RGS7BP

Summary

RGS7BP (regulator of G protein signaling 7 binding protein, HGNC:23271) is a protein-coding gene on chromosome 5q12.3, encoding Regulator of G-protein signaling 7-binding protein (Q6MZT1). Regulator of G protein-coupled receptor (GPCR) signaling.

This gene encodes a protein that binds to all members of the R7 subfamily of regulators of G protein signaling and regulates their translocation between the nucleus and the plasma membrane. The encoded protein could be regulated by reversible palmitoylation, which anchors it to the plasma membrane. Depalmitoylation localizes the protein to the nucleus. Polymorphisms in this gene may be associated with risk of aspirin-exacerbated respiratory disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 401190 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_001029875

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23271
Approved symbol	RGS7BP
Name	regulator of G protein signaling 7 binding protein
Location	5q12.3
Locus type	gene with protein product
Status	Approved
Aliases	R7BP
Ensembl gene	ENSG00000186479
Ensembl biotype	protein_coding
OMIM	610890
Entrez	401190

Gene structure

Transcript identifiers

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

ENST00000334025, ENST00000505263, ENST00000508162

RefSeq mRNA: 3 — MANE Select: NM_001029875 NM_001029875, NM_001271890, NM_001271891

CCDS: CCDS34170

Canonical transcript exons

ENST00000334025 — 6 exons

Exon	Start	End
ENSE00001331161	64507711	64507877
ENSE00001331166	64609161	64612319
ENSE00001331169	64506015	64506789
ENSE00003551443	64575774	64575904
ENSE00003598400	64598365	64598435
ENSE00003640938	64594710	64594857

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 96.67.

FANTOM5 (CAGE): breadth broad, TPM avg 4.8997 / max 344.4867, expressed in 368 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56664	2.4952	267
56670	0.5688	201
56674	0.3367	66
56663	0.2695	96
56669	0.2586	118
56665	0.2193	105
56662	0.1734	89
56661	0.1222	80
56668	0.0999	53
56672	0.0817	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	96.67	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.63	gold quality
primary visual cortex	UBERON:0002436	90.61	gold quality
prefrontal cortex	UBERON:0000451	88.95	gold quality
occipital lobe	UBERON:0002021	88.49	gold quality
middle temporal gyrus	UBERON:0002771	87.28	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.21	gold quality
lateral globus pallidus	UBERON:0002476	87.15	gold quality
frontal cortex	UBERON:0001870	83.44	gold quality
entorhinal cortex	UBERON:0002728	82.80	gold quality
neocortex	UBERON:0001950	81.98	gold quality
dorsal root ganglion	UBERON:0000044	81.92	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.58	gold quality
superior frontal gyrus	UBERON:0002661	81.37	gold quality
cerebral cortex	UBERON:0000956	79.94	gold quality
buccal mucosa cell	CL:0002336	79.78	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.64	gold quality
parietal lobe	UBERON:0001872	79.33	gold quality
substantia nigra pars reticulata	UBERON:0001966	79.03	gold quality
substantia nigra pars compacta	UBERON:0001965	78.93	gold quality
postcentral gyrus	UBERON:0002581	78.78	gold quality
cerebellar vermis	UBERON:0004720	78.23	gold quality
putamen	UBERON:0001874	77.42	gold quality
cortical plate	UBERON:0005343	77.38	gold quality
anterior cingulate cortex	UBERON:0009835	77.10	gold quality
right frontal lobe	UBERON:0002810	76.22	gold quality
caudate nucleus	UBERON:0001873	76.18	gold quality
forebrain	UBERON:0001890	75.02	gold quality
right coronary artery	UBERON:0001625	74.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

196 targeting RGS7BP, 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-5692A	100.00	74.40	6850
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-302C-5P	99.97	72.56	3642

Literature-anchored findings (GeneRIF, showing 6)

• cytoplasmic RGS7*Gbeta5*R7BP heterotrimers and RGS7*Gbeta5 heterodimers are equivalently inefficient regulators of G protein-coupled receptor signaling relative to plasma membrane-bound heterotrimers bearing palmitoylated R7BP. (PMID:16867977)
• the successful purification of functionally intact Gbeta5-free recombinant RGS11 was reported that differentially interact with R7BP and Galpha(oa). (PMID:19497306)
• BL3-ht2 of RGS7BP may be an important genetic variant associated with AERD. The haplotype of block 3 may play a protective role against aspirin hypersensitivity in asthma, perhaps by altering the responsiveness of muscarinic receptors. (PMID:21457877)
• R7-binding protein had a strong inhibitory effect on homo-oligomerization of RGS7. (PMID:26895961)
• Data (including data from studies using transgenic mice) suggest that R7BP-RGS7 heterotrimers interact with Galpha13 to augment signaling pathways in neurons that regulate neurite morphogenesis. (R7BP = RGS7 family binding protein; RGS7 = regulator of G-protein signaling 7 protein; Galpha13 = GTP-binding protein alpha subunit 13) (PMID:28432124)
• Data mapped differences in deuterium exchange between the regulator of G protein signaling 7 (RGS7)-Gbeta5 protein(Gbeta5)-RGS7 family binding protein (R7BP) trimer and the RGS7-Gbeta5 dimer. (PMID:30540250)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rgs7bpb	ENSDARG00000016742
danio_rerio	rgs7bpa	ENSDARG00000060601
mus_musculus	Rgs7bp	ENSMUSG00000021719
rattus_norvegicus	Rgs7bp	ENSRNOG00000013389
drosophila_melanogaster	CG14340	FBGN0031302
drosophila_melanogaster	dcma	FBGN0085380

Paralogs (1): RGS9BP (ENSG00000186326)

Protein

Protein identifiers

Regulator of G-protein signaling 7-binding protein — Q6MZT1 (reviewed: Q6MZT1)

Alternative names: R7 family-binding protein

All UniProt accessions (1): Q6MZT1

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of G protein-coupled receptor (GPCR) signaling. Regulatory subunit of the R7-Gbeta5 complexes that acts by controlling the subcellular location of the R7-Gbeta5 complexes. When palmitoylated, it targets the R7-Gbeta5 complexes to the plasma membrane, leading to inhibit G protein alpha subunits. When it is unpalmitoylated, the R7-Gbeta5 complexes undergo a nuclear/cytoplasmic shuttling. May also act by controlling the proteolytic stability of R7 proteins, probably by protecting them from degradation.

Subunit / interactions. Interacts with ‘R7’ family proteins RGS6, RGS7, RGS9 and RGS11. Component of some R7-Gbeta5 complex composed of some R7 protein (RGS6, RGS7, RGS9 or RGS11), Gbeta5 (GNB5) and RGS7BP.

Subcellular location. Nucleus. Cytoplasm. Cell membrane.

Post-translational modifications. Palmitoylated. Undergoes rapid palmitoylation turnover. De novo and turnover palmitoylation are both mediated by ZDHHC2. Palmitoylation regulates the cell membrane and nuclear shuttling and the regulation of GPCR signaling. Upon depalmitoylation, it is targeted from the plasma membrane into the nucleus. GPCR signaling inhibits depalmitoylation and promotes localization to the plasma membrane.

Domain organisation. The nuclear localization signal is both required for nuclear localization and palmitoylation.

Similarity. Belongs to the RGS7BP/RGS9BP family.

RefSeq proteins (3): NP_001025046, NP_001258819, NP_001258820 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026512	RGS7BP/RGS9BP	Family

UniProt features (9 total): region of interest 2, compositionally biased region 2, lipid moiety-binding region 2, chain 1, short sequence motif 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6MZT1-F1	73.32	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): 252, 253

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 133 (showing top): AAGCAAT_MIR137, TATTATA_MIR374, CTATGCA_MIR153, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, CORRE_MULTIPLE_MYELOMA_UP, ATGCTGG_MIR338, GOCC_NEURON_PROJECTION, chr5q12, CTTTGTA_MIR524, GOCC_POSTSYNAPSE, GOCC_DENDRITIC_SHAFT, GOCC_NEURON_SPINE, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL, GOCC_SYNAPSE, GOCC_POSTSYNAPTIC_MEMBRANE

GO Biological Process (3): G protein-coupled receptor signaling pathway (GO:0007186), negative regulation of signal transduction (GO:0009968), regulation of postsynaptic membrane potential (GO:0060078)

GO Molecular Function (0):

GO Cellular Component (14): nucleus (GO:0005634), cytoplasm (GO:0005737), axon (GO:0030424), presynaptic membrane (GO:0042734), neuron projection (GO:0043005), dendritic shaft (GO:0043198), perikaryon (GO:0043204), dendritic spine head (GO:0044327), postsynapse (GO:0098794), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), plasma membrane (GO:0005886), membrane (GO:0016020), presynapse (GO:0098793)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
synapse	3
signal transduction	2
postsynaptic density	2
G protein-coupled receptor activity	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
regulation of membrane potential	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
neuron projection	1
synaptic membrane	1
presynapse	1
plasma membrane bounded cell projection	1
dendrite	1
neuronal cell body	1
dendritic spine	1
postsynaptic membrane	1
postsynaptic specialization membrane	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1210 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGS7BP	GNB5	O14775	990
RGS7BP	RGS7	P49802	988
RGS7BP	RGS11	O94810	964
RGS7BP	RGS9BP	Q6ZS82	955
RGS7BP	RGS6	P49758	942
RGS7BP	RGS8	P57771	729
RGS7BP	RGS4	P49798	727
RGS7BP	RGS10	O43665	726
RGS7BP	RGS17	Q9UGC6	725
RGS7BP	RGS20	O76081	725
RGS7BP	RGS21	Q2M5E4	723
RGS7BP	RGS13	O14921	720
RGS7BP	RGS12	O14924	720
RGS7BP	RGS18	Q9NS28	720
RGS7BP	RGS19	P49795	703

IntAct

2 interactions, top by confidence:

A	B	Type	Score
DISC1	RGS7BP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): RGS7BP (Affinity Capture-MS), RGS9 (Affinity Capture-Western), GNB5 (Affinity Capture-Western), RGS9 (Co-localization), RGS7BP (Affinity Capture-Western), RGS9 (Co-localization), RGS9 (Affinity Capture-Western), GNB5 (Affinity Capture-Western)

ESM2 similar proteins: A0A571BF63, A0A8M9QN10, A2AHC3, A2ARM1, A7YY97, D3Z8E6, D4AEC2, F1MN90, M0R2J8, O00273, O43149, O54786, O70303, P56198, Q08DH5, Q13009, Q14CH0, Q29RJ0, Q2T9I9, Q3T191, Q3V0J4, Q4R739, Q5EA86, Q5EB20, Q5SSH7, Q5T5Y3, Q5XI33, Q60610, Q61194, Q64512, Q68FS7, Q6GPM0, Q6MZT1, Q6NU51, Q6NV72, Q6NZK8, Q6ZUJ8, Q80WB0, Q8BV79, Q8C636

Diamond homologs: Q08BU8, Q08DH5, Q4V9P3, Q5FVH8, Q6GLU0, Q6GPM0, Q6MZT1, Q8BQP9, Q8MJG0, Q5XHI3, Q6XK22, Q148R9, Q504F3, Q5M8K0, Q6GLX4, Q6ZS82

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1096 predictions. Top by Δscore:

Variant	Effect	Δscore
5:64575766:T:A	acceptor_gain	1.0000
5:64575769:TGCA:T	acceptor_loss	1.0000
5:64575770:GCA:G	acceptor_loss	1.0000
5:64575772:A:AG	acceptor_gain	1.0000
5:64575772:A:G	acceptor_loss	1.0000
5:64575772:AGCCC:A	acceptor_gain	1.0000
5:64575773:G:GT	acceptor_gain	1.0000
5:64575773:GC:G	acceptor_gain	1.0000
5:64575773:GCC:G	acceptor_gain	1.0000
5:64575773:GCCC:G	acceptor_gain	1.0000
5:64575773:GCCCG:G	acceptor_gain	1.0000
5:64598364:GA:G	acceptor_gain	1.0000
5:64506786:GATG:G	donor_gain	0.9900
5:64506789:GGTG:G	donor_loss	0.9900
5:64506790:GTGG:G	donor_loss	0.9900
5:64506791:T:A	donor_loss	0.9900
5:64507710:GCTT:G	acceptor_gain	0.9900
5:64507876:GG:G	donor_gain	0.9900
5:64507877:GG:G	donor_gain	0.9900
5:64532213:G:T	donor_gain	0.9900
5:64575762:A:AG	acceptor_gain	0.9900
5:64575769:T:A	acceptor_gain	0.9900
5:64575900:AAAAG:A	donor_loss	0.9900
5:64575901:AAAGG:A	donor_loss	0.9900
5:64575902:AAGGT:A	donor_loss	0.9900
5:64575903:AG:A	donor_loss	0.9900
5:64575904:GG:G	donor_loss	0.9900
5:64575905:G:GA	donor_loss	0.9900
5:64575906:T:G	donor_loss	0.9900
5:64594695:C:G	acceptor_gain	0.9900

AlphaMissense

1683 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:64507724:T:C	F60S	1.000
5:64507739:C:A	A65D	1.000
5:64507748:G:C	R68P	1.000
5:64507757:T:A	V71D	1.000
5:64575824:T:C	L128P	1.000
5:64575842:T:C	M134T	1.000
5:64575864:A:C	K141N	1.000
5:64575864:A:T	K141N	1.000
5:64575875:T:C	L145P	1.000
5:64598388:T:C	L212P	1.000
5:64598400:T:C	L216P	1.000
5:64507715:T:A	V57D	0.999
5:64507728:C:A	N61K	0.999
5:64507728:C:G	N61K	0.999
5:64507747:C:G	R68G	0.999
5:64507748:G:T	R68L	0.999
5:64507754:T:C	L70P	0.999
5:64507760:T:A	I72N	0.999
5:64507760:T:C	I72T	0.999
5:64507760:T:G	I72S	0.999
5:64507768:G:A	G75R	0.999
5:64507768:G:C	G75R	0.999
5:64507768:G:T	G75W	0.999
5:64507769:G:A	G75E	0.999
5:64507769:G:T	G75V	0.999
5:64507820:G:C	R92T	0.999
5:64507821:A:C	R92S	0.999
5:64507821:A:T	R92S	0.999
5:64507828:G:C	G95R	0.999
5:64507841:C:A	A99D	0.999

dbSNP variants (sampled 300 via entrez): RS1000053645 (5:64504630 C>G), RS1000067699 (5:64585540 A>T), RS1000150694 (5:64559883 A>G), RS1000183583 (5:64559717 C>T), RS1000195840 (5:64605796 A>G), RS1000210229 (5:64516099 C>T), RS1000222086 (5:64541904 A>C,G), RS1000232871 (5:64612238 A>G,T), RS1000238412 (5:64545476 A>C), RS1000284490 (5:64583020 T>C), RS1000308674 (5:64571025 C>A,T), RS1000333759 (5:64510138 A>T), RS1000352328 (5:64599331 C>T), RS1000358851 (5:64563931 T>C), RS1000383477 (5:64599013 T>A,C)

Disease associations

OMIM: gene MIM:610890 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004904_22	Body mass index	6.000000e-09
GCST007576_62	Chronotype	5.000000e-12
GCST010989_249	Body size at age 10	4.000000e-19

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008328	chronotype measurement
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
bisphenol A	decreases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Allergens	affects cotreatment, increases abundance, increases expression	1
Aspirin	affects response to substance	1
Vehicle Emissions	affects cotreatment, increases abundance, increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Vanadates	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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