GPRASP3

Summary

GPRASP3 (G protein-coupled receptor associated sorting protein family member 3, HGNC:29353) is a protein-coding gene on chromosome Xq22.1, encoding G protein-coupled receptor associated sorting protein 3 (Q6PI77). Survival and differentiation promoting protein that plays a role in the regulation of neurosynaptogenesis.

This gene is a member of a gene family which encodes proteins with a basic helix-loop-helix domain. Other members of this gene family encode proteins which function as transcription factors, either enhancing or inhibiting transcription depending on the activity of other DNA binding proteins. The coding region of this gene is located entirely within the terminal exon. The encoded protein may be involved in the survival of neurons (PMID: 15034937). Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 80823 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 4 total — 1 pathogenic
• MANE Select transcript: NM_001142524

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29353
Approved symbol	GPRASP3
Name	G protein-coupled receptor associated sorting protein family member 3
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	p60TRP, KIAA1701, GASP3
Ensembl gene	ENSG00000198908
Ensembl biotype	protein_coding
OMIM	300921
Entrez	80823

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000361229, ENST00000372735, ENST00000447531, ENST00000448867, ENST00000457056, ENST00000483294, ENST00000486988, ENST00000862730, ENST00000922641

RefSeq mRNA: 8 — MANE Select: NM_001142524 NM_001142524, NM_001142525, NM_001142526, NM_001142527, NM_001142528, NM_001142529, NM_001142530, NM_030639

Canonical transcript exons

ENST00000457056 — 4 exons

Exon	Start	End
ENSE00001359890	102720957	102721091
ENSE00001458491	102748699	102753540
ENSE00001458492	102747817	102747911
ENSE00001790092	102720743	102720825

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 87.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.2085 / max 215.3042, expressed in 1201 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196993	1.9392	793
196992	1.1570	575
196995	0.4216	158
196994	0.4021	214
196996	0.2886	133

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	87.20	gold quality
ganglionic eminence	UBERON:0004023	86.50	gold quality
ventricular zone	UBERON:0003053	84.80	gold quality
superior frontal gyrus	UBERON:0002661	83.86	gold quality
prefrontal cortex	UBERON:0000451	83.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.11	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.52	gold quality
frontal cortex	UBERON:0001870	80.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.10	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.03	gold quality
cerebral cortex	UBERON:0000956	79.24	gold quality
primary visual cortex	UBERON:0002436	79.24	gold quality
islet of Langerhans	UBERON:0000006	78.56	gold quality
anterior cingulate cortex	UBERON:0009835	78.15	gold quality
hypothalamus	UBERON:0001898	77.57	gold quality
stromal cell of endometrium	CL:0002255	76.81	gold quality
brain	UBERON:0000955	76.63	gold quality
corpus callosum	UBERON:0002336	76.33	gold quality
cerebellum	UBERON:0002037	76.26	gold quality
right frontal lobe	UBERON:0002810	76.14	gold quality
cerebellar cortex	UBERON:0002129	76.10	gold quality
nucleus accumbens	UBERON:0001882	76.03	gold quality
cerebellar hemisphere	UBERON:0002245	75.94	gold quality
smooth muscle tissue	UBERON:0001135	75.02	gold quality
endometrium	UBERON:0001295	74.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	74.31	gold quality
Ammon’s horn	UBERON:0001954	74.29	gold quality
temporal lobe	UBERON:0001871	73.92	gold quality
caudate nucleus	UBERON:0001873	73.91	gold quality
amygdala	UBERON:0001876	73.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HOXD1

miRNA regulators (miRDB)

79 targeting GPRASP3, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-3177-5P	99.65	70.38	1174

Literature-anchored findings (GeneRIF, showing 2)

• Down-regulation in the brain of Alzheimer’s disease subjects point to a possible pivotal role of p60TRP in the control of cellular aging and survival. (PMID:15034937)
• Report that some regions of p60TRP were more prone to specific mutations, with two hotspots for mutations at E15 and E171. (PMID:26854063)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	armc10	ENSDARG00000062960
mus_musculus	Bhlhb9	ENSMUSG00000072964
rattus_norvegicus	Gprasp3	ENSRNOG00000003191
caenorhabditis_elegans		WBGENE00013456

Paralogs (10): ARMCX3 (ENSG00000102401), ARMCX5 (ENSG00000125962), ARMCX1 (ENSG00000126947), ARMC12 (ENSG00000157343), GPRASP2 (ENSG00000158301), ARMC10 (ENSG00000170632), ARMCX2 (ENSG00000184867), ARMCX4 (ENSG00000196440), GPRASP1 (ENSG00000198932), ARMCX6 (ENSG00000198960)

Protein

Protein identifiers

G protein-coupled receptor associated sorting protein 3 — Q6PI77 (reviewed: Q6PI77)

Alternative names: Protein BHLHb9, Transcription regulator of 60 kDa

All UniProt accessions (1): Q6PI77

UniProt curated annotations — full annotation on UniProt →

Function. Survival and differentiation promoting protein that plays a role in the regulation of neurosynaptogenesis. Induces phosphatase PP2A activity which results in APP dephosphorylation and inhibits BACE1-mediated processing of APP.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Highly expressed in brain. Not expressed in lung or liver. Down-regulated in brain from patients suffering from Alzheimer disease.

Induction. Down-regulated in colon cancer cells, due to CpG hypermethylation of its promoter.

Similarity. Belongs to the GPRASP family.

RefSeq proteins (8): NP_001135996, NP_001135997, NP_001135998, NP_001135999, NP_001136000, NP_001136001, NP_001136002, NP_085142 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006911	ARM-rpt_dom	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR043374	GASP1-3	Family

Pfam: PF04826

UniProt features (6 total): region of interest 2, sequence variant 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PI77-F1	60.00	0.22

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 159 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (5): learning or memory (GO:0007611), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of neurogenesis (GO:0050769), positive regulation of synapse assembly (GO:0051965), positive regulation of dendritic spine morphogenesis (GO:0061003)

GO Molecular Function (2): protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of nervous system development	2
cellular anatomical structure	2
behavior	1
cognition	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
positive regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
synapse assembly	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
positive regulation of neuron projection development	1
positive regulation of dendrite morphogenesis	1
dendritic spine morphogenesis	1
positive regulation of dendritic spine development	1
regulation of dendritic spine morphogenesis	1
identical protein binding	1
protein dimerization activity	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPRASP3	IPO5	O00410	571
GPRASP3	ADGRL1	O94910	492
GPRASP3	DIXDC1	Q155Q3	478
GPRASP3	FZD4	Q9ULV1	432
GPRASP3	ADGRL2	O95490	423
GPRASP3	SLC38A12	Q8NE00	369
GPRASP3	SPCS3	P12280	355
GPRASP3	ADGRL3	Q9HAR2	351
GPRASP3	IFRD1	O00458	346
GPRASP3	FLRT2	O43155	323
GPRASP3	KLHL1	Q9NR64	316
GPRASP3	ZNF775	Q96BV0	310
GPRASP3	AGFG2	O95081	299
GPRASP3	DSTYK	Q6XUX3	281
GPRASP3	MFSD6	Q6ZSS7	276

IntAct

204 interactions, top by confidence:

A	B	Type	Score
MLF1	DNAJB6	psi-mi:“MI:0914”(association)	0.750
GPRASP3	ENKD1	psi-mi:“MI:0915”(physical association)	0.560
GPRASP3	SMARCD1	psi-mi:“MI:0915”(physical association)	0.560
GPRASP3	ATOSB	psi-mi:“MI:0915”(physical association)	0.560
POLR1C	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
GPRASP3	SH3KBP1	psi-mi:“MI:0915”(physical association)	0.560
MYO15B	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
TOP3B	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
GPRASP3	PRPF31	psi-mi:“MI:0915”(physical association)	0.560
GPRASP3	SCNM1	psi-mi:“MI:0915”(physical association)	0.560
GAS8	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
GPRASP3	ANKRD11	psi-mi:“MI:0915”(physical association)	0.560
KLHL38	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
GPRASP3	ZNF417	psi-mi:“MI:0915”(physical association)	0.560
GPRASP3	PNMA5	psi-mi:“MI:0915”(physical association)	0.560
SPANXN2	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
PHF1	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
GPRASP3	TEPSIN	psi-mi:“MI:0915”(physical association)	0.560
PRKAB2	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
GPANK1	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
GPRASP3	MISP	psi-mi:“MI:0915”(physical association)	0.560
TSGA10IP	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
GPRASP3	INO80B	psi-mi:“MI:0915”(physical association)	0.560
GPRASP3	SRCAP	psi-mi:“MI:0915”(physical association)	0.560
DDX6	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
CDC37	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
LMO1	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
GPRASP3	THOC1	psi-mi:“MI:0915”(physical association)	0.560
USP20	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
GPRASP3	FAM124B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (70): BHLHB9 (Two-hybrid), BHLHB9 (Two-hybrid), BHLHB9 (Two-hybrid), BHLHB9 (Two-hybrid), BHLHB9 (Two-hybrid), BHLHB9 (Two-hybrid), BHLHB9 (Two-hybrid), BHLHB9 (Two-hybrid), BHLHB9 (Two-hybrid), BHLHB9 (Two-hybrid), BHLHB9 (Two-hybrid), BHLHB9 (Two-hybrid), BHLHB9 (Two-hybrid), BHLHB9 (Two-hybrid), BHLHB9 (Two-hybrid)

ESM2 similar proteins: A0JPK3, A1YFX5, A2RQG7, A7KBS4, F4JUI3, G3X9G7, O49498, P03131, P04605, P04614, P05909, P0C1K0, P11332, P12453, P18098, P24109, P35965, P98182, Q09424, Q0VCB0, Q19203, Q2YDJ5, Q3UZB0, Q567C6, Q5BI31, Q5EXX3, Q5M948, Q62396, Q6AXY9, Q6PB60, Q6PI77, Q71HP2, Q74124, Q7JUR5, Q7Z142, Q7Z2Y5, Q80YD3, Q86UQ0, Q8C0P7, Q8C6P8

Diamond homologs: B1WBW4, Q3UZB0, Q5H9R4, Q5JY77, Q5R4B2, Q5R7U0, Q5R9J3, Q5RDG2, Q5U310, Q5U4C1, Q5XID7, Q6A058, Q6P1M9, Q6PI77, Q7L311, Q8BHS6, Q8BUY8, Q8N2F6, Q920R4, Q96D09, Q9BE11, Q9CX83, Q9D0L7, Q9P291, Q9UH62, Q6PB60, Q71HP2, Q7L4S7, Q66HF0, Q8K3A6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
394672	GRCh37/hg19 Xp22.33-q28(chrX:318707-155224707)x1	Pathogenic

SpliceAI

866 predictions. Top by Δscore:

Variant	Effect	Δscore
X:102736614:GACA:G	donor_gain	0.9900
X:102736618:G:GG	donor_gain	0.9900
X:102721025:G:GT	donor_gain	0.9800
X:102721065:G:GA	donor_gain	0.9800
X:102736617:A:AG	donor_gain	0.9800
X:102721064:T:TA	donor_gain	0.9700
X:102720818:TAAG:T	donor_loss	0.9600
X:102720819:AAGG:A	donor_loss	0.9600
X:102720820:AG:A	donor_loss	0.9600
X:102720821:GG:G	donor_loss	0.9600
X:102720822:G:T	donor_loss	0.9600
X:102720822:GTAG:G	donor_gain	0.9400
X:102746481:A:T	donor_gain	0.9300
X:102727249:A:AG	acceptor_gain	0.9100
X:102736615:A:T	donor_gain	0.9100
X:102720956:GGA:G	acceptor_gain	0.9000
X:102747429:G:GA	donor_gain	0.9000
X:102736603:C:G	donor_gain	0.8900
X:102721039:G:GT	donor_gain	0.8800
X:102721087:TGC:T	donor_gain	0.8800
X:102736444:T:A	acceptor_gain	0.8800
X:102746689:G:GA	donor_gain	0.8600
X:102721087:TGCAG:T	donor_loss	0.8500
X:102721088:GCAGG:G	donor_loss	0.8500
X:102721089:CAGG:C	donor_loss	0.8500
X:102721090:AGGTA:A	donor_loss	0.8500
X:102721091:G:GT	donor_loss	0.8500
X:102721092:G:GG	donor_loss	0.8500
X:102721093:T:A	donor_loss	0.8500
X:102736441:AATT:A	acceptor_gain	0.8500

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000123838 (X:102724803 A>C), RS1000138235 (X:102746610 C>T), RS1000205035 (X:102734583 C>T), RS1000464718 (X:102746023 C>T), RS1000495868 (X:102724346 G>A), RS1000521986 (X:102743036 T>C), RS1000803957 (X:102733989 T>G), RS1000905270 (X:102733473 A>G), RS1000936038 (X:102734034 G>A), RS1001198775 (X:102734455 A>G), RS1001237759 (X:102723130 A>T), RS1001258634 (X:102747177 T>C), RS1001301498 (X:102724111 A>G), RS1001418114 (X:102733968 T>C), RS1001521955 (X:102722634 T>C,G)

Disease associations

OMIM: gene MIM:300921 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment, decreases expression, decreases methylation	6
Cyclosporine	decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
bisphenol A	decreases methylation	1
trichostatin A	decreases expression	1
tris(2-butoxyethyl) phosphate	affects 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, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Cadmium	increases abundance, decreases expression	1
Estradiol	decreases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Tretinoin	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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