GPRASP2

Summary

GPRASP2 (G protein-coupled receptor associated sorting protein 2, HGNC:25169) is a protein-coding gene on chromosome Xq22.1, encoding G-protein coupled receptor-associated sorting protein 2 (Q96D09). May play a role in regulation of a variety of G-protein coupled receptors.

The protein encoded by this gene is a member of a family that regulates the activity of G protein-coupled receptors (GPCRs). The encoded protein has been shown to be capable of interacting with several GPCRs, including the M1 muscarinic acetylcholine receptor and the calcitonin receptor. Several transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 114928 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome (Supportive, GenCC)
• Clinical variants (ClinVar): 5 total
• Phenotypes (HPO): 13
• MANE Select transcript: NM_001004051

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25169
Approved symbol	GPRASP2
Name	G protein-coupled receptor associated sorting protein 2
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	GASP2, FLJ37327
Ensembl gene	ENSG00000158301
Ensembl biotype	protein_coding
OMIM	300969
Entrez	114928

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 26 protein_coding

ENST00000332262, ENST00000483720, ENST00000486814, ENST00000535209, ENST00000543253, ENST00000907057, ENST00000907058, ENST00000907059, ENST00000907060, ENST00000907061, ENST00000907062, ENST00000907063, ENST00000907064, ENST00000907065, ENST00000907066, ENST00000907067, ENST00000907068, ENST00000907069, ENST00000907070, ENST00000919088, ENST00000919089, ENST00000919090, ENST00000919091, ENST00000945086, ENST00000945087, ENST00000945088

RefSeq mRNA: 6 — MANE Select: NM_001004051 NM_001004051, NM_001184874, NM_001184875, NM_001184876, NM_001199818, NM_138437

Canonical transcript exons

ENST00000483720 — 5 exons

Exon	Start	End
ENSE00001322878	102712448	102712552
ENSE00001520517	102713130	102713217
ENSE00001923525	102714537	102717733
ENSE00003550395	102714189	102714266
ENSE00003688670	102713782	102713849

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 99.57.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5893 / max 71.7681, expressed in 632 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196989	1.5893	632
196988	0.8144	333
209761	0.2706	142

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.57	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.44	gold quality
middle temporal gyrus	UBERON:0002771	99.33	gold quality
pons	UBERON:0000988	97.65	gold quality
postcentral gyrus	UBERON:0002581	97.57	gold quality
superior vestibular nucleus	UBERON:0007227	97.50	gold quality
parietal lobe	UBERON:0001872	97.44	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.33	gold quality
entorhinal cortex	UBERON:0002728	97.27	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.26	gold quality
superior frontal gyrus	UBERON:0002661	97.22	gold quality
cerebellar vermis	UBERON:0004720	97.15	gold quality
oviduct epithelium	UBERON:0004804	96.71	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.61	gold quality
left ventricle myocardium	UBERON:0006566	96.04	gold quality
medulla oblongata	UBERON:0001896	95.95	gold quality
substantia nigra pars compacta	UBERON:0001965	95.51	gold quality
germinal epithelium of ovary	UBERON:0001304	95.24	gold quality
ventral tegmental area	UBERON:0002691	94.78	gold quality
epithelial cell of pancreas	CL:0000083	94.69	gold quality
occipital lobe	UBERON:0002021	94.57	gold quality
kidney epithelium	UBERON:0004819	94.51	gold quality
adult organism	UBERON:0007023	94.20	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.11	gold quality
primary visual cortex	UBERON:0002436	93.97	gold quality
caput epididymis	UBERON:0004358	93.59	gold quality
parotid gland	UBERON:0001831	93.42	gold quality
prefrontal cortex	UBERON:0000451	92.66	gold quality
frontal cortex	UBERON:0001870	92.56	gold quality
tibia	UBERON:0000979	92.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting GPRASP2, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-4638-3P	97.90	65.75	905
HSA-MIR-6800-5P	94.59	64.80	525
HSA-MIR-6820-5P	94.04	61.13	161

Literature-anchored findings (GeneRIF, showing 3)

• that huntingtin protein and GASP2 form a complex in cotransfected mammalian cells (PMID:16835690)
• A missense variation of GPRASP2 was first identified to be implicated in X-linked SHL. (PMID:28096187)
• Dynamic expression analysis of armc10, the homologous gene of human GPRASP2, in zebrafish embryos, has been reported. (PMID:28849214)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	armc10	ENSDARG00000062960
mus_musculus	Gprasp2	ENSMUSG00000072966
rattus_norvegicus	Gprasp2	ENSRNOG00000037658
caenorhabditis_elegans		WBGENE00013456

Paralogs (10): ARMCX3 (ENSG00000102401), ARMCX5 (ENSG00000125962), ARMCX1 (ENSG00000126947), ARMC12 (ENSG00000157343), ARMC10 (ENSG00000170632), ARMCX2 (ENSG00000184867), ARMCX4 (ENSG00000196440), GPRASP3 (ENSG00000198908), GPRASP1 (ENSG00000198932), ARMCX6 (ENSG00000198960)

Protein

Protein identifiers

G-protein coupled receptor-associated sorting protein 2 — Q96D09 (reviewed: Q96D09)

All UniProt accessions (1): Q96D09

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in regulation of a variety of G-protein coupled receptors.

Subunit / interactions. Interacts with cytoplasmic tails of a variety of G-protein coupled receptors such as muscarinic acetylcholine receptor M1/CHRM1 and calcitonin receptor/CALCR.

Tissue specificity. Expressed in the brain.

Disease relevance. Deafness, X-linked, 7 (DFNX7) [MIM:301018] A congenital form of bilateral mixed or conductive hearing loss, which is progressive in some patients. Additional clinical features include ear anomalies and facial dysmorphism with bilateral ptosis. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the GPRASP family.

RefSeq proteins (6): NP_001004051, NP_001171803, NP_001171804, NP_001171805, NP_001186747, NP_612446 (=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 (13 total): region of interest 4, compositionally biased region 4, modified residue 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96D09-F1	50.21	0.09

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): 284, 282

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 133 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, TGCGCANK_UNKNOWN, MODULE_418, ATGTTAA_MIR302C, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, TCCAGAT_MIR5165P, TGGNNNNNNKCCAR_UNKNOWN, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOMF_G_PROTEIN_COUPLED_RECEPTOR_BINDING, GCM_CALM1, GOMF_SIGNALING_RECEPTOR_BINDING, ACEVEDO_LIVER_CANCER_UP, CUI_TCF21_TARGETS_2_UP, MODULE_455

GO Biological Process (1): hematopoietic stem cell homeostasis (GO:0061484)

GO Molecular Function (3): amyloid-beta binding (GO:0001540), G protein-coupled receptor binding (GO:0001664), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
homeostasis of number of cells	1
peptide binding	1
signaling receptor binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1619 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPRASP2	CIMAP3	Q8TCI5	805
GPRASP2	SMO	Q99835	607
GPRASP2	DRC4	O95995	489
GPRASP2	BEX1	Q9HBH7	456
GPRASP2	ALMS1	Q8TCU4	438
GPRASP2	BEX3	Q00994	423
GPRASP2	CDH6	P55285	404
GPRASP2	PRR12	Q9ULL5	396
GPRASP2	PRRG2	O14669	387
GPRASP2	RNF14	Q9UBS8	368
GPRASP2	SEC24A	O95486	363
GPRASP2	NEDD1	Q8NHV4	362
GPRASP2	CSN1S1	P47710	353
GPRASP2	NDFIP1	Q9BT67	353
GPRASP2	ATP6AP1	Q15904	353
GPRASP2	SAR1B	Q9Y6B6	353
GPRASP2	NDUFA6	P56556	353

IntAct

204 interactions, top by confidence:

A	B	Type	Score
TCF25	GPRASP2	psi-mi:“MI:0915”(physical association)	0.900
GPRASP2	TCF25	psi-mi:“MI:0915”(physical association)	0.900
CFAP206	GPRASP2	psi-mi:“MI:0915”(physical association)	0.720
CBX8	GPRASP2	psi-mi:“MI:0915”(physical association)	0.720
GPRASP2	CFAP206	psi-mi:“MI:0915”(physical association)	0.720
GPRASP2	CBX8	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GPRASP2	TXN2	psi-mi:“MI:0915”(physical association)	0.670
YWHAG	GPRASP2	psi-mi:“MI:0915”(physical association)	0.670
HTT	GPRASP2	psi-mi:“MI:0915”(physical association)	0.670
TXN2	GPRASP2	psi-mi:“MI:0915”(physical association)	0.670
PRG2	YPEL5	psi-mi:“MI:0914”(association)	0.640
RTL10	GPRASP2	psi-mi:“MI:0915”(physical association)	0.620
GPRASP2	RTL10	psi-mi:“MI:0915”(physical association)	0.620
GPRASP2		psi-mi:“MI:0915”(physical association)	0.560
	GPRASP2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (156): GPRASP2 (Two-hybrid), GPRASP2 (Two-hybrid), LOC149950 (Two-hybrid), C6orf165 (Two-hybrid), GPRASP2 (Affinity Capture-MS), GPRASP2 (Affinity Capture-MS), GPRASP2 (Affinity Capture-MS), C6orf165 (Two-hybrid), GPRASP2 (Two-hybrid), GPRASP2 (Affinity Capture-MS), GPRASP2 (Affinity Capture-MS), GPRASP2 (Affinity Capture-MS), GPRASP2 (Affinity Capture-MS), GPRASP2 (Affinity Capture-MS), GPRASP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YXV3, A0A172M4N0, A2VE23, A5PL33, C7EMF5, E7EW31, F1NSM7, I3L273, O15027, O48582, O55189, O55196, O97939, P0C671, P0DV77, P14138, Q14D33, Q1XI13, Q28989, Q3B7M4, Q4R729, Q5R7U0, Q5SWP3, Q62840, Q63003, Q6E0U4, Q6H236, Q6NUN9, Q6UXA7, Q7Z2K8, Q86UU5, Q8BM15, Q8K4E0, Q8K4L6, Q8N1P7, Q8N3D4, Q96D09, Q96JG9, Q9BGL9, Q9D7G9

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

653 predictions. Top by Δscore:

Variant	Effect	Δscore
X:102713556:G:GT	donor_gain	1.0000
X:102714172:T:G	acceptor_gain	1.0000
X:102714614:G:GT	donor_gain	1.0000
X:102713845:TGGAG:T	donor_loss	0.9900
X:102713850:G:GG	donor_loss	0.9900
X:102714265:AGG:A	donor_loss	0.9900
X:102714266:GGT:G	donor_loss	0.9900
X:102714267:G:GA	donor_loss	0.9900
X:102714535:A:AG	acceptor_gain	0.9900
X:102714536:G:GG	acceptor_gain	0.9900
X:102714615:A:T	donor_gain	0.9900
X:102714177:A:AG	acceptor_gain	0.9800
X:102714185:GTA:G	acceptor_loss	0.9800
X:102714186:TA:T	acceptor_loss	0.9800
X:102714187:A:AG	acceptor_gain	0.9800
X:102714187:A:T	acceptor_loss	0.9800
X:102714188:G:A	acceptor_loss	0.9800
X:102714188:G:GG	acceptor_gain	0.9800
X:102714534:TA:T	acceptor_loss	0.9800
X:102714535:A:AT	acceptor_loss	0.9800
X:102714536:G:A	acceptor_loss	0.9800
X:102713588:G:GT	donor_gain	0.9700
X:102713673:A:G	donor_gain	0.9700
X:102713780:A:AG	acceptor_gain	0.9700
X:102713781:G:GG	acceptor_gain	0.9700
X:102713817:C:T	donor_gain	0.9700
X:102714177:ACTT:A	acceptor_gain	0.9700
X:102713658:A:T	donor_gain	0.9600
X:102713662:TTGA:T	donor_gain	0.9600
X:102713767:T:G	acceptor_gain	0.9600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000512925 (X:102711874 C>A,G,T), RS1002404477 (X:102712379 C>A,G), RS1002453286 (X:102712663 T>C), RS1003053804 (X:102716354 T>C), RS1003294759 (X:102717443 G>A,T), RS1003461020 (X:102714374 C>T), RS1003816427 (X:102714041 A>C), RS1004409131 (X:102713030 G>C), RS1004646035 (X:102710751 A>T), RS1004741042 (X:102711272 T>G), RS1007120178 (X:102715043 T>G), RS1007447200 (X:102713122 T>C), RS1007483791 (X:102717943 A>G), RS1007859978 (X:102717569 C>T), RS1009499180 (X:102713961 G>T)

Disease associations

OMIM: gene MIM:300969 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome	Supportive	X-linked

Mondo (1): X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome (MONDO:0044702)

Orphanet (0):

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000402	Stenosis of the external auditory canal
HP:0000413	Atresia of the external auditory canal
HP:0000431	Wide nasal bridge
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000574	Thick eyebrow
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001419	X-linked recessive inheritance
HP:0003577	Congenital onset
HP:0011480	Unilateral microphthalmos

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

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	3
trichostatin A	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
pirinixic acid	increases activity, affects binding, decreases expression	1
sodium arsenite	increases expression	1
beta-methylcholine	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
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases expression	1
Folic Acid	decreases expression	1
Nickel	decreases expression	1
Vanadates	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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