MAS1

Summary

MAS1 (MAS1 proto-oncogene, G protein-coupled receptor, HGNC:6899) is a protein-coding gene on chromosome 6q25.3, encoding Proto-oncogene Mas (P04201). Receptor for angiotensin 1-7.

This gene encodes a class I seven-transmembrane G-protein-coupled receptor. The encoded protein is a receptor for angiotensin-(1-7) and preferentially couples to the Gq protein, activating the phospholipase C signaling pathway. The encoded protein may play a role in multiple processes including hypotension, smooth muscle relaxation and cardioprotection by mediating the effects of angiotensin-(1-7).

Source: NCBI Gene 4142 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 54 total
• Druggable target: yes
• MANE Select transcript: NM_002377

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6899
Approved symbol	MAS1
Name	MAS1 proto-oncogene, G protein-coupled receptor
Location	6q25.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000130368
Ensembl biotype	protein_coding
OMIM	165180
Entrez	4142

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000252660, ENST00000674077

RefSeq mRNA: 2 — MANE Select: NM_002377 NM_001366704, NM_002377

CCDS: CCDS5272

Canonical transcript exons

ENST00000674077 — 3 exons

Exon	Start	End
ENSE00003896828	159890988	159891133
ENSE00003896993	159899186	159899392
ENSE00003897123	159906920	159917447

Expression profiles

Bgee: expression breadth broad, 39 present calls, max score 71.04.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3778 / max 47.3164, expressed in 44 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71001	0.3271	41
71000	0.0506	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	71.04	silver quality
prefrontal cortex	UBERON:0000451	65.19	gold quality
Brodmann (1909) area 9	UBERON:0013540	58.63	gold quality
frontal cortex	UBERON:0001870	58.27	gold quality
right frontal lobe	UBERON:0002810	57.03	gold quality
neocortex	UBERON:0001950	56.91	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	55.80	gold quality
anterior cingulate cortex	UBERON:0009835	54.64	gold quality
cerebral cortex	UBERON:0000956	54.59	gold quality
primary visual cortex	UBERON:0002436	53.27	gold quality
Ammon’s horn	UBERON:0001954	53.17	gold quality
occipital lobe	UBERON:0002021	49.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	49.02	gold quality
germinal epithelium of ovary	UBERON:0001304	47.80	gold quality
stromal cell of endometrium	CL:0002255	47.76	gold quality
amygdala	UBERON:0001876	47.50	gold quality
lymph node	UBERON:0000029	46.77	gold quality
sural nerve	UBERON:0015488	46.47	gold quality
ectocervix	UBERON:0012249	46.38	gold quality
uterine cervix	UBERON:0000002	46.07	gold quality
bone marrow cell	CL:0002092	45.67	gold quality
endocervix	UBERON:0000458	45.58	gold quality
temporal lobe	UBERON:0001871	44.30	gold quality
superior frontal gyrus	UBERON:0002661	44.25	gold quality
forebrain	UBERON:0001890	43.97	gold quality
smooth muscle tissue	UBERON:0001135	43.46	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
gall bladder	UBERON:0002110	43.07	gold quality
bone marrow	UBERON:0002371	42.61	gold quality
secondary oocyte	CL:0000655	42.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting MAS1, 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-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-6728-5P	97.79	66.33	891
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-6888-5P	95.89	63.78	831

Literature-anchored findings (GeneRIF, showing 40)

• the ability of MAS to up-regulate AT(1) receptor levels reflects the constitutive capacity of MAS to activate Galpha(q)/Galpha(11) and hence stimulate PKC-dependent phosphorylation of the AT(1) receptor (PMID:16611642)
• Mas, MrgD, and MRG mediated Ang IV-stimulated AA release that was highest for Mas. While Ang III activated Mas and MrgX2, Ang II stimulated AA release via Mas and MRG. (PMID:18636314)
• The vasoactive peptide angiotensin-(1-7), its receptor Mas and the angiotensin-converting enzyme type 2 are expressed in the human endometrium. (PMID:19164480)
• the Mas oncogene acts as a receptor for Angiotensin (1-7)–REVIEW (PMID:19461648)
• The immunolocalization of Ang-(1-7) and its receptor Mas in testes of fertile and infertile men suggests that this system may be altered when spermatogenesis is severely impaired. (PMID:20361351)
• Angiotensin-(1-7), its receptor Mas, and ACE2 are expressed in the human ovary (PMID:20674894)
• Report expression (pro)renin receptors and angiotensin converting enzyme 2/angiotensin-(1-7)/Mas receptor axis in human aortic valve stenosis. (PMID:21316680)
• Activation of Mas during myocardial infarction contributes to ischemia-reperfusion injury and suggest that inhibition of Mas-G(q) signaling may provide a new therapeutic strategy directed at cardioprotection. (PMID:22003054)
• MasR was significantly upregulated in colon adenocarcinoma compared with non-neoplastic colon mucosa, which showed little or no expression of it. ACE gene expression and enzymatic activity were also increased in the tumors. (PMID:22048948)
• Mas appears to be a critical component required for NO-mediated vasodilatation induced by renin angiotensin system-dependent and RAS-independent agonists and therefore arises as a key pharmacological target to modulate endothelial function (PMID:23459756)
• Data suggest that angiotensin converting enzyme 2/angiotensin II-(1-7)/MAS1 axis regulates leukocyte recruitment/activation, cell proliferation, and inflammation/fibrosis; main topic here is kidney/inflammatory renal disease. [REVIEW] (PMID:23488800)
• Control of adipogenesis by the autocrine interplays between angiotensin 1-7/Mas receptor and angiotensin II/AT1 receptor signaling pathways. (PMID:23592774)
• A proximal promoter construct for the MAS gene was repressed by the SOX [SRY (sex-determining region on the Y chromosome) box] proteins SRY, SOX2, SOX3 and SOX14, of which SRY is known to interact with the KRAB domain. (PMID:24128372)
• Up-regulation of the ACE2/Ang-(1-7)/Mas axis protected against pulmonary fibrosis by inhibiting the MAPK/NF-kappaB pathway. (PMID:24168260)
• Data show that MAS receptor exhibited constitutive activity that was inhibited by the non-peptide inverse agonist. (PMID:25068582)
• MAS1 might act as an inhibitory regulator of breast cancer. (PMID:26080617)
• Ang-(1-7) downregulated AT1R mRNA, upregulated mRNA levels of Ang II type 2 receptor (AT2R) and Mas receptor (MasR) and p38-MAPK phosphorylation and suppressed H22 cell-endothelial cell communication (PMID:26225830)
• These results indicated that angiotensin-(1-7)/ACE2/Mas axis may reduce liver lipid accumulation partly by regulating lipid-metabolizing genes through ATP/P2 receptor/CaM signaling pathway. (PMID:26883384)
• Here, we review the role and effects of ACE2, ACE2 activators, Ang-(1-7) and synthetic Mas receptor agonists in the control of inflammation and fibrosis in cardiovascular and renal diseases and as counter-regulators of the ACE-Ang II-AT1 axis. (PMID:26995300)
• Downregulation of ACE2/Ang-(1-7)/Mas axis stimulates breast cancer metastasis through the activation of store-operated calcium entry and PAK1/NF-kappaB/Snail1 pathways. (PMID:27063099)
• High levels of MAS is associated with angiogenesis in bladder cancer. (PMID:28599664)
• These findings suggest that mitochondrial assembly receptor signaling may be a promising novel target for oral tongue squamous cell carcinoma. (PMID:28747140)
• These findings suggest a critical role for MasR in cardiomyocyte survival. (PMID:29052864)
• ANG-(1-7) acts on the receptor MAS to influence a range of mechanisms in the heart, kidney, brain, and other tissues. [review] (PMID:29351514)
• High MAS1 expression in the endometrium might promote the initiation of endometriosis via migration of proliferative tissue. (PMID:29982252)
• We have hypothesized the mechanism that reverses the downregulation of the ACE2-angiotensin 1-7/Mas receptor axis path and the upregulation of angiotensin receptor type 1-mediated signaling. Thus, we posit that ACE2, Ang-(1-7), and the Mas receptor could be novel therapeutic targets for treating benign prostatic hyperplasia . (PMID:30055537)
• MAS1 expression in the left atrium in mitral regurgitation patients significantly differed from those in aortic valve disease patients and normal controls. (PMID:30581499)
• The production of ANG 1-7 was significantly lower in breast cancer cells, whereas the expression of MAS receptor was higher than that in the control breast tissue cells. This finding suggests that substances with MAS receptor agonist activity could be useful in the treatment of breast cancer. (PMID:31642813)
• Ang-(1-7) stimulates beige markers and thermogenesis via the Mas receptor. (PMID:31843339)
• Angiotensin- and angiotensin-(1-7) imbalance affects comorbidity of depression and coronary heart disease. (PMID:32599080)
• Oestrogen-mediated upregulation of the Mas receptor contributes to sex differences in acute lung injury and lung vascular barrier regulation. (PMID:32764118)
• Impact of angiotensin II type 1 and G-protein-coupled Mas receptor expression on the pulmonary performance of patients with idiopathic pulmonary fibrosis. (PMID:32777324)
• Localization of angiotensin-(1-7) and Mas receptor in the rat ovary throughout the estrous cycle. (PMID:32875393)
• ACE2/Ang-(1-7)/Mas1 axis and the vascular system: vasoprotection to COVID-19-associated vascular disease. (PMID:33511992)
• Human placenta mesenchymal stem cell protection in ischemic stroke is angiotensin converting enzyme-2 and masR receptor-dependent. (PMID:34124808)
• Neuroinflammation and COVID-19 Ischemic Stroke Recovery-Evolving Evidence for the Mediating Roles of the ACE2/Angiotensin-(1-7)/Mas Receptor Axis and NLRP3 Inflammasome. (PMID:35328506)
• The function of the ACE2/Ang(1-7)/Mas receptor axis of the renin-angiotensin system in myocardial ischemia reperfusion injury. (PMID:35363333)
• Sex Difference in MasR Expression and Functions in the Renal System. (PMID:36148474)
• Mas receptor endocytosis and signaling in health and disease. (PMID:36631200)
• Regulation of vascular angiotensin II type 1 and type 2 receptor and angiotensin-(1-7)/MasR signaling in normal and hypertensive pregnancy. (PMID:38061417)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mas1	ENSMUSG00000068037
rattus_norvegicus	Mas1	ENSRNOG00000014971

Paralogs (10): MRGPRX1 (ENSG00000170255), MRGPRF (ENSG00000172935), MRGPRD (ENSG00000172938), GPR152 (ENSG00000175514), MRGPRX4 (ENSG00000179817), MRGPRX3 (ENSG00000179826), MRGPRG (ENSG00000182170), MRGPRX2 (ENSG00000183695), MRGPRE (ENSG00000184350), MAS1L (ENSG00000204687)

Protein

Protein identifiers

Proto-oncogene Mas — P04201 (reviewed: P04201)

All UniProt accessions (2): P04201, W8W3P4

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for angiotensin 1-7. Acts specifically as a functional antagonist of AGTR1 (angiotensin-2 type 1 receptor), although it up-regulates AGTR1 receptor levels. Positive regulation of AGTR1 levels occurs through activation of the G-proteins GNA11 and GNAQ, and stimulation of the protein kinase C signaling cascade. The antagonist effect on AGTR1 function is probably due to AGTR1 being physically altered by MAS1.

Subunit / interactions. Interacts with AGTR1. Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA.

Subcellular location. Cell membrane.

Miscellaneous. The MAS oncogene has a weak focus-inducing activity in transfected NIH 3T3 cells.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (2): NP_001353633, NP_002368* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000820	Proto-oncogene_Mas	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR026234	MRGPCRFAMILY	Family

Pfam: PF00001

UniProt features (21 total): topological domain 8, transmembrane region 7, glycosylation site 3, chain 1, disulfide bond 1, mutagenesis site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
9X3Z	ELECTRON MICROSCOPY	2.54
9X3Y	ELECTRON MICROSCOPY	2.77
9JLC	ELECTRON MICROSCOPY	2.98
25IK	ELECTRON MICROSCOPY	3
9X40	ELECTRON MICROSCOPY	3.07
25IL	ELECTRON MICROSCOPY	3.2
9X41	ELECTRON MICROSCOPY	3.31

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04201-F1	83.74	0.58

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (1): 171–184

Glycosylation sites (3): 5, 16, 22

Mutagenesis-validated functional residues (1):

Position	Phenotype
138	fails to activate gna11.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors

MSigDB gene sets: 103 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_RESPONSE_TO_ANGIOTENSIN, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, chr6q25, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS

GO Biological Process (8): angiotensin-mediated vasodilation involved in regulation of systemic arterial blood pressure (GO:0002033), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), regulation of inflammatory response (GO:0050727), phospholipase C-activating angiotensin-activated signaling pathway (GO:0086097), signal transduction (GO:0007165), angiotensin-activated signaling pathway (GO:0038166)

GO Molecular Function (6): angiotensin receptor activity (GO:0001595), G protein-coupled receptor activity (GO:0004930), angiotensin type II receptor activity (GO:0004945), peptide binding (GO:0042277), protein binding (GO:0005515), G protein-coupled peptide receptor activity (GO:0008528)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	2
angiotensin-activated signaling pathway	2
G protein-coupled receptor signaling pathway	2
binding	2
maintenance of blood vessel diameter homeostasis by renin-angiotensin	1
negative regulation of systemic arterial blood pressure	1
vasodilation	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cellular response to angiotensin	1
G protein-coupled peptide receptor activity	1
transmembrane signaling receptor activity	1
angiotensin receptor activity	1
peptide receptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

586 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAS1	NPFF	O15130	961
MAS1	AGT	P01019	710
MAS1	ZNF428	Q96B54	691
MAS1	ACE2	Q9BYF1	663
MAS1	SMUG1	Q53HV7	650
MAS1	IGF2R	P11717	643
MAS1	SLC44A3	Q8N4M1	642
MAS1	CIAPIN1	Q6FI81	632
MAS1	UBL7	Q96S82	624
MAS1	REN	P00797	589
MAS1	TACR2	P21452	586
MAS1	ACE	P12821	563
MAS1	AGTR1	P30556	514
MAS1	ADRB1	P08588	498
MAS1	UNG	P13051	497

IntAct

115 interactions, top by confidence:

A	B	Type	Score
MAS1	CASK	psi-mi:“MI:0914”(association)	0.590
MAS1	DLG1	psi-mi:“MI:0407”(direct interaction)	0.590
MAS1	CASK	psi-mi:“MI:0407”(direct interaction)	0.590
DLG1	MAS1	psi-mi:“MI:0407”(direct interaction)	0.590
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
MAS1	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
DLG4	MAS1	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI2	MAS1	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	SNTG2	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	AHNAK	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	APBA1	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGAP21	MAS1	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF11	MAS1	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	CARD11	psi-mi:“MI:0407”(direct interaction)	0.440
MAS1	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (132): MAS1 (Affinity Capture-MS), GPR50 (Affinity Capture-MS), DUSP14 (Affinity Capture-MS), EFHD1 (Affinity Capture-MS), ABCD1 (Affinity Capture-MS), SPG7 (Affinity Capture-MS), RELT (Affinity Capture-MS), SELENBP1 (Affinity Capture-MS), SLC35G2 (Affinity Capture-MS), PKP3 (Affinity Capture-MS), ZYX (Affinity Capture-MS), TMEM11 (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ACAD10 (Affinity Capture-MS), POTEF (Affinity Capture-MS)

ESM2 similar proteins: P04201, P12526, P23749, P30554, P35410, P59534, P59535, Q3KNA1, Q3UG50, Q3UG61, Q4VHE7, Q645S5, Q645U4, Q645Y7, Q645Y8, Q645Y9, Q646A9, Q646B0, Q646C8, Q646D3, Q646F0, Q646F1, Q67ER9, Q67ES7, Q67ET0, Q67ET2, Q7TN38, Q7TN41, Q7TN44, Q7TN51, Q7TQA5, Q7TQA6, Q7TQB8, Q8CIP3, Q8R4G1, Q8TDS7, Q8VCJ6, Q91WW2, Q91WW3, Q91ZB8

Diamond homologs: B9VR26, O55197, O88680, P04201, P12526, P23749, P30554, P35410, Q16581, Q2LL16, Q3KNA1, Q3UG50, Q3UG61, Q4QXU0, Q4QXU2, Q4QXU3, Q4QXU4, Q4QXU5, Q4QXU6, Q4QXX9, Q5REI5, Q5U9D9, Q6L786, Q6TAC8, Q6XKD3, Q7TN38, Q7TN39, Q7TN40, Q7TN41, Q7TN44, Q7TN45, Q7TN49, Q7TN50, Q7TN51, Q86SM5, Q8CIP3, Q8NGA4, Q8R4G1, Q8TDS7, Q8VCJ6

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MAS1	down-regulates	Inflammation
“Angiotensin 1-7”	“up-regulates activity”	MAS1	binding
MAS1	“down-regulates activity”	AGTR1	binding
MAS1	“up-regulates activity”	FLNA	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	54.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	52.3×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	52.3×	1e-06
Long-term potentiation	5	45.8×	2e-06
Assembly and cell surface presentation of NMDA receptors	9	43.9×	3e-11
Neurexins and neuroligins	10	37.9×	1e-11
Protein-protein interactions at synapses	6	30.6×	1e-06
RHOA GTPase cycle	5	7.2×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	80.7×	1e-14
protein localization to synapse	6	63.8×	6e-08
receptor clustering	7	60.7×	4e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	6	41.3×	6e-07
bicellular tight junction assembly	5	22.9×	1e-04
cell-cell adhesion	9	12.7×	2e-06
protein-containing complex assembly	8	12.7×	1e-05
protein localization to plasma membrane	7	10.6×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

312 predictions. Top by Δscore:

Variant	Effect	Δscore
6:159907945:G:GT	donor_gain	0.9900
6:159907945:G:T	donor_gain	0.9900
6:159908714:TTGTG:T	donor_gain	0.9800
6:159907917:T:G	donor_gain	0.9500
6:159907934:GAACT:G	donor_gain	0.9400
6:159908794:A:T	donor_gain	0.9400
6:159907905:A:AG	donor_gain	0.9300
6:159908715:T:TA	donor_gain	0.9100
6:159908005:T:G	donor_gain	0.8900
6:159908742:AGAGG:A	donor_gain	0.8900
6:159906754:TCCTA:T	donor_gain	0.8800
6:159907977:C:A	donor_gain	0.8700
6:159907600:G:GT	donor_gain	0.8400
6:159912308:T:G	donor_gain	0.7900
6:159907812:G:GG	donor_gain	0.7800
6:159907911:TCA:T	donor_gain	0.7800
6:159907912:CAC:C	donor_gain	0.7800
6:159907913:ACA:A	donor_gain	0.7800
6:159907979:T:G	donor_gain	0.7800
6:159907608:C:G	donor_gain	0.7700
6:159907811:A:AG	donor_gain	0.7700
6:159907831:G:GT	donor_gain	0.7700
6:159907978:A:AG	donor_gain	0.7700
6:159907710:A:AG	donor_gain	0.7600
6:159907710:A:G	donor_gain	0.7600
6:159907774:T:TA	donor_gain	0.7600
6:159907775:A:AA	donor_gain	0.7600
6:159907809:GCA:G	donor_gain	0.7600
6:159908002:GACT:G	donor_gain	0.7600
6:159908197:G:GT	donor_gain	0.7600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000019821 (6:159914205 C>G), RS1000176833 (6:159906777 T>A,G), RS1000338127 (6:159901519 G>A), RS1000347338 (6:159886857 A>C), RS1000378482 (6:159887267 C>A,T), RS1000404189 (6:159894734 A>G), RS1000515904 (6:159905733 T>A,C), RS1000540214 (6:159892560 G>T), RS1000656036 (6:159905998 C>G,T), RS1000763489 (6:159898535 C>G,T), RS1000813312 (6:159900300 C>T), RS1000876187 (6:159917086 C>T), RS1000876959 (6:159901666 A>G), RS1000911575 (6:159892306 T>C), RS1001035225 (6:159910850 T>C,G)

Disease associations

OMIM: gene MIM:165180 | 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: yes

ChEMBL targets (1): CHEMBL3559701 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Mas1, BB₃/Brs3, GPR17

Most potent curated ligand interactions (13 total), top 13:

Ligand	Action	Affinity	Parameter
[125I]angiotensin-(1-7) (human, mouse, rat)	Full agonist	9.08	pKd
[D-Ala7]-angiotensin(1-7)	Antagonist	8.3	pKi
AR291903	Inverse agonist	8.0	pEC50
AVE 0991	Full agonist	7.32	pIC50
angiotensin-(1-7)	Agonist	7.31	pKi
AR234958	Agonist	7.02	pEC50
AR305352	Inverse agonist	6.78	pIC50
AR244555	Inverse agonist	6.73	pIC50
AR234960	Full agonist	6.46	pEC50
neuropeptide FF	Full agonist	6.4	pEC50
CGEN-856	Full agonist	6.24	pEC50
CGEN-857	Full agonist	6.0	pEC50
MBP7	Full agonist	4.44	pEC50

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	IC50	0.3	nM	CHEMBL4578721
7.68	IC50	21	nM	CHEMBL4303593

PubChem BioAssay actives

2 with measured affinity, of 2 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(1R)-1-carboxyethyl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	1560684: Antagonist activity at N-terminal c-Myc tagged human MasR expressed in HEK293T cells by cAMP accumulation based assay	ic50	0.0003	uM
1-ethyl-3-[3-[4-[(5-formyl-4-methoxy-2-phenylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylurea	1560683: Agonist activity at N-terminal c-Myc tagged human MasR expressed in HEK293T cells assessed as reduction in forskolin-induced cAMP accumulation	ic50	0.0210	uM

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
incobotulinumtoxinA	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Hydralazine	affects cotreatment, increases expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Valproic Acid	affects cotreatment, increases expression	1
Cyclosporine	increases methylation	1
Cadmium Chloride	increases expression	1
tert-Butylhydroperoxide	decreases methylation	1

ChEMBL screening assays

4 unique, capped per target: 2 functional, 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4358375	Functional	Agonist activity at N-terminal c-Myc tagged human MasR expressed in HEK293T cells assessed as reduction in forskolin-induced cAMP accumulation	The Other Angiotensin II Receptor: AT2R as a Therapeutic Target. — J Med Chem
CHEMBL4883521	Binding	PRESTO-Tango GPCRome screening (MAS1)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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