810175	44810546

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 96.62.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4009 / max 64.1136, expressed in 394 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187363	1.0120	344
187364	0.3889	191

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	96.62	gold quality
right frontal lobe	UBERON:0002810	90.65	gold quality
nucleus accumbens	UBERON:0001882	90.60	gold quality
anterior cingulate cortex	UBERON:0009835	89.95	gold quality
prefrontal cortex	UBERON:0000451	89.53	gold quality
cortical plate	UBERON:0005343	88.85	gold quality
caudate nucleus	UBERON:0001873	87.88	gold quality
frontal cortex	UBERON:0001870	87.72	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.72	gold quality
putamen	UBERON:0001874	87.70	gold quality
neocortex	UBERON:0001950	87.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.31	gold quality
amygdala	UBERON:0001876	86.55	gold quality
cerebral cortex	UBERON:0000956	85.71	gold quality
forebrain	UBERON:0001890	84.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.96	gold quality
brain	UBERON:0000955	83.75	gold quality
epithelial cell of pancreas	CL:0000083	83.28	gold quality
cerebellar hemisphere	UBERON:0002245	83.13	gold quality
cerebellar cortex	UBERON:0002129	83.09	gold quality
Ammon’s horn	UBERON:0001954	82.99	gold quality
pancreatic ductal cell	CL:0002079	82.86	silver quality
cerebellum	UBERON:0002037	82.59	gold quality
temporal lobe	UBERON:0001871	81.93	gold quality
hypothalamus	UBERON:0001898	81.63	gold quality
adenohypophysis	UBERON:0002196	81.08	gold quality
superior frontal gyrus	UBERON:0002661	79.68	gold quality
vena cava	UBERON:0004087	79.64	gold quality
upper arm skin	UBERON:0004263	79.60	gold quality
kidney epithelium	UBERON:0004819	79.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

257 targeting RIMS4, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rims4	ENSDARG00000059523
mus_musculus	Rims4	ENSMUSG00000035226
rattus_norvegicus	Rims4	ENSRNOG00000074704
drosophila_melanogaster	Rim	FBGN0053547
caenorhabditis_elegans		WBGENE00006750

Paralogs (4): RIMS1 (ENSG00000079841), RIMS3 (ENSG00000117016), RIMS2 (ENSG00000176406), NANOGNB (ENSG00000205857)

Protein

Protein identifiers

Regulating synaptic membrane exocytosis protein 4 — Q9H426 (reviewed: Q9H426)

Alternative names: RIM4 gamma, Rab3-interacting molecule 4

All UniProt accessions (1): Q9H426

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?
Q9H426-1	1	yes
Q9H426-2	2

RefSeq proteins (2): NP_001192246, NP_892015* (*=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 (5 total): modified residue 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H426-F1	71.97	0.46

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): 254, 257

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 162 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, RNGTGGGC_UNKNOWN, AAGCAAT_MIR137, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_EXOCYTOSIS, GCAAGGA_MIR502, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, CTAGGAA_MIR384, GOBP_EXOCYTOSIS, ACATTCC_MIR1_MIR206

GO Biological Process (4): neurotransmitter transport (GO:0006836), exocytosis (GO:0006887), regulation of membrane potential (GO:0042391), regulation of synaptic vesicle exocytosis (GO:2000300)

GO Molecular Function (3): small GTPase binding (GO:0031267), transmembrane transporter binding (GO:0044325), protein binding (GO:0005515)

GO Cellular Component (4): presynaptic active zone (GO:0048786), synaptic membrane (GO:0097060), membrane (GO:0016020), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
transport	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
synaptic vesicle exocytosis	1
regulation of neurotransmitter secretion	1
regulation of regulated secretory pathway	1
GTPase binding	1
protein binding	1
binding	1
presynapse	1
synapse	1
plasma membrane region	1
cell junction	1

Protein interactions and networks

STRING

1170 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIMS4	ZNF540	Q8NDQ6	505
RIMS4	PYURF	Q96I23	501
RIMS4	FAM78A	Q5JUQ0	473
RIMS4	WDR93	Q6P2C0	468
RIMS4	ALKAL1	Q6UXT8	447
RIMS4	ZNF154	Q13106	444
RIMS4	PCYOX1	Q9UHG3	442
RIMS4	ZNF671	Q8TAW3	419
RIMS4	ZNF804B	A4D1E1	403
RIMS4	KHDRBS2	Q5VWX1	396
RIMS4	ERC1	Q8IUD2	395
RIMS4	PPP4R3C	Q6ZMV5	394
RIMS4	PCDHAC1	Q9H158	378
RIMS4	RAB3C	Q96E17	374
RIMS4	MYO18B	Q8IUG5	374

IntAct

12 interactions, top by confidence:

A	B	Type	Score
PELI1	RIMS4	psi-mi:“MI:0915”(physical association)	0.560
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
WDR83	SH2B2	psi-mi:“MI:0914”(association)	0.530
SRPK1	RIMS4	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
WDR83	PIKFYVE	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POM121C	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POTEF	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
PELI1	RIMS4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): RIMS4 (Affinity Capture-MS), RIMS4 (Affinity Capture-MS), RIMS4 (Affinity Capture-RNA), PELI1 (Two-hybrid), RIMS4 (Affinity Capture-MS), RIMS4 (Affinity Capture-MS), RIMS4 (Cross-Linking-MS (XL-MS)), RIMS4 (Affinity Capture-MS), RIMS4 (Two-hybrid), APP (Reconstituted Complex), RIMS4 (Biochemical Activity)

ESM2 similar proteins: A0FGR9, K8FE10, O08835, O15075, O45782, P21521, P23678, P24507, P36582, P40749, P47708, P47709, P50232, P51813, P58069, P60191, P70169, P70610, P97610, Q04861, Q06846, Q14184, Q14644, Q15283, Q5DTI8, Q5M7N9, Q5RJH2, Q60629, Q63713, Q69ZN7, Q6PGN3, Q76II0, Q7L8C5, Q8IV01, Q8N568, Q8VHQ7, Q920N7, Q925B5, Q96C24, Q9BT88

Diamond homologs: A0FGR8, A0FGR9, A6QP06, A8KBH6, O00443, O00445, O00750, O08835, P05126, P05128, P05129, P05130, P05771, P05772, P10102, P10829, P13677, P17252, P41823, P47861, P60191, P63318, P63319, P68403, P68404, P90980, Q22366, Q25378, Q3TZZ7, Q3U7R1, Q4R4U2, Q4VX76, Q5DTI8, Q5FWL4, Q5M7N9, Q5RAG2, Q5RAY1, Q61194, Q62746, Q7ZWU7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	14
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4682965	GRCh37/hg19 20q11.21-13.12(chr20:31010829-44560369)x1	Pathogenic

SpliceAI

906 predictions. Top by Δscore:

Variant	Effect	Δscore
20:44756349:TCAC:T	acceptor_gain	1.0000
20:44756349:TCACC:T	acceptor_loss	1.0000
20:44756350:CACC:C	acceptor_gain	1.0000
20:44756350:CACCT:C	acceptor_loss	1.0000
20:44756353:C:CA	acceptor_loss	1.0000
20:44756353:C:CC	acceptor_gain	1.0000
20:44756354:T:A	acceptor_loss	1.0000
20:44757033:GGCCG:G	acceptor_gain	1.0000
20:44757034:GCCG:G	acceptor_gain	1.0000
20:44757035:CCG:C	acceptor_gain	1.0000
20:44757035:CCGC:C	acceptor_gain	1.0000
20:44757036:CG:C	acceptor_gain	1.0000
20:44757036:CGC:C	acceptor_gain	1.0000
20:44757037:GC:G	acceptor_loss	1.0000
20:44757038:C:CC	acceptor_gain	1.0000
20:44757038:CT:C	acceptor_loss	1.0000
20:44757039:T:A	acceptor_loss	1.0000
20:44757769:CCC:C	acceptor_gain	1.0000
20:44757770:CCC:C	acceptor_gain	1.0000
20:44758067:CTCA:C	donor_loss	1.0000
20:44758068:TCA:T	donor_loss	1.0000
20:44758069:CA:C	donor_loss	1.0000
20:44758070:A:AC	donor_gain	1.0000
20:44758070:A:AT	donor_loss	1.0000
20:44758070:AC:A	donor_gain	1.0000
20:44758070:ACC:A	donor_gain	1.0000
20:44758071:C:CC	donor_gain	1.0000
20:44758071:CC:C	donor_gain	1.0000
20:44758071:CCC:C	donor_gain	1.0000
20:44758071:CCCA:C	donor_gain	1.0000

AlphaMissense

1739 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:44756240:A:G	L235P	1.000
20:44756240:A:T	L235H	1.000
20:44756247:A:C	Y233D	1.000
20:44756303:C:A	G214V	1.000
20:44756303:C:T	G214D	1.000
20:44756304:C:A	G214C	1.000
20:44756304:C:G	G214R	1.000
20:44756343:A:G	W201R	1.000
20:44756343:A:T	W201R	1.000
20:44756902:A:G	L196P	1.000
20:44756929:A:G	F187S	1.000
20:44757016:A:G	L158P	1.000
20:44757024:C:A	K155N	1.000
20:44757024:C:G	K155N	1.000
20:44757026:T:C	K155E	1.000
20:44757702:A:G	L140P	1.000
20:44757711:G:T	A137D	1.000
20:44757732:A:G	L130S	1.000
20:44757771:C:T	G117E	1.000
20:44758072:C:A	G117W	1.000
20:44758072:C:G	G117R	1.000
20:44758072:C:T	G117R	1.000
20:44758120:C:G	G101R	1.000
20:44758120:C:T	G101R	1.000
20:44756236:G:C	F236L	0.999
20:44756236:G:T	F236L	0.999
20:44756237:A:G	F236S	0.999
20:44756238:A:G	F236L	0.999
20:44756240:A:C	L235R	0.999
20:44756246:T:G	Y233S	0.999

dbSNP variants (sampled 300 via entrez): RS1000058770 (20:44803797 C>T), RS1000068025 (20:44752084 T>C,G), RS1000161056 (20:44803905 T>C,G), RS1000166848 (20:44758268 A>G), RS1000218271 (20:44757939 G>A), RS1000275574 (20:44806430 C>G), RS1000290679 (20:44769617 G>A,C), RS1000290890 (20:44788367 T>C), RS1000374091 (20:44764546 G>A), RS1000412956 (20:44775000 C>T), RS1000502046 (20:44756551 G>A), RS1000590765 (20:44798562 T>C,G), RS1000591721 (20:44811508 C>A), RS1000593002 (20:44805112 G>C), RS1000656091 (20:44763349 C>T)

Disease associations

OMIM: gene MIM:611601 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001762_470	Obesity-related traits	5.000000e-07
GCST008555_5	Breakfast cereal skipping frequency	3.000000e-08
GCST008556_5	Breakfast skipping	3.000000e-08
GCST010143_33	Meat-related diet	9.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004626	IGFBP-3 measurement
EFO:0010129	breakfast skipping measurement
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression, increases expression	3
bisphenol A	decreases methylation, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
OTX015	increases expression	1
mivebresib	increases expression	1
propionaldehyde	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
butyraldehyde	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
beta-methylcholine	affects expression	1
pentanal	increases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Aldehydes	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Cisplatin	affects cotreatment, decreases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Tobacco Smoke Pollution	increases methylation	1

Clinical trials (associated diseases)

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