MRC1

Summary

MRC1 (mannose receptor C-type 1, HGNC:7228) is a protein-coding gene on chromosome 10p12.33, encoding Macrophage mannose receptor 1 (P22897). Mediates the endocytosis of glycoproteins by macrophages.

The recognition of complex carbohydrate structures on glycoproteins is an important part of several biological processes, including cell-cell recognition, serum glycoprotein turnover, and neutralization of pathogens. The protein encoded by this gene is a type I membrane receptor that mediates the endocytosis of glycoproteins by macrophages. The protein has been shown to bind high-mannose structures on the surface of potentially pathogenic viruses, bacteria, and fungi so that they can be neutralized by phagocytic engulfment.

Source: NCBI Gene 4360 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 6 total
• Druggable target: yes
• MANE Select transcript: NM_002438

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7228
Approved symbol	MRC1
Name	mannose receptor C-type 1
Location	10p12.33
Locus type	gene with protein product
Status	Approved
Aliases	CLEC13D, CD206, bA541I19.1, CLEC13DL
Ensembl gene	ENSG00000260314
Ensembl biotype	protein_coding
OMIM	153618
Entrez	4360

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000569591, ENST00000884127, ENST00000884128, ENST00000884129, ENST00000954013, ENST00000954014

RefSeq mRNA: 1 — MANE Select: NM_002438 NM_002438

CCDS: CCDS7123

Canonical transcript exons

ENST00000569591 — 30 exons

Exon	Start	End
ENSE00002575602	17856242	17856352
ENSE00002578276	17863534	17863682
ENSE00002581788	17823074	17823475
ENSE00002582955	17840693	17840806
ENSE00002583864	17906886	17906999
ENSE00002585085	17885269	17885435
ENSE00002586202	17879721	17879821
ENSE00002586791	17871982	17872126
ENSE00002588991	17809348	17809526
ENSE00002589552	17898034	17898266
ENSE00002591542	17845289	17845435
ENSE00002593917	17866562	17866761
ENSE00002597157	17877900	17877967
ENSE00002597262	17900788	17900953
ENSE00002602710	17875090	17875253
ENSE00002602940	17909306	17909347
ENSE00002603063	17827542	17827715
ENSE00002603873	17881067	17881181
ENSE00002609457	17910215	17911164
ENSE00002611376	17861387	17861502
ENSE00002612392	17870246	17870373
ENSE00002612851	17870848	17870935
ENSE00002615950	17907534	17907698
ENSE00002618071	17852967	17853124
ENSE00002624582	17849579	17849764
ENSE00002625480	17901973	17902122
ENSE00002626628	17880525	17880670
ENSE00002627496	17833675	17833839
ENSE00002628950	17873784	17873825
ENSE00002629004	17894210	17894312

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.06.

FANTOM5 (CAGE): breadth broad, TPM avg 15.8798 / max 2298.6247, expressed in 427 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
205753	14.8543	417
205752	0.9496	238
205769	0.0760	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	99.06	gold quality
visceral pleura	UBERON:0002401	98.42	gold quality
secondary oocyte	CL:0000655	98.39	gold quality
oocyte	CL:0000023	96.05	gold quality
decidua	UBERON:0002450	95.34	gold quality
pericardium	UBERON:0002407	95.09	gold quality
pleura	UBERON:0000977	94.82	gold quality
superficial temporal artery	UBERON:0001614	94.34	gold quality
layer of synovial tissue	UBERON:0007616	93.64	gold quality
placenta	UBERON:0001987	93.60	gold quality
lung	UBERON:0002048	93.57	gold quality
synovial joint	UBERON:0002217	93.41	gold quality
skin of hip	UBERON:0001554	93.16	gold quality
heart right ventricle	UBERON:0002080	92.91	gold quality
parietal pleura	UBERON:0002400	92.69	gold quality
mammary duct	UBERON:0001765	92.61	gold quality
myocardium	UBERON:0002349	91.55	gold quality
upper lobe of lung	UBERON:0008948	91.54	gold quality
right lung	UBERON:0002167	91.52	gold quality
left ventricle myocardium	UBERON:0006566	91.15	gold quality
cauda epididymis	UBERON:0004360	91.13	gold quality
upper lobe of left lung	UBERON:0008952	91.02	gold quality
spleen	UBERON:0002106	90.85	gold quality
adult organism	UBERON:0007023	90.79	gold quality
calcaneal tendon	UBERON:0003701	90.41	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.35	gold quality
gall bladder	UBERON:0002110	89.81	gold quality
trabecular bone tissue	UBERON:0002483	89.56	gold quality
epithelium of mammary gland	UBERON:0003244	89.30	gold quality
upper leg skin	UBERON:0004262	89.30	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	3829.83
E-GEOD-130148	yes	3137.40
E-HCAD-36	yes	1758.10
E-GEOD-84465	yes	969.88
E-GEOD-135922	yes	805.18
E-MTAB-10855	yes	705.82
E-MTAB-8530	yes	592.78
E-MTAB-5061	yes	195.82
E-HCAD-1	yes	97.41
E-CURD-122	yes	73.72
E-MTAB-6701	yes	50.20
E-MTAB-10553	yes	48.48
E-HCAD-10	yes	48.04
E-ANND-3	yes	38.60
E-CURD-46	yes	31.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNMT1, FOXO1, HIF1A, IFNG, IL4, PPARG, SPI1, STAT6

miRNA regulators (miRDB)

67 targeting MRC1, 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-4668-3P	100.00	68.74	2635
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
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-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-33A-3P	99.70	70.27	3362

Literature-anchored findings (GeneRIF, showing 40)

• reduced expression in Mycobacterium tuberculosis-infected human macrophages exhibiting enhanced cellular adhesion (PMID:12368450)
• Engagement of the endocytic C-type 1 mannose receptor elicits a secretory program in dendritic cells characterized by a repertoire of anti-inflammatory cytokines and chemokines and the ability to inhibit the generation of Th1-polarized immune responses. (PMID:14568928)
• alveolar macrophage mannose receptor mediates Pneumocystis mediated NF-kB nuclear translocation and may represent an important mechanism of the host cell response to Pneumocystis infection (PMID:15155616)
• Endocytosis of glycosylated protein by the mannose receptor does not enhance presentation of antigen. The postulated role of the mannose receptor in presentation of glycoprotein-derived antigen is reevaluated in light of these results. (PMID:15190005)
• MR is a binding receptor, which requires a partner to trigger phagocytosis in some specialized cells such as macrophages. (PMID:15767290)
• The mannose receptors on human AM may suppress select proinflammatory cytokine release and may serve to regulate the innate inflammatory responses to infectious challenge in the lungs. (PMID:16000387)
• Engagement of the Mannose Receptor by mannose-capped lipoarabinomannan during the phagocytic process directs Mycobacterium tuberculosis to its initial phagosomal niche, thereby enhancing survival in human macrophages. (PMID:16203868)
• Pc-mediated IL-8 release by human AM requires the coexpression of MR and TLR2 and further supports the concept that combinatorial interactions of macrophage innate receptors provide specificity of host defense cell responses to infectious challenge. (PMID:17020928)
• Mannose receptor (MR) may serve as a binding and an entry site, but the MR-mediated pathway does not lead to productive HIV-1 infection. (PMID:17360361)
• demonstrate that entry of FVIII into human dendritic cells (DC) leading to T cell activation, is mediated by mannose-terminating glycans on FVIII (PMID:17502612)
• RAGE could also behave as a receptor for Mycobacterium tuberculosis (PMID:18279703)
• The expressions of CD105, DC-SIGN and MMR were the strongest in decidua basalis of mid pregnancy and indicate the importance of decidual macrophages in tissue homeostasis at the uteroplacental interface. (PMID:18353434)
• The mannose receptor and hCG were colocalized on the surface of uterine natural killer cells. (PMID:19196802)
• The studies provide the first demonstration of a significant role for mannose receptor, synergistic with TLR2, in activating a proinflammatory response to P. aeruginosa infection. (PMID:19197942)
• macrophage mannose receptor oligomerization enhances gp120-mediated binding of HIV-1 (PMID:19224860)
• Expansion of small sputum macrophages in cystic fibrosis shows a failure to express MARCO and CD206. (PMID:19403625)
• These data suggest that in hepatitis B virus infected patients, mannose receptor-mediated interaction between HBsAg and dendritic cells and subsequent impairment of dendritic cells predominantly occurs at the main site of infection, the liver. (PMID:19683778)
• Data show that macrophages cocultured with MSCs consistently showed high-level expression of CD206, a marker of alternatively activated macrophages. (PMID:19772890)
• Results suggest that sequence variations in the MRC1 gene are associated with the development of asthma in two independent and ethnically diverse populations. (PMID:19902202)
• A significant association of exon 7 encoded amino acid haplotypes with leprosy per se (P = 0.012) and multibacillary leprosy (P = 0.004). (PMID:20035344)
• Data identify a new molecular pathway that links engagement of the mannose receptor, an important pattern recognition receptor for M. tuberculosis, with PPARgamma activation, which regulates the macrophage inflammatory response. (PMID:20554962)
• MR plays a key role in the T helper type (Th)2 cell polarization observed after dust mite glycoallergen Der p 1 exposure through regulation of indoleamine 2,3-dioxygenase activity. (PMID:20610655)
• This is the first study to imply that genetic variants in MRC1, a major member of the C-type lectin, contribute to the development of sarcoidosis. (PMID:21029423)
• Studies show that tumoral mucin-mediated ligation of the MR on infiltrating TAM may contribute to their immune suppressive phenotype. (PMID:21331365)
• MMR distribution in liver, spleen, lung, kidney, heart, diaphragm, quadriceps, and triceps in these animal models and compared them with MMR distribution in wild-type mice. (PMID:21416197)
• hMR expressed by vaginal epithelial cells has high affinity for HIV gp120 and this binding induces production of matrix metalloproteinases. (PMID:22132194)
• Sugar moieties on ADAMTS13 interact with MR, thereby promoting its endocytosis by antigen presenting cells. (PMID:22289891)
• elderly subjects had twofold higher CD68 and CD206 gene expression (both P < 0.002) than young participants. In both studies, CD68(+) muscle macrophages were not associated with BMI (PMID:22314623)
• results failed to confirm the reported association between MRC1 variant rs1926736 and IFNG variant rs2430561 and leprosy in Han Chinese; however variants rs692527 and rs34856358 of the MRC1 gene were associated with paucibacillary leprosy and rs3138557 of the IFNG gene was significantly associated with multibacillary leprosy (PMID:22392581)
• The frequency of MRC1 allele G1186A (rs34039386)in a Chinese population was higher in the pulmonary tuberculosis group than controls. No association was found for G1195A, T1212C, C1221G, C1303T or C1323T. (PMID:22393309)
• The mannose receptor found on the novel hybridoma cell has endocytic characteristics consistent with and similar to the mannose receptor found on the surface of monocyte-derived human macrophages. (PMID:22967244)
• The presence of human mannose receptor in a smaller number of vaginal epithelial cells of serodiscordant females prevented binding and HIV entry into these cells and therefore prevented sexual transmission of HIV. (PMID:23148569)
• The molecular association of the macrophage mannose receptor (MR) with HSP70 family members via the receptor cytoplasmic tail may contribute to MR trafficking in macrophages. (PMID:23345393)
• Report CD44/macrophage mannose receptor as a ligand/receptor pair involved in the process of lymphocyte transit via the lymphatic vasculature. (PMID:23603511)
• Novel MRC1 gene polymorphisms are associated with susceptibility to pulmonary tuberculosis in Chinese Uygur and Kazak populations. (PMID:23653008)
• Data suggest a role for CD206 in regulating allergen induced allergic responses in asthma. (PMID:23734186)
• The MRC1/CD68 ratio is positively associated with adipose tissue lipogenesis and with muscle mitochondrial gene expression in humans. (PMID:23951013)
• presence of soluble form of MR in human serum in critical illness (PMID:24114918)
• confers responsivenes to CpG-motif containing oligodeoxynucleotides in macrophages (PMID:24184555)
• There was a significant negative correlation between the number of CD163(+), CD204(+) or CD206(+) alveolar macrophages. (PMID:24498098)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrc1b	ENSDARG00000038822
danio_rerio	mrc1a	ENSDARG00000102100
mus_musculus	Mrc1	ENSMUSG00000026712
rattus_norvegicus	Mrc1	ENSRNOG00000018251

Paralogs (4): MRC2 (ENSG00000011028), LY75 (ENSG00000054219), PLA2R1 (ENSG00000153246), CD302 (ENSG00000241399)

Protein

Protein identifiers

Macrophage mannose receptor 1 — P22897 (reviewed: P22897)

Alternative names: C-type lectin domain family 13 member D, C-type lectin domain family 13 member D-like, Human mannose receptor, Macrophage mannose receptor 1-like protein 1

All UniProt accessions (1): P22897

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the endocytosis of glycoproteins by macrophages. Binds both sulfated and non-sulfated polysaccharide chains. (Microbial infection) Acts as a phagocytic receptor for bacteria, fungi and other pathogens. (Microbial infection) Acts as a receptor for Dengue virus envelope protein E. (Microbial infection) Interacts with Hepatitis B virus envelope protein.

Subunit / interactions. (Microbial infection) Interacts with Dengue virus. (Microbial infection) May act as a receptor for hepatitis B virus, enabling uptake of the virus in hepatic dendritic cells.

Subcellular location. Endosome membrane. Cell membrane.

Domain organisation. The C-type lectin domains, also called carbohydrate-recognition domains or CRDs, 1-3 have at most very weak affinity for carbohydrates. C-type lectin domain 4 shows the highest affinity binding and has multispecificity for a variety of monosaccharides. At least 3 C-type lectin domains (4, 5, and 7) are required for high affinity binding and endocytosis of multivalent glycoconjugates.

Polymorphism. Genetic variations in MRC1 may influence susceptibility or resistance to leprosy in some populations. Particularly, Gly-396 seems to be a risk factor for leprosy when associated with Ala-399 and Phe-407.

Isoforms (2)

UniProt ID	Names	Canonical?
P22897-1	1	yes
P22897-2	2

RefSeq proteins (1): NP_002429* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000562	FN_type2_dom	Domain
IPR000772	Ricin_B_lectin	Domain
IPR001304	C-type_lectin-like	Domain
IPR013806	Kringle-like	Homologous_superfamily
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR018378	C-type_lectin_CS	Conserved_site
IPR035992	Ricin_B-like_lectins	Homologous_superfamily
IPR036943	FN_type2_sf	Homologous_superfamily
IPR050111	C-type_lectin/snaclec_domain	Family

Pfam: PF00040, PF00059, PF24562

UniProt features (133 total): strand 53, disulfide bond 21, helix 18, turn 12, domain 10, glycosylation site 7, sequence variant 4, topological domain 2, splice variant 2, signal peptide 1, chain 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
7JUB	X-RAY DIFFRACTION	1.2
7L67	X-RAY DIFFRACTION	1.2
7L61	X-RAY DIFFRACTION	1.35
7L64	X-RAY DIFFRACTION	1.35
7L65	X-RAY DIFFRACTION	1.35
7JUC	X-RAY DIFFRACTION	1.4
7JUD	X-RAY DIFFRACTION	1.4
7JUE	X-RAY DIFFRACTION	1.4
7JUF	X-RAY DIFFRACTION	1.4
7JUG	X-RAY DIFFRACTION	1.4
7JUH	X-RAY DIFFRACTION	1.4
7L68	X-RAY DIFFRACTION	1.4
7L62	X-RAY DIFFRACTION	1.55
7L63	X-RAY DIFFRACTION	1.65
7L66	X-RAY DIFFRACTION	1.75
5XTS	X-RAY DIFFRACTION	2
1EGG	X-RAY DIFFRACTION	2.3
1EGI	X-RAY DIFFRACTION	2.3
6INU	X-RAY DIFFRACTION	2.65
6IOE	X-RAY DIFFRACTION	2.9
6INN	X-RAY DIFFRACTION	3
6INO	X-RAY DIFFRACTION	3.05
5XTW	X-RAY DIFFRACTION	3.2
6INV	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22897-F1	82.57	0.45

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 (21): 35–49, 74–91, 168–194, 182–209, 247–340, 316–332, 391–486, 463–478, 532–625, 600–617, 646–659, 680–777, 753–769, 828–922, 899–914, 977–1079, 1052–1071, 1123–1212, 1190–1204, 1263–1355 …

Glycosylation sites (7): 104, 344, 529, 926, 930, 1160, 1205

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-1236978	Cross-presentation of soluble exogenous antigens (endosomes)
R-HSA-9637628	Modulation by Mtb of host immune system
R-HSA-9918485	Dengue Virus Attachment and Entry
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-5663205	Infectious disease
R-HSA-9635486	Infection with Mycobacterium tuberculosis
R-HSA-9824439	Bacterial Infection Pathways
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 235 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, VALK_AML_WITH_FLT3_ITD, WALLACE_PROSTATE_CANCER_RACE_UP, MCLACHLAN_DENTAL_CARIES_UP, SWEET_KRAS_ONCOGENIC_SIGNATURE, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_INTERLEUKIN_4, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, MODULE_64, GOCC_CELL_SURFACE, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (6): receptor-mediated endocytosis (GO:0006898), cellular response to lipopolysaccharide (GO:0071222), cellular response to type II interferon (GO:0071346), cellular response to interleukin-4 (GO:0071353), endocytosis (GO:0006897), symbiont entry into host cell (GO:0046718)

GO Molecular Function (7): virus receptor activity (GO:0001618), transmembrane signaling receptor activity (GO:0004888), D-mannose binding (GO:0005537), signaling receptor activity (GO:0038023), cargo receptor activity (GO:0038024), protein binding (GO:0005515), carbohydrate binding (GO:0030246)

GO Cellular Component (5): plasma membrane (GO:0005886), cell surface (GO:0009986), endosome membrane (GO:0010008), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Antigen processing-Cross presentation	1
Infection with Mycobacterium tuberculosis	1
Dengue Virus Infection	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Disease	1
Bacterial Infection Pathways	1
Infectious disease	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular response to cytokine stimulus	2
vesicle-mediated transport	2
binding	2
cellular anatomical structure	2
endocytosis	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
response to type II interferon	1
response to interleukin-4	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
viral life cycle	1
symbiont entry into host	1
symbiont entry into host cell	1
exogenous protein binding	1
signaling receptor activity	1
monosaccharide binding	1
molecular transducer activity	1
molecular_function	1
molecular adaptor activity	1
membrane	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

2794 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRC1	WDHD1	O75717	976
MRC1	MCM10	Q7L590	964
MRC1	CDC45	O75419	958
MRC1	ITGAM	P11215	924
MRC1	TIPIN	Q9BVW5	911
MRC1	CD163	Q86VB7	883
MRC1	ARG1	P05089	877
MRC1	IL4	P05112	874
MRC1	TIMELESS	Q9UNS1	874
MRC1	CD68	P34810	870
MRC1	CD86	P42081	846
MRC1	IL10	P22301	843
MRC1	IL13	P35225	840
MRC1	CD44	P16070	827
MRC1	CCL2	P13500	819

IntAct

6 interactions, top by confidence:

A	B	Type	Score
MRC1	PTPRC	psi-mi:“MI:0407”(direct interaction)	0.440
MRC1	HSPA5	psi-mi:“MI:0915”(physical association)	0.400
MRC1	HNRNPCL2	psi-mi:“MI:0915”(physical association)	0.400
rpoB	MRC1	psi-mi:“MI:0915”(physical association)	0.000
MRC1	flhA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): MRC1 (Reconstituted Complex), MRC1 (Proximity Label-MS), MRC1 (Proximity Label-MS), MRC1 (Cross-Linking-MS (XL-MS)), AARS (Cross-Linking-MS (XL-MS)), ZNF697 (Cross-Linking-MS (XL-MS)), MRC1 (Affinity Capture-MS)

ESM2 similar proteins: A1A4K5, A2ARA8, A8MWY0, B7ZSK1, O08859, O14638, O15041, O42237, O54890, O70309, P03994, P05106, P07354, P10859, P10915, P15396, P18084, P22413, P22897, P26009, P35436, P48740, P53708, P55252, P70207, P70275, P80747, P98064, P98066, Q00959, Q13224, Q13822, Q28381, Q3UZV7, Q5R1P3, Q5R5M5, Q61830, Q64610, Q6BEA0, Q6P9A2

Diamond homologs: A5PMY6, A6QP79, D3ZWT9, O14594, P02706, P02707, P05451, P06734, P07306, P07307, P07897, P07898, P08290, P08661, P10716, P10758, P11226, P13608, P13611, P16112, P19999, P20693, P22897, P24721, P34927, P41317, P43137, P48304, P49300, P49301, P55066, P55067, P60883, P70194, P81282, P82596, P86854, Q28343, Q28670, Q29011

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
STAT6	“up-regulates quantity by expression”	MRC1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

4358 predictions. Top by Δscore:

Variant	Effect	Δscore
10:17833673:A:AG	acceptor_gain	1.0000
10:17833674:G:GG	acceptor_gain	1.0000
10:17833674:GTT:G	acceptor_gain	1.0000
10:17833836:ACAGG:A	donor_loss	1.0000
10:17833838:AGGTA:A	donor_loss	1.0000
10:17833839:GGTAA:G	donor_loss	1.0000
10:17833840:GTAAG:G	donor_loss	1.0000
10:17833841:T:G	donor_loss	1.0000
10:17849577:A:AG	acceptor_gain	1.0000
10:17849578:G:GG	acceptor_gain	1.0000
10:17849578:GAAA:G	acceptor_gain	1.0000
10:17852964:TA:T	acceptor_loss	1.0000
10:17852964:TAGA:T	acceptor_loss	1.0000
10:17852965:A:AC	acceptor_loss	1.0000
10:17852965:A:AG	acceptor_gain	1.0000
10:17852966:G:GA	acceptor_gain	1.0000
10:17852966:GA:G	acceptor_gain	1.0000
10:17852966:GAGCC:G	acceptor_gain	1.0000
10:17853120:GCAAG:G	donor_gain	1.0000
10:17853121:CAAGG:C	donor_loss	1.0000
10:17853122:AAGG:A	donor_loss	1.0000
10:17853123:AGGT:A	donor_loss	1.0000
10:17853123:AGGTA:A	donor_loss	1.0000
10:17853124:GG:G	donor_loss	1.0000
10:17853125:G:A	donor_loss	1.0000
10:17853125:G:GG	donor_gain	1.0000
10:17853125:GTAAG:G	donor_loss	1.0000
10:17853126:T:A	donor_loss	1.0000
10:17853126:T:G	donor_loss	1.0000
10:17856230:T:A	acceptor_gain	1.0000

AlphaMissense

9678 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:17823312:G:C	W100C	0.999
10:17823312:G:T	W100C	0.999
10:17875185:T:A	C828S	0.999
10:17875186:G:C	C828S	0.999
10:17875187:C:G	C828W	0.999
10:17879757:G:C	W885C	0.999
10:17879757:G:T	W885C	0.999
10:17880530:T:A	W909R	0.999
10:17880530:T:C	W909R	0.999
10:17885387:G:C	W1033C	0.999
10:17885387:G:T	W1033C	0.999
10:17894258:T:A	W1066R	0.999
10:17894258:T:C	W1066R	0.999
10:17894260:G:C	W1066C	0.999
10:17894260:G:T	W1066C	0.999
10:17900841:G:C	W1179C	0.999
10:17900841:G:T	W1179C	0.999
10:17823115:T:A	C35S	0.998
10:17823116:G:C	C35S	0.998
10:17823192:G:C	W60C	0.998
10:17823192:G:T	W60C	0.998
10:17823310:T:A	W100R	0.998
10:17823310:T:C	W100R	0.998
10:17823427:T:A	W139R	0.998
10:17823427:T:C	W139R	0.998
10:17823429:G:C	W139C	0.998
10:17823429:G:T	W139C	0.998
10:17827658:T:A	C194S	0.998
10:17827658:T:C	C194R	0.998
10:17827659:G:C	C194S	0.998

dbSNP variants (sampled 300 via entrez): RS1000021646 (10:17825121 C>G,T), RS1000023384 (10:17864656 C>A,T), RS1000047075 (10:17879569 G>A,T), RS1000121320 (10:17910096 G>C), RS1000128497 (10:17904504 G>A,C), RS1000130327 (10:17829939 A>T), RS1000175112 (10:17834458 A>G), RS1000176615 (10:17820200 G>A), RS1000220725 (10:17848614 C>G), RS1000221288 (10:17910324 T>C), RS1000226079 (10:17834259 G>T), RS1000238649 (10:17819673 T>C), RS1000330271 (10:17891511 A>C), RS1000337465 (10:17874983 G>A,T), RS1000395710 (10:17904231 C>T)

Disease associations

OMIM: gene MIM:153618 | disease phenotypes: MIM:609888

GenCC curated gene-disease

Mondo (1): leprosy, susceptibility to, 1 (MONDO:0012358)

Orphanet (1): Leprosy (Orphanet:548)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000583_17	Hematological and biochemical traits	1.000000e-16
GCST001247_3	Cardiovascular disease risk factors	3.000000e-10
GCST002540_2	Osteoarthritis biomarkers	2.000000e-12
GCST002986_4	Childhood and early adolescence aggressive behavior	2.000000e-06
GCST005999_25	Aspartate aminotransferase levels	2.000000e-19
GCST006585_662	Blood protein levels	1.000000e-06
GCST011351_15	Aspartate aminotransferase levels	2.000000e-42

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004736	aspartate aminotransferase measurement
EFO:0005890	osteoarthritis biomarker measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2176854 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
cyclopamine	increases expression	1
2,4,6-tribromophenol	increases expression	1
decabromobiphenyl ether	increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
mono-(2-ethylhexyl)phthalate	affects cotreatment, decreases expression	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	increases expression	1
monobutyl phthalate	affects cotreatment, decreases expression	1
amyloid beta-protein (25-35)	affects cotreatment, decreases expression	1
amyloid beta-protein (1-40)	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
mono-benzyl phthalate	affects cotreatment, decreases expression	1
bardoxolone methyl	decreases reaction, increases expression	1
lipopolysaccharide, E coli O55-B5	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
Valsartan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Bosentan	affects expression	1
Vehicle Emissions	increases expression	1
Benzo(a)pyrene	decreases expression	1
Chenodeoxycholic Acid	decreases expression, affects cotreatment	1
Copper	affects cotreatment, increases expression	1
Deoxycholic Acid	affects cotreatment, decreases expression	1
Dietary Fats	increases expression, increases reaction	1
Endosulfan	decreases expression, decreases reaction	1
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2185429	Binding	Displacement of biotinylated-TM PAA from human MMR after 3 hrs by colorimetry	Target Selectivity of FimH Antagonists. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8KR	Abcam HCT 116 MRC1 KO	Cancer cell line	Male
CVCL_B9MZ	Abcam A-549 MRC1 KO	Cancer cell line	Male
CVCL_F1PA	HyCyte HEK293 KO-hMRC1	Transformed cell line	Female

Clinical trials (associated diseases)

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