CD163

Summary

CD163 (CD163 molecule, HGNC:1631) is a protein-coding gene on chromosome 12p13.31, encoding Scavenger receptor cysteine-rich type 1 protein M130 (Q86VB7). Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage.

The protein encoded by this gene is a member of the scavenger receptor cysteine-rich (SRCR) superfamily, and is exclusively expressed in monocytes and macrophages. It functions as an acute phase-regulated receptor involved in the clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages, and may thereby protect tissues from free hemoglobin-mediated oxidative damage. This protein may also function as an innate immune sensor for bacteria and inducer of local inflammation. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 9332 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 143 total
• MANE Select transcript: NM_203416

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1631
Approved symbol	CD163
Name	CD163 molecule
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	M130, MM130, SCARI1
Ensembl gene	ENSG00000177575
Ensembl biotype	protein_coding
OMIM	605545
Entrez	9332

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 17 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000359156, ENST00000396620, ENST00000432237, ENST00000534848, ENST00000537044, ENST00000537626, ENST00000538840, ENST00000539632, ENST00000541972, ENST00000542280, ENST00000542705, ENST00000894017, ENST00000894018, ENST00000894019, ENST00000960361, ENST00000960362, ENST00000960363, ENST00000960364, ENST00000960365, ENST00000960366, ENST00000960367, ENST00000960368

RefSeq mRNA: 4 — MANE Select: NM_203416 NM_001370145, NM_001370146, NM_004244, NM_203416

CCDS: CCDS53742, CCDS8578

Canonical transcript exons

ENST00000432237 — 17 exons

Exon	Start	End
ENSE00001409726	7481161	7481256
ENSE00001525724	7479860	7479913
ENSE00003489825	7496813	7497133
ENSE00003509905	7495081	7495401
ENSE00003527310	7487359	7487673
ENSE00003533295	7486894	7486986
ENSE00003563492	7498868	7499188
ENSE00003593040	7483367	7483675
ENSE00003614162	7482966	7483004
ENSE00003618294	7486499	7486813
ENSE00003642268	7487773	7488087
ENSE00003648052	7482643	7482762
ENSE00003654003	7501139	7501462
ENSE00003661406	7502478	7502564
ENSE00003667488	7485096	7485416
ENSE00003905675	7503645	7503777
ENSE00003905715	7470811	7471397

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 99.00.

FANTOM5 (CAGE): breadth broad, TPM avg 21.9178 / max 4546.1519, expressed in 397 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129271	19.3922	390
129270	1.8922	250
206564	0.2334	93
206566	0.1639	81
206565	0.0813	51
206563	0.0665	32
129268	0.0500	19
129269	0.0383	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	99.00	gold quality
mucosa of stomach	UBERON:0001199	98.68	gold quality
lower lobe of lung	UBERON:0008949	98.46	gold quality
right adrenal gland cortex	UBERON:0035827	98.40	gold quality
right adrenal gland	UBERON:0001233	98.19	gold quality
spleen	UBERON:0002106	97.98	gold quality
left adrenal gland cortex	UBERON:0035825	97.66	gold quality
left adrenal gland	UBERON:0001234	97.65	gold quality
monocyte	CL:0000576	97.60	gold quality
left uterine tube	UBERON:0001303	97.44	gold quality
mononuclear cell	CL:0000842	97.42	gold quality
right coronary artery	UBERON:0001625	97.39	gold quality
leukocyte	CL:0000738	97.26	gold quality
pericardium	UBERON:0002407	97.09	gold quality
upper lobe of lung	UBERON:0008948	96.75	gold quality
upper lobe of left lung	UBERON:0008952	96.64	gold quality
left coronary artery	UBERON:0001626	96.52	gold quality
adrenal cortex	UBERON:0001235	96.36	gold quality
descending thoracic aorta	UBERON:0002345	96.28	gold quality
omental fat pad	UBERON:0010414	96.11	gold quality
peritoneum	UBERON:0002358	96.03	gold quality
decidua	UBERON:0002450	95.89	gold quality
heart right ventricle	UBERON:0002080	95.68	gold quality
adrenal gland	UBERON:0002369	95.50	gold quality
coronary artery	UBERON:0001621	95.41	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.33	gold quality
thoracic aorta	UBERON:0001515	95.27	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.16	gold quality
gall bladder	UBERON:0002110	95.13	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	3838.27
E-GEOD-134144	yes	2338.81
E-GEOD-135922	yes	2259.05
E-GEOD-84465	yes	2009.81
E-MTAB-8495	yes	1973.61
E-HCAD-36	yes	1558.70
E-MTAB-10553	yes	1344.49
E-HCAD-15	yes	1263.22
E-GEOD-149689	yes	1114.21
E-MTAB-8530	yes	800.20
E-HCAD-24	yes	397.30
E-HCAD-1	yes	77.68
E-CURD-122	yes	67.29
E-MTAB-8142	yes	53.82
E-MTAB-6701	yes	49.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, ETS2, SP1, SPI1

miRNA regulators (miRDB)

63 targeting CD163, 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-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514

Literature-anchored findings (GeneRIF, showing 40)

• soluble CD163 inhibits phorbol ester-induced lymphocyte proliferation (PMID:11688984)
• haptoglobin-dependent HbSR/CD163 scavenging system for hemoglobin clearance prevents toxic effects of hemoglobin in plasma and kidney (PMID:11865982)
• has at least two distinct functions: the clearance of hemoglobin in its cell-bound form and participation in anti-inflammation as a soluble factor, exhibiting cytokine-like functions (PMID:12208511)
• a metalloproteinase is responsible for LPS-mediated shedding of CD163 (PMID:12377940)
• CD163 mediates an anti-inflammatory pathway involving interleukin-10 release and heme oxygenase-1 synthesis. (PMID:14656926)
• sCD163 may be a valuable laboratory parameter in monitoring diseases such as Gaucher. (PMID:14962251)
• Increased numbers of CD163+ macrophages in SpA synovium and local production of sCD163 are associated with global inflammation as well as impairment of T cell activation, suggesting a dual role for CD163+ macrophages in Spondylarthropathy synovitis. (PMID:15146432)
• SRCR domain 3 of CD163 is an exposed domain and a critical determinant for the calcium-sensitive coupling of haptoglobin.hemoglobin complexes (PMID:15448162)
• sCD163-NMMHCA complexes were present in activated T lymphocytes after incubation with shed sCD163 (PMID:15479433)
• Serum levels of soluble CD163 were highly increased in reactive hemophagocytic syndrome, suggesting a macrophage-specific marker. (PMID:15613100)
• in HIV encephalitis, expression of CD163 was far more widespread in grey matter ramified microglia than was expression of HLA-DR (PMID:15624762)
• CD163 specifically reveals perivascular macrophages(PVM) in the normal human CNS. In MS lesions, CD163 staining reveals expression on foamy macrophages and microglia, besides an upregulation of the amount of PVM stained. (PMID:15846794)
• results identify CD163 as a scavenger receptor for native Hb and small-molecular-weight Hb-based blood substitutes after Hp depletion (PMID:16189277)
• CD163 identifies perivascular macrophages in normal and viral encephalitic brains and potential precursors to perivascular macrophages in blood. (PMID:16507898)
• AM-3K, an anti-macrophage antibody, recognizes CD163, a molecule associated with an anti-inflammatory macrophage phenotype. (PMID:16517975)
• These data suggest that hemoglobin may mediate a stimulatory effect on erythropoiesis through the activation of CD163 on hematopoietic progenitor cells. (PMID:16522161)
• symptomatic plaques show a more pronounced induction of CD163 and HO-1 in response to plaque hemorrhages. (PMID:17095719)
• only the beta-chain of haptoglobin is involved in CD163 receptor recognition (PMID:17102136)
• The increased free-hemoblobin, haptoglobin, and sCD163 in chronic renal failure suggested 8-isoprostane-mediated suppression of Hb catabolism through CD163 receptor shedding (PMID:17117055)
• CD163-mediated Hb-Hp uptake by peripheral blood monocytes constitutes an Hb-Hp clearance pathway, which acts at the site of intravascular hemolysis to reduce Hb-Hp circulation time and toxicity (PMID:17460152)
• Individuals with diabetes mellitus and a haptoglobin 2.2 genotype demonstrate lower CD163 scavenger receptor levels and an impaired hemoglobin clearance capacity, with increased incidence of myocardial infarction. (PMID:17525367)
• CD163 either acts as a TWEAK scavenger in pathological conditions or serves as an alternate receptor for TWEAK in cells lacking Fn14/TweakR. (PMID:17548657)
• Activated macrophages are involved in ALF resulting in a 10-fold increase in sCD163. A high level (>26mg/l) of sCD163 was significantly correlated with fatal outcome and might be used with other parameters to determine prognosis. (PMID:17629586)
• CD163 and HCP-1 constitute a linked pathway for Hb catabolism and heme-iron recycling in human macrophages. (PMID:17947394)
• DC-sign+ CD163+ macrophages expressing hyaluronan receptor LYVE-1 are located within chorion villi of the placenta. (PMID:18078989)
• CD163, a marker of perivascular macrophages, is up-regulated by microglia in simian immunodeficiency virus encephalitis after haptoglobin-hemoglobin complex stimulation and is suggestive of breakdown of the blood-brain barrier. (PMID:18276779)
• High-level expression of CD163 is associated with leiomyosarcomas (PMID:18316565)
• Data show that in cardiac surgical patients the expression of scavenger molecule CD163 on monocytes is significantly higher in “on-pump” patients than that of “off-pump” patients. (PMID:18320015)
• studied gene expression profile of brain lesions of a patient with Neuromyelitis optica by using DNA microarray; found marked up-regulation of interferon gamma-inducible protein 30 (IFI30), CD163, and secreted phosphoprotein 1 (SPP1, osteopontin) (PMID:18410276)
• Helpful for evaluation of a monocytic component in acute myeloid leukemias. (PMID:18542032)
• Casein kinase II activity is increased by the binding of haptoglobin 1-1-hemoglobin to CD163. (PMID:18563533)
• Data show that CD64 indexes for neutrophils and monocytes, and CD163 index for neutrophils can all be used for discrimination of SIRS and sepsis in critically ill neonates and children. (PMID:18604302)
• during bacterial infection, CD163 on resident tissue macrophages acts as an innate immune sensor and inducer of local inflammation (PMID:18849484)
• CD163 is a useful adjunct in distinguishing AFX from other malignant cutaneous spindle cell tumors and offers improved specificity in identifying cutaneous histiocytic/dendritic lesions. (PMID:19040468)
• CD163 is of diagnostic value in cutaneous spindle cell lesions. (PMID:19040468)
• Hp protects hemoglobin (Hb) when oxidatively challenged with H(2)O(2) preserving CD163-mediated Hb clearance under oxidative stress conditions. (PMID:19131549)
• The CD163-expressing macrophages recognize and internalize TWEAK: potential consequences in atherosclerosis. (PMID:19473660)
• Results show that both serum levels of sCD163 and the presence of CD68(+) macrophage infiltration at the tumor invasive front are independent predictors of survival in AJCC stage I/II melanoma. (PMID:19528371)
• High CD163 expression is associated with rectal cancer. (PMID:19582880)
• findings show that CD163 only interacts with porcine reproductive and respiratory syndrome virus (PRRSV) in early endosomes (PMID:19885719)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd163	ENSMUSG00000008845
rattus_norvegicus	Cd163	ENSRNOG00000010253

Paralogs (15): CD6 (ENSG00000013725), CD5L (ENSG00000073754), LGALS3BP (ENSG00000108679), CD5 (ENSG00000110448), LOX (ENSG00000113083), LOXL3 (ENSG00000115318), LOXL1 (ENSG00000129038), LOXL2 (ENSG00000134013), LOXL4 (ENSG00000138131), SSC4D (ENSG00000146700), PRSS12 (ENSG00000164099), CD163L1 (ENSG00000177675), SSC5D (ENSG00000179954), DMBT1 (ENSG00000187908), SCART1 (ENSG00000214279)

Protein

Protein identifiers

Scavenger receptor cysteine-rich type 1 protein M130 — Q86VB7 (reviewed: Q86VB7)

Alternative names: Hemoglobin scavenger receptor

All UniProt accessions (5): C9JHR8, Q86VB7, F5GZZ9, H0YFM0, H0YGZ7

UniProt curated annotations — full annotation on UniProt →

Function. Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. May play a role in the uptake and recycling of iron, via endocytosis of hemoglobin/haptoglobin and subsequent breakdown of heme. Binds hemoglobin/haptoglobin complexes in a calcium-dependent and pH-dependent manner. Exhibits a higher affinity for complexes of hemoglobin and multimeric haptoglobin of HP1F phenotype than for complexes of hemoglobin and dimeric haptoglobin of HP1S phenotype. Induces a cascade of intracellular signals that involves tyrosine kinase-dependent calcium mobilization, inositol triphosphate production and secretion of IL6 and CSF1. Isoform 3 exhibits the higher capacity for ligand endocytosis and the more pronounced surface expression when expressed in cells. After shedding, the soluble form (sCD163) may play an anti-inflammatory role, and may be a valuable diagnostic parameter for monitoring macrophage activation in inflammatory conditions.

Subunit / interactions. Interacts with CSNK2B.

Subcellular location. Secreted Cell membrane.

Tissue specificity. Expressed in monocytes and mature macrophages such as Kupffer cells in the liver, red pulp macrophages in the spleen, cortical macrophages in the thymus, resident bone marrow macrophages and meningeal macrophages of the central nervous system. Expressed also in blood. Isoform 1 is the lowest abundant in the blood. Isoform 2 is the lowest abundant in the liver and the spleen. Isoform 3 is the predominant isoform detected in the blood.

Post-translational modifications. A soluble form (sCD163) is produced by proteolytic shedding which can be induced by lipopolysaccharide, phorbol ester and Fc region of immunoglobulin gamma. This cleavage is dependent on protein kinase C and tyrosine kinases and can be blocked by protease inhibitors. The shedding is inhibited by the tissue inhibitor of metalloproteinase TIMP3, and thus probably induced by membrane-bound metalloproteinases ADAMs. Phosphorylated.

Domain organisation. The SRCR domain 3 mediates calcium-sensitive interaction with hemoglobin/haptoglobin complexes.

Induction. Induced by anti-inflammatory mediators such as glucocorticoids, interleukin-6/IL6 and interleukin-10/IL10; suppressed by pro-inflammatory mediators like bacterial lipopolysaccharides (LPS), IFNG/IFN-gamma and TNF.

Miscellaneous. Intravenous lipopolysaccharide (LPS) produces a rapid rise of sCD163 in plasma of patient as it induces metalloproteinase-mediated shedding from monocytes surface. Long-term LPS infusion finally increases expression of the membrane-bound form on circulating monocytes. The soluble form (sCD163) in plasma is a novel parameter in diseases affecting macrophage function and monocyte/macrophage load in the body. The concentration of sCD163 is probably reflecting the number of macrophages of the ‘alternative macrophage activation’ phenotype with a high CD163 expression playing a major role in dampening the inflammatory response and scavenging components of damaged cells. This has initiated a number of clinical studies for evaluation of sCD163 as a disease marker in inflammatory conditions e.g. infection, autoimmune disease, transplantation, atherosclerosis and cancer.

Isoforms (4)

UniProt ID	Names	Canonical?
Q86VB7-1	1, Long tail variant 1	yes
Q86VB7-2	2, Long tail variant 2
Q86VB7-3	3, Short tail variant
Q86VB7-4	4

RefSeq proteins (4): NP_001357074, NP_001357075, NP_004235, NP_981961* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001190	SRCR	Domain
IPR036772	SRCR-like_dom_sf	Homologous_superfamily

Pfam: PF00530

UniProt features (136 total): strand 56, disulfide bond 26, helix 19, domain 9, turn 4, site 4, glycosylation site 4, splice variant 3, mutagenesis site 3, chain 2, topological domain 2, signal peptide 1, short sequence motif 1, transmembrane region 1, sequence variant 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
9TQD	ELECTRON MICROSCOPY	2.8
9HEJ	ELECTRON MICROSCOPY	2.82
8XMW	ELECTRON MICROSCOPY	2.94
9NB5	ELECTRON MICROSCOPY	3
8XMK	ELECTRON MICROSCOPY	3.03
9HEL	ELECTRON MICROSCOPY	3.1
8XMP	ELECTRON MICROSCOPY	3.11
9HEK	ELECTRON MICROSCOPY	3.15
8XMQ	ELECTRON MICROSCOPY	3.21
9NB6	ELECTRON MICROSCOPY	3.3
9FHB	ELECTRON MICROSCOPY	3.87
9NB8	ELECTRON MICROSCOPY	4
9FMU	ELECTRON MICROSCOPY	4.46
9FNO	ELECTRON MICROSCOPY	5.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VB7-F1	77.72	0.29

Functional residue map

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

Catalytic / active sites (4): 269–270 (cleavage; in calcium-free condition); 281–282 (cleavage; in calcium-free condition); 333–334 (cleavage; in calcium-free condition); 360–361 (cleavage; in calcium-free condition)

Disulfide bonds (26): 76–141, 89–151, 120–130, 184–248, 197–258, 228–238, 291–355, 304–365, 335–345, 398–462, 411–472, 442–452, 503–567, 516–577, 547–557, 608–672, 621–682, 652–662, 744–808, 757–818 …

Glycosylation sites (4): 105, 140, 767, 1027

Mutagenesis-validated functional residues (3):

Position	Phenotype
1072	impaired phosphorylation by prkca.
1084	impaired phosphorylation by prkca.
1096	massive decrease of endocytotic activity.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-2168880	Scavenging of heme from plasma
R-HSA-9662834	CD163 mediating an anti-inflammatory response
R-HSA-1643685	Disease
R-HSA-2173782	Binding and Uptake of Ligands by Scavenger Receptors
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5663205	Infectious disease
R-HSA-9658195	Leishmania infection
R-HSA-9662851	Anti-inflammatory response favouring Leishmania parasite infection
R-HSA-9664433	Leishmania parasite growth and survival
R-HSA-9824443	Parasitic Infection Pathways

MSigDB gene sets: 263 (showing top): MCLACHLAN_DENTAL_CARIES_UP, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, MODULE_64, MODULE_317, GOCC_CELL_SURFACE, GOBP_VESICLE_MEDIATED_TRANSPORT, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, MARTINEZ_RB1_TARGETS_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, BLALOCK_ALZHEIMERS_DISEASE_UP, MODULE_88, DODD_NASOPHARYNGEAL_CARCINOMA_UP, PTF1BETA_Q6

GO Biological Process (3): acute-phase response (GO:0006953), inflammatory response (GO:0006954), vesicle-mediated transport (GO:0016192)

GO Molecular Function (3): scavenger receptor activity (GO:0005044), scaffold protein binding (GO:0097110), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), cytosol (GO:0005829), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), endocytic vesicle membrane (GO:0030666), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Binding and Uptake of Ligands by Scavenger Receptors	1
Anti-inflammatory response favouring Leishmania parasite infection	1
Vesicle-mediated transport	1
Disease	1
Parasitic Infection Pathways	1
Leishmania parasite growth and survival	1
Leishmania infection	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
acute inflammatory response	1
defense response	1
transport	1
cellular process	1
cargo receptor activity	1
protein binding	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
endocytic vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD163	HP	P00737	999
CD163	CD36	P16671	976
CD163	GP2	P55259	974
CD163	HPX	P02790	927
CD163	CD68	P34810	903
CD163	MRC1	P22897	883
CD163	IL6	P05231	855
CD163	HPR	P00739	845
CD163	IL1B	P01584	820
CD163	IL10	P22301	814
CD163	PTPRC	P08575	807
CD163	CCR2	P41597	799
CD163	SIGLEC1	Q9BZZ2	798
CD163	CD86	P42081	794
CD163	FOXP3	Q9BZS1	789

IntAct

7 interactions, top by confidence:

A	B	Type	Score
FCGR1A	CD163	psi-mi:“MI:0915”(physical association)	0.560
CD163	HOXA1	psi-mi:“MI:0915”(physical association)	0.370
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
CD163	FCGR1A	psi-mi:“MI:0915”(physical association)	0.000
CD163	uup	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): CD163 (Two-hybrid), CD163 (Affinity Capture-MS), CD163 (Two-hybrid), CSNK2B (Two-hybrid), CSNK2B (Reconstituted Complex), CSNK2B (Affinity Capture-Western), CD163 (Affinity Capture-MS), CD163 (Affinity Capture-MS), CD163 (Protein-peptide), CD163 (Affinity Capture-MS)

ESM2 similar proteins: A1L0T3, A1L4H1, D3ZTE0, G3V801, O08762, O43866, O75636, O95428, O97507, P00748, P22457, P56730, P58215, P69525, P69526, P85521, P98140, Q02853, Q04756, Q04962, Q24K22, Q2VL90, Q2VLG4, Q2VLG6, Q2VLH6, Q499S5, Q4G0T1, Q5G265, Q5G268, Q5G269, Q5G270, Q5G271, Q5IJ48, Q6QNF4, Q70UZ7, Q769J6, Q76LX8, Q7Z410, Q80YA8, Q80YC5

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

5 interactions.

A	Effect	B	Mechanism
PRKCA	unknown	CD163	phosphorylation
HBB	“up-regulates activity”	CD163	binding
HBA1	“up-regulates activity”	CD163	binding
CD163	“down-regulates quantity by destabilization”	hb:hp	binding
CSNK2B	“up-regulates activity”	CD163	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	107
Likely benign	9
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

2238 predictions. Top by Δscore:

Variant	Effect	Δscore
12:7481257:C:CC	acceptor_gain	1.0000
12:7483005:C:CC	acceptor_gain	1.0000
12:7486494:TTTA:T	donor_loss	1.0000
12:7486495:TTA:T	donor_loss	1.0000
12:7486496:TACC:T	donor_loss	1.0000
12:7486497:AC:A	donor_loss	1.0000
12:7486498:CC:C	donor_loss	1.0000
12:7486810:CTCT:C	acceptor_gain	1.0000
12:7486812:CT:C	acceptor_gain	1.0000
12:7486814:C:CC	acceptor_gain	1.0000
12:7486814:CTG:C	acceptor_loss	1.0000
12:7487952:AATTC:A	donor_gain	1.0000
12:7487956:C:CA	donor_gain	1.0000
12:7487979:T:TA	donor_gain	1.0000
12:7498866:A:AC	donor_gain	1.0000
12:7498867:C:CC	donor_gain	1.0000
12:7501133:TCTTA:T	donor_loss	1.0000
12:7501134:CTTA:C	donor_loss	1.0000
12:7501135:TTA:T	donor_loss	1.0000
12:7501136:TAC:T	donor_loss	1.0000
12:7501137:A:T	donor_loss	1.0000
12:7502470:GTACT:G	donor_loss	1.0000
12:7502472:ACTC:A	donor_loss	1.0000
12:7502473:CTC:C	donor_loss	1.0000
12:7502474:TCA:T	donor_loss	1.0000
12:7502475:CA:C	donor_loss	1.0000
12:7502476:A:AC	donor_gain	1.0000
12:7502476:A:T	donor_loss	1.0000
12:7502476:AC:A	donor_gain	1.0000
12:7502477:C:A	donor_loss	1.0000

AlphaMissense

7327 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:7483581:C:A	W958C	0.998
12:7483581:C:G	W958C	0.998
12:7483462:C:G	C998S	0.996
12:7483463:A:T	C998S	0.996
12:7483583:A:G	W958R	0.996
12:7483583:A:T	W958R	0.996
12:7486713:C:A	W748C	0.996
12:7486713:C:G	W748C	0.996
12:7497027:C:A	W295C	0.996
12:7497027:C:G	W295C	0.996
12:7499106:C:A	W180C	0.996
12:7499106:C:G	W180C	0.996
12:7497029:A:G	W295R	0.995
12:7497029:A:T	W295R	0.995
12:7483555:C:G	C967S	0.994
12:7483556:A:T	C967S	0.994
12:7497040:C:T	C291Y	0.994
12:7499095:C:G	C184S	0.994
12:7499095:C:T	C184Y	0.994
12:7499096:A:T	C184S	0.994
12:7483372:C:G	C1028S	0.993
12:7483373:A:T	C1028S	0.993
12:7483554:A:C	C967W	0.993
12:7496862:C:A	W350C	0.993
12:7496862:C:G	W350C	0.993
12:7496878:C:G	C345S	0.993
12:7496879:A:T	C345S	0.993
12:7497051:C:A	W287C	0.993
12:7497051:C:G	W287C	0.993
12:7498873:C:G	C258S	0.993

dbSNP variants (sampled 300 via entrez): RS1000023282 (12:7475632 A>C), RS1000101139 (12:7493916 G>A), RS1000165232 (12:7504119 A>G), RS1000234025 (12:7473578 T>A,C), RS1000277112 (12:7503873 C>T), RS1000286403 (12:7473157 T>C), RS1000384620 (12:7504420 A>G), RS1000391942 (12:7480684 C>T), RS1000447820 (12:7496205 C>T), RS1000701846 (12:7495911 G>A,C), RS1000715321 (12:7502926 T>A), RS1000846109 (12:7480327 C>A), RS1001043447 (12:7494341 G>T), RS1001129297 (12:7481418 T>C), RS1001337455 (12:7489510 A>G)

Disease associations

OMIM: gene MIM:605545 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): lung adenocarcinoma (MONDO:0005061), squamous cell carcinoma (MONDO:0005096)

Orphanet (1): NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000583_22	Hematological and biochemical traits	3.000000e-26
GCST004232_36	HDL cholesterol levels	7.000000e-09
GCST004232_90	HDL cholesterol levels	1.000000e-08
GCST004234_18	HDL cholesterol levels	5.000000e-06
GCST006014_35	Creatine kinase levels	4.000000e-273
GCST009151_11	High density lipoprotein cholesterol levels	3.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004534	creatine kinase measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression, affects cotreatment, increases abundance	3
bisphenol A	affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
GSK-J4	increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
arsenite	increases methylation	1
sodium bichromate	decreases expression	1
mono-(2-ethylhexyl)phthalate	affects cotreatment, decreases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
monobutyl phthalate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
mono-benzyl phthalate	affects cotreatment, decreases expression	1
bardoxolone methyl	decreases reaction, increases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
Valsartan	decreases expression	1
Air Pollutants	affects methylation, increases abundance	1
Calcitriol	decreases expression	1
Choline	affects expression	1
Chromium	affects cotreatment, increases abundance, increases expression	1
Cobalt	affects cotreatment, increases abundance, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Disulfiram	decreases expression, affects cotreatment	1
Indomethacin	affects cotreatment, decreases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Magnesium	affects cotreatment, increases abundance, increases expression	1

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8CU	Abcam HCT 116 CD163 KO	Cancer cell line	Male
CVCL_B9F2	Abcam A-549 CD163 KO	Cancer cell line	Male
CVCL_C0Z7	FK-A6	Spontaneously immortalized cell line	Sex unspecified
CVCL_D7M0	Ubigene A-549 CD163 KO	Cancer cell line	Male
CVCL_D9BF	Ubigene HEK293 CD163 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02399566	PHASE4	UNKNOWN	Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma
NCT02804646	PHASE4	UNKNOWN	Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma
NCT00868088	PHASE4	COMPLETED	Photodynamic Therapy to Treat Actinic Damage in Patients With Squamous Cell Carcinoma (SCC) of the Lip
NCT02088515	PHASE4	COMPLETED	Nedaplatin (Jiebaishu®) Combined With Docetaxel for Advanced Lung Squamous Cell Carcinoma
NCT02151149	PHASE4	COMPLETED	Safety and Efficacy Study of Abraxane in Combination With Carboplatin to Treat Advanced NSCL Cancer in the Elderly
NCT03388931	PHASE4	WITHDRAWN	Radiotherapy Dose Escalation in Locally Advanced Squamous Cell Carcinoma of the Larynx or Hypopharynx
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01798485	PHASE3	TERMINATED	A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
NCT02011997	PHASE3	UNKNOWN	Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
NCT03676192	PHASE3	COMPLETED	To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer
NCT04339218	PHASE3	RECRUITING	Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma
NCT05204758	PHASE3	COMPLETED	Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect
NCT05717803	PHASE3	RECRUITING	Segmentectomy for Ground Glass-dominant Invasive Lung Cancer (ECTOP-1012)
NCT05943795	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
NCT06031181	PHASE3	RECRUITING	Sublobar Resection for Adenocarcinoma in Situ/Minimally Invasive Adenocarcinoma Diagnosed by Intraoperative Frozen Section (ECTOP-1019)
NCT06031246	PHASE3	RECRUITING	Selective Lymph Node Dissection for cT1N0M0 Invasive NSCLC With CTR>0.5 Located in the Apical Segment (ECTOP-1018)
NCT06634966	PHASE3	RECRUITING	Segmentectomy for Solid-dominant Lung Cancer
NCT07169903	PHASE3	NOT_YET_RECRUITING	Segmentectomy vs Lobectomy for 2 - 3cm IASLC Grade 1-2 Lung Adenocarcinoma: A Multi-center RCT
NCT07481786	PHASE3	RECRUITING	Bevacizumab Plus FSRT Versus Hippocampus-Avoidant WBRT in Lung Adenocarcinoma With Extensive Brain Metastases
NCT00101582	PHASE3	COMPLETED	Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer
NCT00201279	PHASE3	COMPLETED	Chemoprevention Study of Oral Cavity Squamous Cell Carcinoma
NCT00201383	PHASE3	COMPLETED	Post-Operative Adjuvant Concurrent Chemoradiotherapy For High Risk Oral Cavity Squamous Cell Carcinoma Patients
NCT00382031	PHASE3	COMPLETED	Zalutumumab in Patients With Non-curable Head and Neck Cancer
NCT00472459	PHASE3	COMPLETED	Photodynamic Therapy (PDT) With Metvix® 160 Milligrams/Gram Cream in Organ Transplant Participants With Non-melanoma Skin Cancer
NCT00559351	PHASE3	TERMINATED	RCT on the Combined Modality Treatment of Squamous Cell Carcinoma of the Esophagus
NCT01161498	PHASE3	TERMINATED	Study of Safety and Efficacy of Talimogene Laherparepvec With Cisplatin and Radiotherapy for Treatment of Locally Advanced Head and Neck Cancer
NCT01363466	PHASE3	TERMINATED	Evaluation of Hysterectomy After Chemoradiation Therapy for Stage IB2/II Cervical Cancer
NCT01532453	PHASE3	TERMINATED	Prevention of UV-induced Carcinogenic Skin Alterations in Immunosuppressed Solid Organ Transplanted Patients
NCT01706939	PHASE3	ACTIVE_NOT_RECRUITING	The Quarterback Trial: Reduced Dose Radiotherapy for HPV+ Oropharynx Cancer
NCT03115476	PHASE3	TERMINATED	A Trial to Compare the Incidence of Squamous Cell Carcinoma (SCC) and Other Skin Neoplasia on Skin Areas Treated With Ingenol Disoxate Gel or Vehicle Gel for Actinic Keratosis on Face and Chest or Scalp
NCT03257267	PHASE3	COMPLETED	Study of Cemiplimab in Adults With Cervical Cancer
NCT00040794	PHASE2	COMPLETED	Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer
NCT00087412	PHASE2	COMPLETED	S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer
NCT00118144	PHASE2	COMPLETED	Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer
NCT00118183	PHASE2	COMPLETED	Docetaxel With Either Cetuximab or Bortezomib as First-Line Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer