RIMBP2

Summary

RIMBP2 (RIMS binding protein 2, HGNC:30339) is a protein-coding gene on chromosome 12q24.33, encoding RIMS-binding protein 2 (O15034). Plays a role in the synaptic transmission as bifunctional linker that interacts simultaneously with RIMS1, RIMS2, CACNA1D and CACNA1B.

Predicted to enable voltage-gated calcium channel activity involved in regulation of presynaptic cytosolic calcium levels and voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential. Predicted to be a structural constituent of presynaptic active zone. Predicted to be involved in neuromuscular synaptic transmission; regulation of calcium-dependent activation of synaptic vesicle fusion; and regulation of presynaptic membrane potential. Predicted to be located in plasma membrane and synapse. Predicted to be active in calyx of Held; glutamatergic synapse; and presynaptic active zone cytoplasmic component.

Source: NCBI Gene 23504 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 155 total
• MANE Select transcript: NM_001393629

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30339
Approved symbol	RIMBP2
Name	RIMS binding protein 2
Location	12q24.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0318, RBP2, MGC15831, RIM-BP2, PPP1R133
Ensembl gene	ENSG00000060709
Ensembl biotype	protein_coding
OMIM	611602
Entrez	23504

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 14 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron

ENST00000261655, ENST00000535703, ENST00000536632, ENST00000540658, ENST00000541840, ENST00000544568, ENST00000643940, ENST00000644209, ENST00000647475, ENST00000685265, ENST00000688340, ENST00000689851, ENST00000690449, ENST00000690669, ENST00000691977, ENST00000707118, ENST00000908656, ENST00000908657, ENST00000964721, ENST00000964722

RefSeq mRNA: 25 — MANE Select: NM_001393629 NM_001351226, NM_001351227, NM_001351228, NM_001351229, NM_001351230, NM_001351231, NM_001351232, NM_001351233, NM_001393614, NM_001393615, NM_001393616, NM_001393617, NM_001393618, NM_001393619, NM_001393620, NM_001393621, NM_001393622, NM_001393623, NM_001393624, NM_001393625, NM_001393626, NM_001393627, NM_001393628, NM_001393629, NM_015347

CCDS: CCDS31925, CCDS91774, CCDS91775, CCDS91776, CCDS91777

Canonical transcript exons

ENST00000690449 — 23 exons

Exon	Start	End
ENSE00000757516	130414125	130414306
ENSE00000757517	130422453	130422561
ENSE00000757518	130428179	130428337
ENSE00000757519	130434734	130434880
ENSE00000757520	130436842	130437291
ENSE00000757521	130438365	130438516
ENSE00000757523	130441848	130442660
ENSE00000757527	130451195	130451340
ENSE00000903691	130407726	130407829
ENSE00000903693	130412619	130412787
ENSE00000938260	130450200	130450276
ENSE00000938261	130445160	130445269
ENSE00001121163	130506648	130506770
ENSE00002212228	130628322	130628456
ENSE00002290614	130517828	130517917
ENSE00003572038	130406172	130406243
ENSE00003592262	130399679	130399813
ENSE00003619584	130456496	130456700
ENSE00003666192	130478912	130479016
ENSE00003819391	130424142	130424858
ENSE00003822131	130470693	130470743
ENSE00003930688	130716222	130716299
ENSE00003938551	130396133	130397549

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 96.82.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6556 / max 260.5898, expressed in 302 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134170	2.3486	269
134172	0.5389	103
134166	0.2847	83
134165	0.2458	54
134171	0.1127	50
134167	0.0661	40
134164	0.0587	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	96.82	gold quality
frontal pole	UBERON:0002795	95.42	gold quality
pituitary gland	UBERON:0000007	92.88	gold quality
CA1 field of hippocampus	UBERON:0003881	91.40	gold quality
adenohypophysis	UBERON:0002196	91.24	gold quality
orbitofrontal cortex	UBERON:0004167	91.07	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.95	gold quality
superior frontal gyrus	UBERON:0002661	90.72	gold quality
prefrontal cortex	UBERON:0000451	90.36	gold quality
middle temporal gyrus	UBERON:0002771	90.34	gold quality
postcentral gyrus	UBERON:0002581	89.92	gold quality
entorhinal cortex	UBERON:0002728	89.87	gold quality
islet of Langerhans	UBERON:0000006	89.62	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.15	gold quality
frontal cortex	UBERON:0001870	89.00	gold quality
parietal lobe	UBERON:0001872	88.73	gold quality
neocortex	UBERON:0001950	88.08	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.77	gold quality
middle frontal gyrus	UBERON:0002702	87.25	gold quality
cerebral cortex	UBERON:0000956	87.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.80	gold quality
cingulate cortex	UBERON:0003027	86.63	gold quality
anterior cingulate cortex	UBERON:0009835	86.62	gold quality
right uterine tube	UBERON:0001302	86.07	gold quality
primary visual cortex	UBERON:0002436	85.87	gold quality
right frontal lobe	UBERON:0002810	85.64	gold quality
Ammon’s horn	UBERON:0001954	84.51	gold quality
occipital lobe	UBERON:0002021	84.46	gold quality
forebrain	UBERON:0001890	84.25	gold quality
temporal lobe	UBERON:0001871	84.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

232 targeting RIMBP2, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 2)

• RIMBP2 is identified in humans (PMID:17855024)
• TCF4 Mutations Disrupt Synaptic Function Through Dysregulation of RIMBP2 in Patient-Derived Cortical Neurons. (PMID:37573005)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rimbp2b	ENSDARG00000001154
danio_rerio	rimbp2a	ENSDARG00000104101
mus_musculus	Rimbp2	ENSMUSG00000029420
rattus_norvegicus	Rimbp2	ENSRNOG00000022893
drosophila_melanogaster	Rbp	FBGN0262483
caenorhabditis_elegans		WBGENE00006513

Paralogs (4): TSPOAP1 (ENSG00000005379), RIMBP3C (ENSG00000183246), RIMBP3B (ENSG00000274600), RIMBP3 (ENSG00000275793)

Protein

Protein identifiers

RIMS-binding protein 2 — O15034 (reviewed: O15034)

All UniProt accessions (12): O15034, A0A2R8Y5H8, A0A2R8Y6Z0, A0A2R8YF94, A0A2R8YFN7, A0A2U3TZP8, A0A8I5KQF3, A0A8I5KV98, A0A8I5KWW4, A0A8I5QJU8, A0A9L9PY66, H0YFN4

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the synaptic transmission as bifunctional linker that interacts simultaneously with RIMS1, RIMS2, CACNA1D and CACNA1B.

Subunit / interactions. Interacts with RIMS1, RIMS2, CACNA1D and CACNA1B, and potentially with other Ca(2+) channel alpha-1 isoforms.

Subcellular location. Cell membrane. Synapse.

Domain organisation. The SH3 domains mediate binding to a proline-rich motif in RIMS1, RIMS2, CACNA1D and CACNA1B.

Similarity. Belongs to the RIMBP family.

Isoforms (3)

UniProt ID	Names	Canonical?
O15034-1	1	yes
O15034-2	2
O15034-3	3

RefSeq proteins (25): NP_001338155, NP_001338156, NP_001338157, NP_001338158, NP_001338159, NP_001338160, NP_001338161, NP_001338162, NP_001380543, NP_001380544, NP_001380545, NP_001380546, NP_001380547, NP_001380548, NP_001380549, NP_001380550, NP_001380551, NP_001380552, NP_001380553, NP_001380554, NP_001380555, NP_001380556, NP_001380557, NP_001380558, NP_056162 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR035753	RIM-BP_SH3_2	Domain
IPR035755	RIM-BP_SH3_3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR040325	RIMBP1/2/3	Family
IPR057884	FN3_RIM-BP1/2/3	Domain

Pfam: PF00041, PF07653, PF14604, PF25523

UniProt features (64 total): strand 22, region of interest 7, domain 6, turn 6, modified residue 5, splice variant 5, helix 5, compositionally biased region 4, sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1WIE	SOLUTION NMR
2CSI	SOLUTION NMR
2CSP	SOLUTION NMR
2CSQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15034-F1	66.47	0.31

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 (5): 704, 712, 832, 839, 841

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 196 (showing top): GCAAGGA_MIR502, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_ACID_TRANSPORT, COUP_01, NF1_Q6_01, GOBP_ORGANIC_ANION_TRANSPORT, HFH3_01, HNF4_01, PPAR_DR1_Q2, GOBP_SYNAPTIC_SIGNALING, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_LIPID_METABOLIC_PROCESS, SANSOM_APC_TARGETS_DN, TATA_C, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT

GO Biological Process (1): neuromuscular synaptic transmission (GO:0007274)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), synapse (GO:0045202), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chemical synaptic transmission	1
binding	1
membrane	1
cell periphery	1
cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

964 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIMBP2	RIMS1	Q86UR5	955
RIMBP2	RIMS2	Q9UQ26	951
RIMBP2	RAB3C	Q96E17	827
RIMBP2	UNC13B	O14795	758
RIMBP2	RAB3A	P20336	744
RIMBP2	TSPO	P30536	658
RIMBP2	CACNA1A	P78510	636
RIMBP2	UNC13A	Q9UPW8	629
RIMBP2	ERC1	Q8IUD2	627
RIMBP2	PPFIA3	O75145	566
RIMBP2	CACNA1D	Q01668	532
RIMBP2	MYRIP	Q8NFW9	513
RIMBP2	TSPOAP1	O95153	495
RIMBP2	SHANK2	Q9UPX8	494
RIMBP2	ARSG	Q96EG1	474

IntAct

8 interactions, top by confidence:

A	B	Type	Score
ADAM10	RIMBP2	psi-mi:“MI:0407”(direct interaction)	0.440
ADAM12	RIMBP2	psi-mi:“MI:0407”(direct interaction)	0.440
PPP1CA	RIMBP2	psi-mi:“MI:0407”(direct interaction)	0.440
RIMBP2	CACNA1A	psi-mi:“MI:0915”(physical association)	0.370
ECE1	RIMBP2	psi-mi:“MI:0915”(physical association)	0.370
USP3	EIF3F	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): NAA10 (Two-hybrid), RIMBP2 (Negative Genetic), RIMBP2 (Protein-RNA), RIMBP2 (Positive Genetic), RIMBP2 (Affinity Capture-MS), SMC4 (Cross-Linking-MS (XL-MS)), RIMBP2 (Affinity Capture-MS), RIMBP2 (Two-hybrid), RIMBP2 (Affinity Capture-Western)

ESM2 similar proteins: A0JN71, A4IFK0, A5PMU4, A6QQV9, O15034, O15040, O62666, O62674, O62675, O62676, O62677, O62678, O75995, P49796, P52734, P59672, P78314, P97432, P98174, Q06649, Q0V8R5, Q13905, Q14596, Q3U0J8, Q501R9, Q53GL0, Q5BJM5, Q5F3C8, Q5RC94, Q5SUE8, Q6AI12, Q6ZMT1, Q7Z5H3, Q80U40, Q80UZ0, Q80XA6, Q80YS6, Q8BL80, Q8K352, Q8N556

Diamond homologs: A0A0K3AV08, A1CEK6, A1DFN5, E2RP94, O15034, O95153, P19706, Q15811, Q4WHP5, Q557J6, Q5BBL4, Q7TNF8, Q80U40, Q8QFX1, Q8R550, Q925Q9, Q96B97, Q9JIR0, Q9JIR1, A6NJZ7, A6NNM3, Q9UFD9, M0R4F8, Q6XJU9, Q6XZF7, A2QW93, Q0CJU8, Q3V0F0, A1Z7A6, A4FU49, A4RF61, A5D7F8, B1V8A0, D3ZG83, E9Q634, F1LRS8, O00160, O35179, O35180, O35413

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RIMBP2	“down-regulates activity”	RIMS1	binding
RIMBP2	“down-regulates activity”	RIMS2	binding
RIMBP2	“down-regulates activity”	RIMS3	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	126
Likely benign	15
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

5139 predictions. Top by Δscore:

Variant	Effect	Δscore
12:130406165:AACTT:A	donor_loss	1.0000
12:130406166:ACTTA:A	donor_loss	1.0000
12:130406167:CT:C	donor_loss	1.0000
12:130406168:T:TA	donor_loss	1.0000
12:130406170:A:AC	donor_gain	1.0000
12:130406170:A:AT	donor_loss	1.0000
12:130406171:C:CC	donor_gain	1.0000
12:130406171:CATA:C	donor_gain	1.0000
12:130406240:CGGC:C	acceptor_gain	1.0000
12:130406241:GGCC:G	acceptor_loss	1.0000
12:130406242:GCCT:G	acceptor_loss	1.0000
12:130406243:CCTG:C	acceptor_loss	1.0000
12:130406244:C:CC	acceptor_gain	1.0000
12:130406244:C:G	acceptor_loss	1.0000
12:130406245:T:G	acceptor_loss	1.0000
12:130407840:C:CT	acceptor_gain	1.0000
12:130407843:A:T	acceptor_gain	1.0000
12:130412613:GCTTA:G	donor_loss	1.0000
12:130412614:CTTA:C	donor_loss	1.0000
12:130412615:TTA:T	donor_loss	1.0000
12:130412616:TAC:T	donor_loss	1.0000
12:130412617:A:C	donor_loss	1.0000
12:130412618:C:A	donor_loss	1.0000
12:130412783:TAAAC:T	acceptor_gain	1.0000
12:130412784:AAAC:A	acceptor_gain	1.0000
12:130412785:AAC:A	acceptor_gain	1.0000
12:130412786:AC:A	acceptor_gain	1.0000
12:130412786:ACCTA:A	acceptor_loss	1.0000
12:130412787:CC:C	acceptor_gain	1.0000
12:130412788:C:CC	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000021542 (12:130539891 G>A,T), RS1000027585 (12:130636347 C>T), RS1000042513 (12:130651663 G>A), RS1000046321 (12:130505003 C>T), RS1000063648 (12:130495585 GTAA>G), RS1000077564 (12:130546023 G>A), RS1000097838 (12:130615156 TTATATTG>T), RS1000098911 (12:130560772 C>G,T), RS1000104816 (12:130685207 C>T), RS1000113662 (12:130422707 G>A,T), RS1000115471 (12:130706854 T>C), RS1000118106 (12:130665505 C>T), RS1000123380 (12:130453657 C>T), RS1000126664 (12:130423225 G>A,T), RS1000159050 (12:130555700 A>T)

Disease associations

OMIM: gene MIM:611602 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001285_9	Psychosis and Alzheimer’s disease	8.000000e-06
GCST002846_4	Lifespan	1.000000e-08
GCST005440_17	Alcohol dependence symptom count	6.000000e-10
GCST006035_8	Breast cancer and/or colorectal cancer	6.000000e-06
GCST006460_10	Bronchopulmonary dysplasia in preterm infants	5.000000e-06
GCST008477_16	Emphysema annual change measurement in smokers (adjusted lung density)	6.000000e-06
GCST010002_178	Refractive error	1.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005940	psychotic symptoms
EFO:0007835	alcohol dependence measurement
EFO:0007626	emphysema imaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	8
bisphenol A	affects methylation, affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation	2
Nickel	decreases expression	2
Aflatoxin B1	increases methylation	2
methylmercuric chloride	decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases 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	1
dorsomorphin	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Lead	affects expression	1
Malathion	decreases expression	1
Phthalic Acids	decreases methylation	1
Progesterone	increases expression	1
Tobacco Smoke Pollution	increases methylation	1
Tretinoin	increases expression	1
Magnetite Nanoparticles	increases expression	1

Clinical trials (associated diseases)

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