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). G protein-coupled receptor that plays key roles in the renin-angiotensin system (RAS) specifically in the protective, counter-regulatory arm of the RAS.

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

• GWAS associations: 5
• Clinical variants (ClinVar): 54 total
• GTEx eGene: eQTL in 5 tissues, sQTL in 0 (q < 0.05)
• Drug target: yes — 1 curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.32 (intermediate), LOEUF 1.87 (unconstrained)
• MANE Select transcript: NM_002377
• Notable: 54 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 3 — 3 protein_coding

MANE Select: ENST00000674077

ENST00000674077, ENST00000252660, ENST00001063634

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.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, prefrontal cortex, Brodmann (1909) area 9, frontal cortex, frontal lobe.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MAS1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 5 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

5 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	eqtl	7.4e-03	+0.38	6:159846453:C:T
Artery Tibial	eqtl	1.5e-02	+0.15	6:159932259:C:T
Brain Cortex	eqtl	3.3e-02	-0.74	6:159567899:T:TC
Testis	eqtl	4.2e-02	-0.29	6:159836762:G:C
Brain Anterior cingulate cortex BA24	eqtl	4.8e-02	+0.56	6:160791964:A:G

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 224 tissues 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
brain	UBERON:0000955	42.23	gold quality
skin of hip	UBERON:0001554	42.22	silver quality
vastus lateralis	UBERON:0001379	41.78	gold quality
hindlimb stylopod muscle	UBERON:0004252	41.76	gold quality
quadriceps femoris	UBERON:0001377	41.73	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
ventral tegmental area	UBERON:0002691	40.87	gold quality
pigmented layer of retina	UBERON:0001782	40.82	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality
oviduct epithelium	UBERON:0004804	40.03	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
colonic mucosa	UBERON:0000317	39.84	gold quality
deltoid	UBERON:0001476	39.83	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
parotid gland	UBERON:0001831	39.81	gold quality
oocyte	CL:0000023	39.80	gold quality
urethra	UBERON:0000057	39.80	gold quality
heart right ventricle	UBERON:0002080	39.79	gold quality
pericardium	UBERON:0002407	39.77	gold quality
layer of synovial tissue	UBERON:0007616	39.77	gold quality
endothelial cell	CL:0000115	39.75	gold quality
synovial joint	UBERON:0002217	39.70	gold quality
dorsal root ganglion	UBERON:0000044	39.68	gold quality
nipple	UBERON:0002030	39.68	gold quality
bronchial epithelial cell	CL:0002328	39.65	gold quality
skeletal muscle tissue	UBERON:0001134	39.65	gold quality
decidua	UBERON:0002450	39.65	gold quality
penis	UBERON:0000989	39.64	gold quality
gingiva	UBERON:0001828	39.64	gold quality
bronchus	UBERON:0002185	39.64	gold quality
trigeminal ganglion	UBERON:0001675	39.63	gold quality
tendon of biceps brachii	UBERON:0008188	39.60	gold quality
parietal lobe	UBERON:0001872	39.58	gold quality
inferior vagus X ganglion	UBERON:0005363	39.57	gold quality
superior surface of tongue	UBERON:0007371	39.56	gold quality
pylorus	UBERON:0001166	39.55	gold quality
postcentral gyrus	UBERON:0002581	39.54	gold quality
renal medulla	UBERON:0000362	39.53	gold quality
pons	UBERON:0000988	39.51	gold quality
thymus	UBERON:0002370	39.50	gold quality
upper leg skin	UBERON:0004262	39.49	silver quality
medulla oblongata	UBERON:0001896	39.48	gold quality
superior vestibular nucleus	UBERON:0007227	39.47	gold quality
cardia of stomach	UBERON:0001162	39.46	gold quality
parietal pleura	UBERON:0002400	39.45	gold quality
monocyte	CL:0000576	39.40	gold quality
Brodmann (1909) area 23	UBERON:0013554	39.40	gold quality
dorsal plus ventral thalamus	UBERON:0001897	39.38	gold quality
tongue	UBERON:0001723	39.37	gold quality
cerebellar vermis	UBERON:0004720	39.37	gold quality
oral cavity	UBERON:0000167	39.35	gold quality
subthalamic nucleus	UBERON:0001906	39.35	gold quality
trachea	UBERON:0003126	39.33	gold quality
vena cava	UBERON:0004087	39.31	gold quality
pharyngeal mucosa	UBERON:0000355	39.27	gold quality
entorhinal cortex	UBERON:0002728	39.25	gold quality
substantia nigra pars compacta	UBERON:0001965	39.23	gold quality
visceral pleura	UBERON:0002401	39.23	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

HPA expression

RNA tissue specificity: Tissue enriched

46 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	32.4
Hippocampal formation	tissue	25.7
Hippocampus	tissue	14.8	not detected
Caudate putamen	tissue	13.7
Cerebral cortex	tissue	12.8	low
Temporal cortex	tissue	12.8
Somatosensory cortex	tissue	11.9
Entorhinal cortex	tissue	10.4
Occipital cortex	tissue	10.4
Amygdala	tissue	7.9
Retrosplenial and cingulate cortex	tissue	7.7
Prefrontal cortex	tissue	6.8
Insular cortex	tissue	6.7
Postcentral gyrus	tissue	5.0
Motor cortex	tissue	4.9
Retrosplenial cortex	tissue	4.9
Olfactory bulb	tissue	2.0
Choroid plexus	tissue	1.6
Nucleus accumbens	tissue	0.9
Locus coeruleus	tissue	0.8
Substantia nigra	tissue	0.7
Cervix	tissue	0.4	not detected
Ventral forebrain	tissue	0.4
Seminal vesicle	tissue	0.3	not detected
Corpus callosum	tissue	0.3
Septum	tissue	0.3
Lymph node	tissue	0.2	not detected
Vagina	tissue	0.2	not detected
Epididymis	tissue	0.2	not detected
Superior colliculi	tissue	0.2
Bone marrow	tissue	0.2	not detected
Retina	tissue	0.1
Pons	tissue	0.1
Salivary gland	tissue	0.1	not detected
Skeletal muscle	tissue	0.1	not detected
Endometrium 1	tissue	0.1	not detected
Basal ganglia	tissue	0.1	not detected
Midbrain	tissue	0.1
Medulla oblongata	tissue	0.1
Thalamus	tissue	0.1
Hypothalamus	tissue	0.1
Spinal cord	tissue	0.1
Fallopian tube	tissue	0.1	not detected
Smooth muscle	tissue	0.0	low
Colon	tissue	0.0	low
Kidney	tissue	0.0	low

Brain sub-regions (HPA Brain Atlas): detected in 287; highest nTPM — Blood vessel (35.5), Dorsal spinal cord (31.1), Dorsal hippocampus (30.2), Dorsal hippocampus (25.7), Hippocampus, CA1 (23.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting MAS1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

9 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.318, LOEUF 1.87, missense Z 0.764 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000674077 — one region, missense o/e 0.94.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96918) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 18 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased anxiety-related response	1
short tibia	1
abnormal renal glomerular capsule morphology	1
albuminuria	1
increased urine microalbumin level	1
enhanced long-term potentiation	1
renal interstitial fibrosis	1
abnormal bone structure	1
abnormal renal glomerulus morphology	1
decreased renal plasma flow rate	1
increased renal glomerular filtration rate	1
increased renal vascular resistance	1
increased creatinine clearance	1
decreased urine sodium level	1
increased urine osmolality	1
increased bone mineral content	1
renal glomerulus fibrosis	1
decreased urine flow rate	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gorilla gorilla gorilla	Q4QXU0	97.6%	Diamond
Rhinopithecus bieti	Q4QXU2	97.6%	Diamond
Trachypithecus francoisi	Q4QXU4	97.6%	Diamond
Pan troglodytes	Q4QXX9	97.6%	Diamond
Macaca mulatta	Q4QXU5	97.0%	Diamond
Macaca fascicularis	Q5U9D9	97.0%	Diamond
Pongo pygmaeus	Q4QXU3	96.4%	Diamond
Hoolock hoolock	Q4QXU6	92.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PNLDC1	protein-coding	154197
IGF2R	protein-coding	3482
AIRN	ncRNA	100271873
MRPL18	protein-coding	29074
SNORA20	snoRNA	677806
SNORA29	snoRNA	677812
TCP1	protein-coding	6950
SLC22A1	protein-coding	6580

Protein

Protein identifiers

Proto-oncogene Mas — P04201 (reviewed: P04201)

All UniProt accessions (2): P04201, W8W3P4

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor that plays key roles in the renin-angiotensin system (RAS) specifically in the protective, counter-regulatory arm of the RAS. Receptor mainly stimulated by angiotensin 1-7, which is a bioactive metabolite of the angiotensin produced by ACE2. Activation promotes nitric oxide via PI3K/Akt-eNOS pathway. Modulates also the MAPK, ERK1/2, and NF-kappa-B signaling. 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. Acts as functional receptor for CXCL17 and induces chemotactic movement.

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 by resolution:

PDB	Title	Method	Resolution (Å)
9X3Z	NPFF bound Mas1 Receptor Complex	ELECTRON MICROSCOPY	2.54
9X3Y	NPFF bound Mas1 Receptor	ELECTRON MICROSCOPY	2.77
9JLC	Cryo-EM structure of MAS1-Gi Complex with AVE 0991	ELECTRON MICROSCOPY	2.98
25IK	Cryo-EM structure of MasR(FL)-Gq	ELECTRON MICROSCOPY	3
9X40	AR234958 bound Mas1 Receptor Complex	ELECTRON MICROSCOPY	3.07
25IL	Cryo-EM structure of MasR(del2-25)-Gq	ELECTRON MICROSCOPY	3.2
9X41	AR234958 bound Mas1 Receptor	ELECTRON MICROSCOPY	3.31

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: G-protein coupled receptors, GPCRs excl olfactory receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, Disease related genes, Potential drug targets

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

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)

Type	Positions
Disulfide bond	171–184

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	5, 16, 22

Mutagenesis-validated functional residues (1)

Position	Phenotype
138	fails to activate gna11.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-375276	Peptide ligand-binding receptors	electronic
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

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), cell migration (GO:0016477), chemokine-mediated signaling pathway (GO:0070098), 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), C-C chemokine receptor activity (GO:0016493), peptide binding (GO:0042277), protein binding (GO:0005515)

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

Reactome top-level categories

4 top-level categories:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
Signal Transduction	1
GPCR ligand binding	1
Signaling by GPCR	1

GO top-level categories

28 GO namespaces:

Category	Terms
G protein-coupled receptor signaling pathway	3
angiotensin-activated 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
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
cell motility	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	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
chemokine receptor activity	1
C-C chemokine binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 16 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
cell migration	BP	direct assay
chemokine-mediated signaling pathway	BP	direct assay
phospholipase C-activating angiotensin-activated signaling pathway	BP	mutant phenotype
plasma membrane	CC	direct assay
C-C chemokine receptor activity	MF	direct assay
G protein-coupled receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 930 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAS1	NPFF	O15130	954
MAS1	ACE2	Q9BYF1	668
MAS1	SMUG1	Q53HV7	661
MAS1	IGF2R	P11717	642
MAS1	TACR2	P21452	601
MAS1	ACE	P12821	562
MAS1	ZNF428	Q96B54	555
MAS1	REN	P00797	553
MAS1	AGT	P01019	550
MAS1	UBL7	Q96S82	538
MAS1	UNG	P13051	510
MAS1	SLC44A3	Q8N4M1	477
MAS1	CIAPIN1	Q6FI81	464
MAS1	POLB	P06746	460
MAS1	ATP6AP2	O75787	437

IntAct

Human interaction partners of MAS1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 75 partners by confidence:

Partner	Interaction type	MIscore	Records
DLG1	direct interaction	0.590	3
CASK	association	0.590	2
POTEF	association	0.530	2
PATJ	direct interaction	0.440	8
GRIP2	direct interaction	0.440	4
DLG4	direct interaction	0.440	3
GRIP1	direct interaction	0.440	3
MAGI2	direct interaction	0.440	3
NHERF4	direct interaction	0.440	3
WHRN	direct interaction	0.440	3
APBA1	direct interaction	0.440	2
APBA2	direct interaction	0.440	2
DLG2	direct interaction	0.440	2
DLG3	direct interaction	0.440	2
FRMPD2	direct interaction	0.440	2
GRID2IP	direct interaction	0.440	2
IL16	direct interaction	0.440	2
LNX1	direct interaction	0.440	2
LNX2	direct interaction	0.440	2
MAGI1	direct interaction	0.440	2
SCRIB	direct interaction	0.440	2
TJP1	direct interaction	0.440	2
AHNAK	direct interaction	0.440	1
APBA3	direct interaction	0.440	1
ARHGAP21	direct interaction	0.440	1
ARHGEF11	direct interaction	0.440	1
ARHGEF12	direct interaction	0.440	1
CARD11	direct interaction	0.440	1
DLG5	direct interaction	0.440	1
DVL3	direct interaction	0.440	1

BioGRID (132 interactions; top human partners by supporting records): ABCD1 (Affinity Capture-MS; 2 records), ABHD17B (Affinity Capture-MS; 2 records), ABHD3 (Affinity Capture-MS; 2 records), ACAD10 (Affinity Capture-MS; 2 records), ACTA2 (Affinity Capture-MS; 2 records), ARL10 (Affinity Capture-MS; 2 records), ARRB2 (Affinity Capture-MS; 2 records), ATAD1 (Affinity Capture-MS; 2 records), ATL2 (Affinity Capture-MS; 2 records), ATL3 (Affinity Capture-MS; 2 records), ATP13A3 (Affinity Capture-MS; 2 records), ATP6V1H (Affinity Capture-MS; 2 records), BMPR1A (Affinity Capture-MS; 2 records), BTAF1 (Affinity Capture-MS; 2 records), CRYAB (Affinity Capture-MS; 2 records)

SIGNOR signaling

4 signaling 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

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
★ AGTR1-MAS1 complex	2	MAS1, AGTR1
AGTR2-MAS1 complex	2	AGTR2, MAS1
★ BDKRB2-MAS1 receptor	2	BDKRB2, MAS1

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

Genetic variants

Variant evidence for MAS1: 54 ClinVar records (0 pathogenic / likely pathogenic); 5 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 281):

Position(s)	Effect	Δscore	Sites
6:159906905–159906906	acceptor_gain	0.9900	2
6:159891134–159891135	donor_loss	0.9800	6
6:159891138	donor_loss	0.9800	3
6:159906911	acceptor_gain	0.9800
6:159891137	donor_loss	0.9700
6:159907945	donor_gain	0.9700
6:159906913	acceptor_gain	0.9600
6:159906918–159906919	acceptor_loss	0.9500	6
6:159899323	donor_gain	0.9300
6:159906900	acceptor_gain	0.9300

HPA cancer prognostics

RNA cancer specificity: Not detected

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	8.51e-05

Disease associations

OMIM: gene MIM:165180 | disease phenotypes:

GWAS associations

5 associations:

Study	Trait	p-value
GCST003127_12	Lipoprotein (a) levels	5e-11
GCST005952_6	Body mass index (age>50)	2e-8
GCST005950_13	Body mass index x sex x age interaction (4df test)	3e-7
GCST005951_64	Body mass index	4e-6
GCST009391_364	Metabolite levels	8e-6

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0006925	lipoprotein A measurement
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0010385	phosphatidylcholine 38:3 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3559701 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the MAS1 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
TALFIRASTIDE	Protein	2

PharmGKB: 1 entry (CPIC guideline: no)

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

Binding affinities (BindingDB)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4578721	IC50	0.3 nM
CHEMBL4303593	IC50	21 nM

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	increases expression, affects cotreatment	1
Lipopolysaccharides	affects cotreatment, increases expression, affects response to substance	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

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_F5BG	EDITGENE MAS1 Knockout A549 Cell Line	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MAS1 across ~30M SureChEMBL compounds — explore on Sugi Predict.