MSR1

Summary

MSR1 (macrophage scavenger receptor 1, HGNC:7376) is a protein-coding gene on chromosome 8p22, encoding Macrophage scavenger receptor types I and II (P21757). Membrane glycoproteins implicated in the pathologic deposition of cholesterol in arterial walls during atherogenesis.

This gene encodes the class A macrophage scavenger receptors, which include three different types (1, 2, 3) generated by alternative splicing of this gene. These receptors or isoforms are macrophage-specific trimeric integral membrane glycoproteins and have been implicated in many macrophage-associated physiological and pathological processes including atherosclerosis, Alzheimer’s disease, and host defense. The isoforms type 1 and type 2 are functional receptors and are able to mediate the endocytosis of modified low density lipoproteins (LDLs). The isoform type 3 does not internalize modified LDL (acetyl-LDL) despite having the domain shown to mediate this function in the types 1 and 2 isoforms. It has an altered intracellular processing and is trapped within the endoplasmic reticulum, making it unable to perform endocytosis. The isoform type 3 can inhibit the function of isoforms type 1 and type 2 when co-expressed, indicating a dominant negative effect and suggesting a mechanism for regulation of scavenger receptor activity in macrophages.

Source: NCBI Gene 4481 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Barrett esophagus (Limited, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 145 total — 2 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes
• MANE Select transcript: NM_138715

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7376
Approved symbol	MSR1
Name	macrophage scavenger receptor 1
Location	8p22
Locus type	gene with protein product
Status	Approved
Aliases	SCARA1, CD204, SR-AI, SR-AII, SR-AIII, SR-A
Ensembl gene	ENSG00000038945
Ensembl biotype	protein_coding
OMIM	153622
Entrez	4481

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 5 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000262101, ENST00000350896, ENST00000355282, ENST00000381998, ENST00000445506, ENST00000517522, ENST00000518026, ENST00000518343, ENST00000518960, ENST00000519060, ENST00000520846, ENST00000521876, ENST00000522130, ENST00000522672, ENST00000858458, ENST00000858459

RefSeq mRNA: 4 — MANE Select: NM_138715 NM_001363744, NM_002445, NM_138715, NM_138716

CCDS: CCDS5995, CCDS5996, CCDS5997, CCDS87581

Canonical transcript exons

ENST00000262101 — 10 exons

Exon	Start	End
ENSE00001087899	16120418	16120606
ENSE00001087906	16175187	16175300
ENSE00001087908	16168458	16168870
ENSE00001872130	16107881	16110218
ENSE00002105539	16192598	16192651
ENSE00003473041	16177886	16177992
ENSE00003486209	16164065	16164251
ENSE00003488987	16150231	16150311
ENSE00003494846	16143558	16143611
ENSE00003546648	16155064	16155144

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 93.71.

FANTOM5 (CAGE): breadth broad, TPM avg 11.6936 / max 495.6985, expressed in 471 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91963	8.2179	360
91964	2.4070	285
91965	0.4537	122
91969	0.1647	50
91962	0.1627	108
91971	0.1078	36
91961	0.0814	47
91972	0.0722	22
91973	0.0174	9
91970	0.0088	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	93.71	gold quality
upper lobe of left lung	UBERON:0008952	92.24	gold quality
upper lobe of lung	UBERON:0008948	91.06	gold quality
gall bladder	UBERON:0002110	90.95	gold quality
calcaneal tendon	UBERON:0003701	89.81	gold quality
right coronary artery	UBERON:0001625	87.83	gold quality
visceral pleura	UBERON:0002401	87.76	gold quality
descending thoracic aorta	UBERON:0002345	87.38	gold quality
lung	UBERON:0002048	87.18	gold quality
monocyte	CL:0000576	84.97	gold quality
thoracic aorta	UBERON:0001515	84.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.89	gold quality
ascending aorta	UBERON:0001496	84.47	gold quality
layer of synovial tissue	UBERON:0007616	84.45	gold quality
mononuclear cell	CL:0000842	84.13	gold quality
omental fat pad	UBERON:0010414	83.66	gold quality
amniotic fluid	UBERON:0000173	83.59	gold quality
peritoneum	UBERON:0002358	83.55	gold quality
left adrenal gland	UBERON:0001234	83.38	gold quality
left coronary artery	UBERON:0001626	83.30	gold quality
tendon	UBERON:0000043	83.23	gold quality
synovial joint	UBERON:0002217	83.05	gold quality
leukocyte	CL:0000738	83.03	gold quality
left adrenal gland cortex	UBERON:0035825	82.99	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.92	gold quality
colonic epithelium	UBERON:0000397	82.68	gold quality
adipose tissue of abdominal region	UBERON:0007808	82.65	gold quality
right adrenal gland cortex	UBERON:0035827	82.41	gold quality
smooth muscle tissue	UBERON:0001135	82.39	gold quality
coronary artery	UBERON:0001621	81.77	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	2227.16
E-MTAB-6678	yes	939.84
E-GEOD-76312	yes	209.38
E-MTAB-6701	yes	64.39
E-GEOD-84465	yes	42.28
E-GEOD-135922	yes	38.81
E-ANND-3	yes	34.58
E-GEOD-134144	yes	25.76
E-GEOD-130148	yes	25.19
E-MTAB-10553	yes	24.78
E-CURD-119	yes	23.46
E-HCAD-9	yes	17.11
E-CURD-112	yes	14.45
E-MTAB-6386	no	11.81

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
SCARB1	Repression

Upstream regulators (CollecTRI, top): AP1, CEBPA, CEBPB, ETS2, GLI2, IRF6, JUN, NCOA3, NFKB, PPARG, SPI1, STAT1, STAT2

Literature-anchored findings (GeneRIF, showing 40)

• results show that MSR1 may be important in susceptibility to prostate cancer in men of both African American and European descent (PMID:12244320)
• Common sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk (PMID:12471593)
• there is a critical role for the membrane-proximal amino acids in SR-A trafficking and SR-A-mediated adhesion and internalization requires distinct cytoplasmic domains (PMID:12819208)
• Rare mutations of this receptor are associated with increased prostate cancer susceptibility among African-American men. (PMID:12839931)
• results do not support MSR1 as a risk factor for prostate cancer (PMID:12958598)
• MSR1 is induced in macrophages by oxidative stress and may enteract with reactive oxygen intermediates and may have a function in prostate cancer development. (PMID:14695991)
• Mutations in MSR1 gene might play a role in prostate cancer susceptibility, particularly the R293X mutation (PMID:15042613)
• reactive oxygen species generated from a protein kinase C-dependent NAD(P)H oxidase pathway plays a role in the high glucose-induced up-regulation of SR-A (PMID:15556945)
• Single nucleotide polymorphisms associated with hereditary prostate cancer. (PMID:16114055)
• Increased expression of macrophage scavenger receptor is associated with high level of serum IL-6 in colon cancer patients. (PMID:16144911)
• This study is the first to demonstrate further loss of function variants of MSR1 apart from R293X (nonsense mutation). (PMID:16287155)
• PAF enhances its own receptor expression and then increases lipid accumulation by dysregulating LDL receptor regulation and inducing scavenger receptor expression in mesangial cells (PMID:16750665)
• Hook3 interacts with a cytoplasmic domain of scavenger receptor A (PMID:17237231)
• Macrophage Scavenger Receptor-1 (MSR1) were also genotyped in the family-based study. A coding variant (Pro275Ala) was marginally associated with two qualitative airflow obstruction traits (p < or = 0.02). (PMID:17361499)
• SR-A is a novel cell surface receptor for dsRNA, and therefore, SR-A may play a role in antiviral immune responses (PMID:17709607)
• MSR1 polymorphisms may play a role in prostate cancer etiology in Chinese men. (PMID:17768178)
• SR-A gene expression level in the PBMCs specifically increases in patients with acute coronary syndrome, and provides a predictive marker for a reattack of a cardiovascular event. (PMID:17945237)
• Our results do not support a role for RNASEL, or MSR1 mutations in advanced Asian-Indian PC (PMID:18436282)
• Decreased expression by OxLDL in PMA-differentiated THP-1 macrophages. Increased expression in plaque vs. nonplaque lesion areas in human carotid endarterectomy specimens (correlated with CD36 expression). (PMID:18827892)
• human protein S can inhibit the expression and activity of SR-A through Mer RTK in macrophages, suggesting that human protein S is a modulator for macrophage functions in uptaking of modified lipoproteins (PMID:18922854)
• mutations are associated with prostate cancer risk (PMID:19120472)
• the inhibitory activity of liver X receptor alpha, ATP-binding cassette transporter and macrophage scavenger receptor A by LPS may be related to the transformation of human macrophages into foam cells. (PMID:19261092)
• SR-AI and SR-AII mRNA in rheumatoid arthritis patients’ monocytes were 4-6-fold higher than in healthy controls. (PMID:19790077)
• Macrophage SR-A is found to recognize exchangeable apolipoproteins (Apo)A-I and ApoE in both lipid-free and lipid-associated form, suggesting the shared amphipathic alpha-helix as a potential recognition motif. (PMID:19911804)
• These findings reveal a novel mechanistic insight into an interrelationship between SR-A1 and TLR-3/-9 signaling in human cytomegalovirus-exposed monocytes. (PMID:19914718)
• The MSR1 association with COPD susceptibility, COPD-related measures of lung function, and abnormalities of macrophage function may account for significant COPD morbidity. (PMID:20081102)
• Our findings corroborate the involvement of ELAC2, MSR1, and RNASEL in the etiology of prostate cancer even in individuals without a family history. (PMID:20086112)
• SRA-1 is an endocytic receptor for hepatitis C virus non-structural protein 3 in dendritic cells. (PMID:20338659)
• Decreased infiltration of macrophage scavenger receptor-positive cells in initial negative biopsy specimens is correlated with positive repeat biopsies of the prostate. (PMID:20384632)
• CD36 and SR-A play an important role in platelet-induced foam cell formation from CD34(+) progenitor cells (PMID:20414830)
• Stromal macrophage expressing CD204 is associated with tumor aggressiveness in lung adenocarcinoma. (PMID:20802348)
• novel property of SR-AI as a complement receptor for iC3b-opsonized bacteria that can elicit cell signaling (PMID:21203986)
• IFNalpha priming up-regulated the expression of SR-A in human monocyte/macrophages, leading to increased lipid uptake and foam cell formation. (PMID:21280004)
• Pattern recognition scavenger receptor CD204 attenuates Toll-like receptor 4-induced NF-kappaB activation by directly inhibiting ubiquitination of tumor necrosis factor (TNF) receptor-associated factor 6. (PMID:21460221)
• Msr1 suppresses leukemia stem cells and chronic myeloid leukemia development. (PMID:21596859)
• Interleukin 10 abrogated the oxidized low density lipoprotein-induced SR-A mRNA expression by 50.2+/-3.9% and its protein by 45.6+/-1.9%. (PMID:21658363)
• Cytokine abnormality induced by SRA(+) cells playS an role in tissue injury, and platelet emboli or contraction band necrosis might have been the leading cause of death in our SUDI cases. (PMID:21790861)
• Identified a novel peptide antagonist selective for SR-AI which could be a valuable tool in SR-AI targeted imaging of atherosclerotic lesions. (PMID:22282357)
• Data suggest that pulmonary metastasis is corrected with levels of Geminin, cleaved caspase-3, CD44, E-cadherin, epidermal growth factor receptor, and CD204 in cancer cells within permeated lymphatic vessels. (PMID:22429811)
• In this review, we showed that SR-A and MARCO trigger intracellular signaling, modulating pro-inflammatory and microbicidal activities of macrophages. (PMID:22470185)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Msr1	ENSMUSG00000025044
rattus_norvegicus	Msr1	ENSRNOG00000012779

Paralogs (3): MARCO (ENSG00000019169), COLEC12 (ENSG00000158270), SCARA5 (ENSG00000168079)

Protein

Protein identifiers

Macrophage scavenger receptor types I and II — P21757 (reviewed: P21757)

Alternative names: Macrophage acetylated LDL receptor I and II, Scavenger receptor class A member 1

All UniProt accessions (6): B4DDJ5, E5RFI4, E5RFW8, E5RI91, H0YBY2, P21757

UniProt curated annotations — full annotation on UniProt →

Function. Membrane glycoproteins implicated in the pathologic deposition of cholesterol in arterial walls during atherogenesis. Two types of receptor subunits exist. These receptors mediate the endocytosis of a diverse group of macromolecules, including modified low density lipoproteins (LDL). Isoform III does not internalize acetylated LDL.

Subunit / interactions. Homotrimer. Interacts with MYO18A.

Subcellular location. Membrane.

Tissue specificity. Isoform I, isoform II and isoform III are expressed in monocyte-derived macrophages. Isoform I and isoform II are expressed in the liver, placenta and brain.

Disease relevance. Prostate cancer (PC) [MIM:176807] A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. The disease may be caused by variants affecting the gene represented in this entry. MSR1 variants may play a role in susceptibility to prostate cancer. MSR1 variants have been found in individuals with prostate cancer and co-segregate with the disease in some families. Barrett esophagus (BE) [MIM:614266] A condition characterized by a metaplastic change in which normal esophageal squamous epithelium is replaced by a columnar and intestinal-type epithelium. Patients with Barrett esophagus have an increased risk of esophageal adenocarcinoma. The main cause of Barrett esophagus is gastroesophageal reflux. The retrograde movement of acid and bile salts from the stomach into the esophagus causes prolonged injury to the esophageal epithelium and induces chronic esophagitis, which in turn is believed to trigger the pathologic changes. The disease may be caused by variants affecting the gene represented in this entry. Genetic variants in MSR1 have been found in individuals with Barrett esophagus and are thought to contribute to disease susceptibility.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (3)

UniProt ID	Names	Canonical?
P21757-1	I	yes
P21757-2	II
P21757-3	III

RefSeq proteins (4): NP_001350673, NP_002436, NP_619729, NP_619730 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001190	SRCR	Domain
IPR003543	SR-AI/II	Family
IPR008160	Collagen	Repeat
IPR036772	SRCR-like_dom_sf	Homologous_superfamily

Pfam: PF00530, PF01391, PF03523

UniProt features (44 total): sequence variant 10, glycosylation site 7, strand 7, disulfide bond 3, splice variant 3, helix 3, topological domain 2, domain 2, region of interest 2, chain 1, transmembrane region 1, turn 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7DPX	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21757-F1	67.74	0.20

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 (1): 27

Disulfide bonds (3): 375–439, 388–449, 419–429

Glycosylation sites (7): 82, 102, 143, 184, 221, 249, 267

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3000480	Scavenging by Class A Receptors
R-HSA-2173782	Binding and Uptake of Ligands by Scavenger Receptors
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 290 (showing top): GOBP_REGULATION_OF_LIPID_STORAGE, MCLACHLAN_DENTAL_CARIES_UP, GOCC_COLLAGEN_TRIMER, CROONQUIST_NRAS_SIGNALING_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_MACROPHAGE_DERIVED_FOAM_CELL_DIFFERENTIATION, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_PLASMA_LIPOPROTEIN_PARTICLE_CLEARANCE, FOSTER_TOLERANT_MACROPHAGE_DN, HOWLIN_PUBERTAL_MAMMARY_GLAND, MARTINEZ_RB1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, OCT1_06, COATES_MACROPHAGE_M1_VS_M2_UP, GATA1_04

GO Biological Process (11): receptor-mediated endocytosis (GO:0006898), phagocytosis, engulfment (GO:0006911), negative regulation of gene expression (GO:0010629), positive regulation of macrophage derived foam cell differentiation (GO:0010744), positive regulation of cholesterol storage (GO:0010886), cholesterol transport (GO:0030301), plasma lipoprotein particle clearance (GO:0034381), lipoprotein transport (GO:0042953), establishment of localization in cell (GO:0051649), amyloid-beta clearance (GO:0097242), endocytosis (GO:0006897)

GO Molecular Function (5): amyloid-beta binding (GO:0001540), scavenger receptor activity (GO:0005044), low-density lipoprotein particle binding (GO:0030169), cargo receptor activity (GO:0038024), protein binding (GO:0005515)

GO Cellular Component (5): collagen trimer (GO:0005581), plasma membrane (GO:0005886), membrane (GO:0016020), endocytic vesicle membrane (GO:0030666), low-density lipoprotein particle (GO:0034362)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Binding and Uptake of Ligands by Scavenger Receptors	1
Vesicle-mediated transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
multicellular organismal process	2
vesicle-mediated transport	2
endocytosis	1
phagocytosis	1
plasma membrane invagination	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
positive regulation of cell differentiation	1
cholesterol storage	1
positive regulation of lipid storage	1
regulation of cholesterol storage	1
sterol transport	1
receptor-mediated endocytosis	1
plasma lipoprotein particle disassembly	1
regulation of plasma lipoprotein particle levels	1
protein transport	1
lipoprotein localization	1
establishment of localization	1
cellular localization	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
peptide binding	1
cargo receptor activity	1
lipoprotein particle binding	1
molecular_function	1
molecular adaptor activity	1
binding	1
protein-containing complex	1
membrane	1
cell periphery	1
cellular anatomical structure	1
endocytic vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
plasma lipoprotein particle	1

Protein interactions and networks

STRING

2178 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MSR1	SCARB1	Q8WTV0	815
MSR1	CD36	P16671	792
MSR1	SCARB2	Q14108	791
MSR1	APOE	P02649	726
MSR1	CD68	P34810	724
MSR1	MRC1	P22897	721
MSR1	OLR1	P78380	713
MSR1	ELAC2	Q9BQ52	713
MSR1	TLR2	O60603	674
MSR1	RNASEL	Q05823	654
MSR1	PRKCSH	P14314	632
MSR1	DDOST	P39656	628
MSR1	IL10	P22301	611
MSR1	CD47	Q08722	585
MSR1	CCT4	P50991	570

IntAct

47 interactions, top by confidence:

A	B	Type	Score
NKG7	MSR1	psi-mi:“MI:0915”(physical association)	0.780
MSR1	SEC22A	psi-mi:“MI:0915”(physical association)	0.780
MSR1	NKG7	psi-mi:“MI:0915”(physical association)	0.780
SEC22A	MSR1	psi-mi:“MI:0915”(physical association)	0.780
ATP6V0C	MSR1	psi-mi:“MI:0915”(physical association)	0.720
MALL	MSR1	psi-mi:“MI:0915”(physical association)	0.720
MSR1	MALL	psi-mi:“MI:0915”(physical association)	0.720
MSR1	ATP6V0C	psi-mi:“MI:0915”(physical association)	0.720
LEPROTL1	MSR1	psi-mi:“MI:0915”(physical association)	0.670
LEPROTL1	MSR1	psi-mi:“MI:0915”(physical association)	0.560
MSR1	LEPROTL1	psi-mi:“MI:0915”(physical association)	0.560
MSR1	FA2H	psi-mi:“MI:0915”(physical association)	0.560
HOOK3	MSR1	psi-mi:“MI:0915”(physical association)	0.520
MSR1	HOOK3	psi-mi:“MI:0915”(physical association)	0.520
AABR07026291.1	MSR1	psi-mi:“MI:0915”(physical association)	0.510
MSR1	AABR07026291.1	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (34): MSR1 (Two-hybrid), NKG7 (Two-hybrid), MALL (Two-hybrid), LEPROTL1 (Two-hybrid), SEC22A (Two-hybrid), IKBIP (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COLGALT2 (Affinity Capture-MS), FA2H (Two-hybrid), LEPROTL1 (Two-hybrid), NKG7 (Two-hybrid), SEC22A (Two-hybrid), MALL (Two-hybrid), ATP6V0C (Two-hybrid), MSR1 (Affinity Capture-Western)

ESM2 similar proteins: A2AV25, A5PJQ2, A5PMY6, A6H6E2, B7ZNG0, O00548, O35764, O43278, O70340, O95502, P21757, P21758, P30204, P47970, P47971, P47972, P48759, P58660, P59900, P97738, Q05585, Q15818, Q24K15, Q2M1P5, Q5RFW0, Q61483, Q62443, Q6AZY7, Q6MG84, Q6ZMJ2, Q86VZ4, Q8BJS4, Q8C850, Q8CB67, Q8K299, Q8N539, Q8NI99, Q8R0Z6, Q95LU3, Q96NZ8

Diamond homologs: A1L0T3, A1L1V4, A1L4H1, A5PJQ2, A6H737, A7E3W2, B4F6N6, B5DF27, B8A4W9, E1C3U7, F1QQC3, F1RD85, F7J220, G3V801, M9NDE3, O08762, O43866, O70513, P21757, P21758, P30203, P30204, P30205, P56730, P58022, P58215, P70117, P85521, Q05585, Q07797, Q08380, Q08B63, Q14DK5, Q24JV9, Q2VL90, Q2VLG4, Q2VLG6, Q2VLH6, Q4A3R3, Q4G0T1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HOOK3	down-regulates	MSR1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	7
Uncertain significance	84
Likely benign	14
Benign	15

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
29779	NM_138715.3(MSR1):c.760C>G (p.Leu254Val)	Pathogenic
502674	NM_138715.3(MSR1):c.1033+1G>C	Pathogenic
2445354	NM_138715.3(MSR1):c.905C>A (p.Pro302Gln)	Likely pathogenic
2445365	NM_138715.3(MSR1):c.68T>G (p.Phe23Cys)	Likely pathogenic
2445374	NM_138715.3(MSR1):c.722A>G (p.Lys241Arg)	Likely pathogenic
2445377	NM_138715.3(MSR1):c.1223G>C (p.Gly408Ala)	Likely pathogenic
4526862	NM_138715.3(MSR1):c.31C>T (p.Gln11Ter)	Likely pathogenic
4526863	NM_138715.3:c.688_1356del	Likely pathogenic
624315	NM_138715.3(MSR1):c.818-1G>A	Likely pathogenic

SpliceAI

1505 predictions. Top by Δscore:

Variant	Effect	Δscore
8:16143556:A:AC	donor_gain	1.0000
8:16143557:C:CC	donor_gain	1.0000
8:16150225:TAATA:T	donor_loss	1.0000
8:16150227:ATACC:A	donor_loss	1.0000
8:16150228:TACC:T	donor_loss	1.0000
8:16150229:A:C	donor_loss	1.0000
8:16150230:C:A	donor_loss	1.0000
8:16150317:T:TC	acceptor_gain	1.0000
8:16155059:CATA:C	donor_loss	1.0000
8:16155060:ATAC:A	donor_loss	1.0000
8:16155061:TA:T	donor_loss	1.0000
8:16155062:A:AG	donor_loss	1.0000
8:16155063:C:CA	donor_loss	1.0000
8:16164059:TTTTA:T	donor_loss	1.0000
8:16164060:TTTA:T	donor_loss	1.0000
8:16164061:TTACC:T	donor_loss	1.0000
8:16164062:TACCT:T	donor_loss	1.0000
8:16164063:ACCTT:A	donor_loss	1.0000
8:16164064:CCTT:C	donor_loss	1.0000
8:16164248:TTTC:T	acceptor_gain	1.0000
8:16177878:CTACT:C	donor_loss	1.0000
8:16177879:TACTT:T	donor_loss	1.0000
8:16177880:ACTTA:A	donor_loss	1.0000
8:16177881:CTT:C	donor_loss	1.0000
8:16177882:TTACT:T	donor_loss	1.0000
8:16177883:TACTC:T	donor_loss	1.0000
8:16177884:A:AC	donor_gain	1.0000
8:16177884:ACT:A	donor_gain	1.0000
8:16177884:ACTCG:A	donor_loss	1.0000
8:16177885:C:A	donor_loss	1.0000

AlphaMissense

2982 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:16120503:C:A	W379C	0.999
8:16120503:C:G	W379C	0.999
8:16120527:C:A	W371C	0.999
8:16120527:C:G	W371C	0.999
8:16120477:C:G	C388S	0.998
8:16120478:A:T	C388S	0.998
8:16110095:C:G	C449S	0.997
8:16110096:A:T	C449S	0.997
8:16110184:A:C	C419W	0.997
8:16120425:A:C	F405L	0.997
8:16120425:A:T	F405L	0.997
8:16120427:A:G	F405L	0.997
8:16120476:A:C	C388W	0.997
8:16120477:C:T	C388Y	0.997
8:16120478:A:G	C388R	0.997
8:16120505:A:G	W379R	0.997
8:16120505:A:T	W379R	0.997
8:16120516:C:T	C375Y	0.997
8:16110094:G:C	C449W	0.996
8:16110096:A:G	C449R	0.996
8:16110155:C:G	C429S	0.996
8:16110156:A:T	C429S	0.996
8:16110185:C:G	C419S	0.996
8:16110186:A:G	C419R	0.996
8:16110186:A:T	C419S	0.996
8:16120515:A:C	C375W	0.996
8:16120516:C:G	C375S	0.996
8:16120517:A:G	C375R	0.996
8:16120517:A:T	C375S	0.996
8:16110156:A:G	C429R	0.995

dbSNP variants (sampled 300 via entrez): RS1000006886 (8:16176436 G>A,C), RS1000049941 (8:16184935 T>C), RS1000050938 (8:16157024 T>A), RS1000052988 (8:16141273 T>C), RS1000055502 (8:16182008 T>A), RS1000100753 (8:16130363 T>G), RS1000106425 (8:16161574 A>C), RS1000141504 (8:16188910 C>G,T), RS1000141982 (8:16175668 A>G), RS1000155039 (8:16150653 T>C), RS1000171940 (8:16153035 T>A), RS1000181117 (8:16180187 T>C), RS1000193931 (8:16148009 A>G), RS1000199476 (8:16158030 T>C), RS1000204796 (8:16150863 C>CACAG)

Disease associations

OMIM: gene MIM:153622 | disease phenotypes: MIM:301050, MIM:614266, MIM:167000

GenCC curated gene-disease

Disease	Classification	Inheritance
Barrett esophagus	Limited	Unknown

Mondo (7): prostate cancer (MONDO:0008315), X-linked Alport syndrome (MONDO:0010520), Barrett esophagus (MONDO:0013662), hereditary neoplastic syndrome (MONDO:0015356), primary ovarian failure (MONDO:0005387), ovarian cancer (MONDO:0008170), carcinoma of esophagus (MONDO:0019086)

Orphanet (9): Familial prostate cancer (Orphanet:1331), Inherited cancer-predisposing syndrome (Orphanet:140162), Alport syndrome (Orphanet:63), X-linked Alport syndrome (Orphanet:88917), Adenocarcinoma of the oesophagus and oesophagogastric junction (Orphanet:99976), Rare ovarian cancer (Orphanet:213500), Carcinoma of esophagus (Orphanet:70482), NON RARE IN EUROPE: Barrett esophagus (Orphanet:1232), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0001442	Typified by somatic mosaicism
HP:0002020	Gastroesophageal reflux
HP:0004791	Esophageal ulceration
HP:0011459	Esophageal carcinoma
HP:0100580	Barrett esophagus

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST003121_17	Alcohol dependence	9.000000e-06
GCST008156_145	Hip circumference adjusted for BMI	9.000000e-06
GCST008478_30	Neurological blood protein biomarker levels	1.000000e-14
GCST009159_8	Blood protein levels	6.000000e-10
GCST010244_182	Triglyceride levels	2.000000e-08
GCST011743_46	HDL cholesterol levels in HIV infection	1.000000e-06
GCST90020025_372	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020027_1331	Waist-hip index	5.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0004747	protein measurement
EFO:0010241	galectin-3-binding protein measurement
EFO:0004530	triglyceride measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001471	Barrett Esophagus	C04.834.154; C06.405.117.102
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5811 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.25	IC50	5600	nM	RIGIDONE

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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
3-hydroxy-5-methyl-2-[(2S)-6-methylhept-5-en-2-yl]cyclohexa-2,5-diene-1,4-dione	402862: Inhibition of full-length MSR1 transfected in HEK293 cells by fluorimetry	ic50	5.6000	uM

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	affects cotreatment, decreases reaction, increases expression	5
Resveratrol	decreases reaction, increases expression, decreases expression, decreases uptake	3
sodium arsenite	affects methylation, increases expression	2
Arsenic Trioxide	increases expression, decreases expression, decreases reaction	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
TEMPO	decreases reaction, increases expression	1
bisphenol A	increases methylation	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
bisdemethoxycurcumin	decreases reaction, increases expression	1
1,3-dimethylthiourea	decreases reaction, increases expression	1
demethoxycurcumin	decreases reaction, increases expression	1
acetovanillone	decreases reaction, increases expression	1
tamibarotene	decreases reaction, increases expression	1
N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester	decreases expression, decreases reaction, increases abundance	1
FSL-1 lipoprotein, synthetic	increases expression, decreases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
malondialdehyde-low density lipoprotein, human	decreases reaction, increases expression	1
Calcimycin	increases expression, increases reaction, affects cotreatment	1
Atorvastatin	affects cotreatment, increases expression	1
Rosiglitazone	increases expression, affects cotreatment	1
Decitabine	decreases expression, decreases reaction	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance, decreases reaction	1
Allergens	decreases expression	1
Calcitriol	decreases expression	1
Carmustine	decreases expression	1
Cholesterol	decreases expression, decreases uptake	1
Curcumin	decreases reaction, increases expression	1
Cycloheximide	decreases reaction, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL997334	Binding	Inhibition of full-length MSR1 transfected in HEK293 cells by fluorimetry	Rigidone, a sesquiterpene o-quinone from the gorgonian Pseudopterogorgia rigida. — J Nat Prod

Cellosaurus cell lines

13 cell lines: 10 transformed cell line, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8KX	Abcam HCT 116 MSR1 KO	Cancer cell line	Male
CVCL_B8Z4	Abcam MCF-7 MSR1 KO	Cancer cell line	Female
CVCL_B9N4	Abcam A-549 MSR1 KO	Cancer cell line	Male
CVCL_KS18	Flp-In-293-MSR	Transformed cell line	Female
CVCL_KS19	T-REx-293-MSR	Transformed cell line	Female
CVCL_U428	GripTite 293 MSR	Transformed cell line	Female
CVCL_ZI83	GeneBLAzer UAS-bla GripTite 293	Transformed cell line	Female
CVCL_ZI94	GeneBLAzer AR-UAS-bla Griptite 293	Transformed cell line	Female
CVCL_ZI95	GeneBLAzer ERalpha-UAS-bla GripTite 293	Transformed cell line	Female
CVCL_ZI96	GeneBLAzer ERbeta-UAS-bla GripTite 293	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00352261	PHASE4	COMPLETED	An Open Label pH Comparison of Esomeprazole and Lansoprazole in Barrett’s Esophagus Patients
NCT00526786	PHASE4	TERMINATED	Study of CryoSpray Ablation of Low Grade or High Grade Dysplasia Within Barrett’s Esophagus
NCT00628784	PHASE4	UNKNOWN	Endoesophageal Cryotherapy For Ablating Barrett’s Esophagus and Early Stage Esophageal Cancer
NCT00637559	PHASE4	COMPLETED	Barrett’s Esophagus - 315 - 3 Way Cross-Over
NCT00637988	PHASE4	COMPLETED	Barrett’s Esophagus - 315 - 3 Way Cross Over
NCT00754468	PHASE4	COMPLETED	Study of CryoSpray Ablation(TM)to Determine Treatment Effect, Depth of Injury, and Side Effects in the Esophagus.
NCT00872755	PHASE4	COMPLETED	Nissen and Gastroplasty in Gastroesophageal Reflux Disease (GERD)
NCT01030263	PHASE4	TERMINATED	A Trial Comparing Yield of Confocal Endomicroscopy Guided Biopsies
NCT01093755	PHASE4	COMPLETED	Does Intensive Acid Suppression Reduce Esophageal Inflammation and Recurrent Barrett’s Esophagus Following Ablation?
NCT01733147	PHASE4	COMPLETED	Modulation of Esophageal Inflammation in Barrett’s Esophagus by Omega-3 Fatty Acids
NCT02004782	PHASE4	WITHDRAWN	Barretts oEsophageal Resection With Steroid Therapy Trial
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration