CD14

Summary

CD14 (CD14 molecule, HGNC:1628) is a protein-coding gene on chromosome 5q31.3, encoding Monocyte differentiation antigen CD14 (P08571). Coreceptor for bacterial lipopolysaccharide.

The protein encoded by this gene is a surface antigen that is preferentially expressed on monocytes/macrophages. It cooperates with other proteins to mediate the innate immune response to bacterial lipopolysaccharide, and to viruses. This gene has been identified as a target candidate in the treatment of SARS-CoV-2-infected patients to potentially lessen or inhibit a severe inflammatory response. Alternative splicing results in multiple transcript variants encoding the same protein.

Source: NCBI Gene 929 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 54 total
• Druggable target: yes
• MANE Select transcript: NM_000591

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1628
Approved symbol	CD14
Name	CD14 molecule
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170458
Ensembl biotype	protein_coding
OMIM	158120
Entrez	929

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000302014, ENST00000498971, ENST00000512545, ENST00000519715, ENST00000905960

RefSeq mRNA: 4 — MANE Select: NM_000591 NM_000591, NM_001040021, NM_001174104, NM_001174105

CCDS: CCDS4232

Canonical transcript exons

ENST00000302014 — 2 exons

Exon	Start	End
ENSE00002058600	140633069	140633175
ENSE00003848313	140631732	140632980

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 99.75.

FANTOM5 (CAGE): breadth broad, TPM avg 40.2215 / max 1789.9405, expressed in 662 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63816	26.0982	567
63817	12.6097	524
63820	0.7860	192
63821	0.3485	126
63815	0.1623	87
63818	0.1215	61
63819	0.0954	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.75	gold quality
mononuclear cell	CL:0000842	99.71	gold quality
leukocyte	CL:0000738	99.68	gold quality
granulocyte	CL:0000094	99.42	gold quality
right lobe of liver	UBERON:0001114	98.67	gold quality
right coronary artery	UBERON:0001625	98.30	gold quality
blood	UBERON:0000178	98.17	gold quality
liver	UBERON:0002107	98.02	gold quality
left adrenal gland	UBERON:0001234	97.94	gold quality
left adrenal gland cortex	UBERON:0035825	97.68	gold quality
right adrenal gland	UBERON:0001233	97.46	gold quality
synovial joint	UBERON:0002217	97.39	gold quality
gall bladder	UBERON:0002110	97.36	gold quality
adrenal cortex	UBERON:0001235	97.11	gold quality
layer of synovial tissue	UBERON:0007616	97.11	gold quality
decidua	UBERON:0002450	97.05	gold quality
right adrenal gland cortex	UBERON:0035827	96.99	gold quality
placenta	UBERON:0001987	96.91	gold quality
upper lobe of left lung	UBERON:0008952	96.57	gold quality
periodontal ligament	UBERON:0008266	96.40	gold quality
right lung	UBERON:0002167	96.32	gold quality
upper lobe of lung	UBERON:0008948	96.30	gold quality
vermiform appendix	UBERON:0001154	95.97	gold quality
adrenal gland	UBERON:0002369	95.72	gold quality
minor salivary gland	UBERON:0001830	95.68	gold quality
pericardium	UBERON:0002407	95.63	gold quality
saliva-secreting gland	UBERON:0001044	95.47	gold quality
descending thoracic aorta	UBERON:0002345	95.24	gold quality
omental fat pad	UBERON:0010414	95.23	gold quality
peritoneum	UBERON:0002358	95.22	gold quality

Single-cell (SCXA)

Detected in 36 experiment(s), a significant marker in 35.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	5316.00
E-MTAB-6701	yes	3913.61
E-HCAD-24	yes	3401.14
E-MTAB-10855	yes	2861.82
E-MTAB-8498	yes	2686.78
E-MTAB-8530	yes	2205.89
E-HCAD-36	yes	2183.57
E-MTAB-7407	yes	1630.19
E-MTAB-9801	yes	1499.69
E-GEOD-149689	yes	1486.79
E-HCAD-32	yes	1099.81
E-MTAB-10885	yes	966.10
E-CURD-112	yes	959.58
E-MTAB-7381	yes	794.10
E-ANND-5	yes	602.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPB, CEBPG, CREB1, CTNNB1, FOS, FOSB, HOXC4, IRF6, KLF4, MEF2A, MEF2D, NFKB, PPARG, SP1, SP2, SP3, SPI1, STAT1, VDR, WT1

miRNA regulators (miRDB)

8 targeting CD14, 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-3658	99.96	73.87	4379
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-296-3P	99.21	66.56	474

Literature-anchored findings (GeneRIF, showing 40)

• The roles of crc and dimmed genes on the expression of diverse hormones in D. melanogaster and reported. (PMID:16651547)
• Cryptocephal, the Drosophila melanogaster ATF4, is a specific coactivator for ecdysone receptor isoform B2. (PMID:22912598)
• GCN2 and ATF4 are important regulators of 4E-BP transcription during normal drosophila development and aging. (PMID:27979906)
• ATF4 regulates the expression of one-carbon metabolism genes SHMT2 and NMDMC as a protective response to mitochondrial toxicity. (PMID:28211874)
• ATF4 activation reprograms nuclear gene expression and contributes to neuronal dysfunction (PMID:31645461)
• Roles of C/EBP class bZip proteins in the growth and cell competition of Rp (‘Minute’) mutants in Drosophila. (PMID:31909714)
• ATF4-Induced Warburg Metabolism Drives Over-Proliferation in Drosophila. (PMID:32433968)
• Translational induction of ATF4 during integrated stress response requires noncanonical initiation factors eIF2D and DENR. (PMID:32938929)
• CD14-dependent activation of NF-kappaB by filarial parasitic sheath proteins (PMID:11779220)
• Data suggest that soluble lipopolysaccharide receptor CD14 (sCD14) elevation is associated with the development of multiple organ dysfunction syndrome (MODS) after major burns. (PMID:11825494)
• results suggest that the enhanced CD14 expression in psoriasis is not attributable to functional variants of CD14 (-159C/T) (PMID:11841490)
• IFN-gamma primed CD14(high) human gingival fibroblasts to enhance production of IL-8 in response to LPS through augmentation of the CD14-TLR system (PMID:11854210)
• The important host receptor CD14 is partially implicated in TNF, IL-1, IL-6 and MCP-1 production, while CD14-independent pathways seem to be responsible for IL-8 production after S. suis stimulation. (PMID:11876746)
• Though Cd14 is known to faciitate binding of several bacterial ligands to TLR, no role could be found for CD14 in C. pneumoniae binding. (PMID:11932927)
• No association between the CD14 C(-260)T and CD18 codon 441 gene polymorphisms and the incidence of stroke was found in a large, prospective, matched case-control sample from the Physicians’ Health Study. (PMID:11935032)
• CD14 polymorphism is associated with smoking dependence (PMID:12011764)
• Human proteinase 3 can inhibits LPS-mediated TNF-alpha production through CD14 degradation (PMID:12067299)
• plasma factor LBP and cell surface receptor CD14 were necessary for LPS activation of p38, which was tightly associated with LPS priming of the PMN respiratory burst (PMID:12117913)
• TT genotype of CD14 associated with risk of atherosclerotic or microangiopathic stroke (PMID:12140663)
• CD14 has a role in mediating signaling responses to Aspergillus fumigatus (PMID:12171914)
• Data show that the TLR4-mediated LPS response in bladder epithelial cells also uses the co-receptor CD14 for efficient LPS signalling. (PMID:12174084)
• Porphyromonas gingivalis fimbriae activate human peripheral blood monocytes utilizing TLR2, CD14 and CD11a/CD18 as cellular receptors. (PMID:12207338)
• Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex (PMID:12324469)
• some heat-stable component of P. gingivalis, including LPS, may be responsible for the induction of IL-8 and MCP-1 in HUVECs by a CD14-dependent mechanism (PMID:12410798)
• lipopolysaccharide may induce proliferation of periodontal epithelial cells by upregulating keratinocyte growth factor 1 expression via the CD14 and Toll-like receptor signaling pathway (PMID:12438323)
• innate immune recognition of LTA via LBP, CD14, and TLR-2 represents an important mechanism in the pathogenesis of systemic complications in the course of infectious diseases brought about by Gram-positive pathogens. while TLR-4 and MD-2 are not involved. (PMID:12594207)
• The CD14 -159C/T polymorphism is associated with increased common carotid artery intima-media thickness in smokers (PMID:12624278)
• Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2 (PMID:12663765)
• first study to suggest an effect of a genetic polymorphism of the CD14 gene on both insulin sensitivity (healthy subjects and type 2 diabetic patients) and endothelial dysfunction (sICAM-1 levels) in type 2 diabetes mellitus (PMID:12679473)
• CD14 is not critical for phosphatidylserine-induced apoptosis in human macrophages (PMID:12700637)
• a new functional role of CD55 as a member of a multimeric LPS receptor complex. (PMID:12731067)
• data support the hypothesis that lipopolysaccharide binding protein can inhibit cell responses to lipopolysaccharide(LPS) by inhibiting LPS transfer from membrane CD14 to the Toll-like receptor 4-MD-2 signaling receptor (PMID:12754215)
• data suggest that peripheral blood cells are of negligible importance in LPS-induced production of inflammatory mediators in vivo and that LPS may activate genes via a CD14-independent pathway that is slower and less efficient (PMID:12757265)
• A significant association between the CD14 TT genotype and C. pneumoniae infection was found. (PMID:12825176)
• there may be a resistive exercise training-induced reduction in TLR4/CD14 expression in older women (PMID:12832426)
• results provided experimental evidence for existence of close association between CD14 and HIV coreceptor CXCR4 on human monocytic cells (PMID:12853157)
• The TT genotype of -159 C–>T CD14 is associated with nonatopic asthma and food allergy, particularly in white subjects. Thus CD14 is a candidate gene specifically for nonatopic asthma and not for asthma in general (PMID:12897754)
• The polymorphic maeker C-159T of CD14 was associated with serum total IgE concentration in atopic Chinese children. (PMID:12911501)
• increased serum levels in chronic Hepatitis B and C patients and inversely correlated with HBsAg in chronic Hepatitis B (PMID:12938192)
• Results show that the surface receptors TLR2/4 and CD14 are essential for in vitro cellular activation induced by Neisseria meningitidis lipopolysaccharide-containing outer membrane vesicles and purified lipopolysaccharides. (PMID:12942028)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd14	ENSMUSG00000051439
rattus_norvegicus	Cd14	ENSRNOG00000017819

Protein

Protein identifiers

Monocyte differentiation antigen CD14 — P08571 (reviewed: P08571)

Alternative names: My23 antigen, Myeloid cell-specific leucine-rich glycoprotein

All UniProt accessions (4): P08571, D6RD81, D6RFL4, E7EVL5

UniProt curated annotations — full annotation on UniProt →

Function. Coreceptor for bacterial lipopolysaccharide. In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MyD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Acts as a coreceptor for TLR2:TLR6 heterodimer in response to diacylated lipopeptides and for TLR2:TLR1 heterodimer in response to triacylated lipopeptides, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway. Binds electronegative LDL (LDL(-)) and mediates the cytokine release induced by LDL(-).

Subunit / interactions. Interacts with LPS-bound LPB. Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4. Interacts with LPAR1. Interacts with the TLR2:TLR6 or TLR2:TLR1 heterodimers; upon interaction with ligands such as diacylated lipopeptides and triacylated lipopeptides, respectively. Interacts with MYO18A. Interacts with FSTL1.

Subcellular location. Cell membrane. Secreted. Membrane raft. Golgi apparatus.

Tissue specificity. Detected on macrophages (at protein level). Expressed strongly on the surface of monocytes and weakly on the surface of granulocytes; also expressed by most tissue macrophages.

Post-translational modifications. N- and O- glycosylated. O-glycosylated with a core 1 or possibly core 8 glycan.

Domain organisation. The C-terminal leucine-rich repeat (LRR) region is required for responses to smooth LPS.

Induction. The expression in monocytes is highly induced by 27-hydroxycholesterol, priming monocytes/macrophages such that LPS-mediated inflammatory reaction is accelerated. Secretion of soluble CD14 is also enhanced.

RefSeq proteins (4): NP_000582, NP_001035110, NP_001167575, NP_001167576 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR016337	Monocyte_diff_Ag_CD14	Family
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF13516

UniProt features (30 total): repeat 11, glycosylation site 5, disulfide bond 4, chain 2, sequence variant 2, sequence conflict 2, signal peptide 1, region of interest 1, lipid moiety-binding region 1, propeptide 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4GLP	X-RAY DIFFRACTION	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08571-F1	85.36	0.72

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): 345

Disulfide bonds (4): 25–36, 34–51, 187–217, 241–272

Glycosylation sites (5): 37, 151, 282, 323, 336

Function

Pathways and Gene Ontology

Reactome pathways

42 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-140534	Caspase activation via Death Receptors in the presence of ligand
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166020	Transfer of LPS from LBP carrier to CD14
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-166166	MyD88-independent TLR4 cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-2562578	TRIF-mediated programmed cell death
R-HSA-5602498	MyD88 deficiency (TLR2/4)
R-HSA-5603041	IRAK4 deficiency (TLR2/4)
R-HSA-5686938	Regulation of TLR by endogenous ligand
R-HSA-6798695	Neutrophil degranulation
R-HSA-936964	Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)
R-HSA-937041	IKK complex recruitment mediated by RIP1
R-HSA-937072	TRAF6-mediated induction of TAK1 complex within TLR4 complex
R-HSA-975163	IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
R-HSA-9820960	Respiratory syncytial virus (RSV) attachment and entry
R-HSA-9824878	Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7
R-HSA-9833110	RSV-host interactions
R-HSA-9918485	Dengue Virus Attachment and Entry
R-HSA-109581	Apoptosis
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-1643685	Disease
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades

MSigDB gene sets: 470 (showing top): REACTOME_TRAF6_MEDIATED_INDUCTION_OF_TAK1_COMPLEX_WITHIN_TLR4_COMPLEX, GSE45365_NK_CELL_VS_CD11B_DC_DN, REACTOME_IKK_COMPLEX_RECRUITMENT_MEDIATED_BY_RIP1, MODULE_328, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, MCLACHLAN_DENTAL_CARIES_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_CELLULAR_RESPONSE_TO_LIPID, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOCC_SECRETORY_GRANULE, KEGG_MAPK_SIGNALING_PATHWAY

GO Biological Process (25): positive regulation of cytokine production (GO:0001819), cell surface pattern recognition receptor signaling pathway (GO:0002752), receptor-mediated endocytosis (GO:0006898), phagocytosis (GO:0006909), apoptotic process (GO:0006915), inflammatory response (GO:0006954), cell surface receptor signaling pathway (GO:0007166), positive regulation of lipopolysaccharide-mediated signaling pathway (GO:0031666), positive regulation of type I interferon production (GO:0032481), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-8 production (GO:0032757), positive regulation of tumor necrosis factor production (GO:0032760), toll-like receptor 4 signaling pathway (GO:0034142), positive regulation of toll-like receptor 4 signaling pathway (GO:0034145), innate immune response (GO:0045087), positive regulation of endocytosis (GO:0045807), cellular response to molecule of bacterial origin (GO:0071219), cellular response to lipopolysaccharide (GO:0071222), cellular response to lipoteichoic acid (GO:0071223), cellular response to diacyl bacterial lipopeptide (GO:0071726), cellular response to triacyl bacterial lipopeptide (GO:0071727), response to molecule of bacterial origin (GO:0002237), immune system process (GO:0002376), response to bacterium (GO:0009617), lipopolysaccharide-mediated signaling pathway (GO:0031663)

GO Molecular Function (7): lipopolysaccharide binding (GO:0001530), opsonin receptor activity (GO:0001847), lipopolysaccharide immune receptor activity (GO:0001875), peptidoglycan immune receptor activity (GO:0016019), lipoteichoic acid binding (GO:0070891), molecular carrier activity (GO:0140104), protein binding (GO:0005515)

GO Cellular Component (13): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), endosome membrane (GO:0010008), secretory granule membrane (GO:0030667), membrane raft (GO:0045121), lipopolysaccharide receptor complex (GO:0046696), extracellular exosome (GO:0070062), cell surface (GO:0009986), membrane (GO:0016020), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
TRIF (TICAM1)-mediated TLR4 signaling	4
Toll Like Receptor 4 (TLR4) Cascade	3
Toll-like Receptor Cascades	2
Toll Like Receptor 2 (TLR2) Cascade	2
Diseases associated with the TLR signaling cascade	2
Respiratory Syncytial Virus Infection Pathway	2
Antigen processing-Cross presentation	1
Caspase activation via extrinsic apoptotic signalling pathway	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Innate Immune System	1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
endocytosis	3
positive regulation of cytokine production	3
lipopolysaccharide-mediated signaling pathway	2
cellular response to molecule of bacterial origin	2
cellular response to oxygen-containing compound	2
carbohydrate derivative binding	2
pattern recognition receptor activity	2
binding	2
membrane	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
innate immune response activating cell surface receptor signaling pathway	1
pattern recognition receptor signaling pathway	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
defense response	1
signal transduction	1
positive regulation of response to biotic stimulus	1
positive regulation of signal transduction	1
regulation of lipopolysaccharide-mediated signaling pathway	1
positive regulation of response to external stimulus	1
regulation of type I interferon production	1
type I interferon production	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
cell surface toll-like receptor signaling pathway	1
toll-like receptor 4 signaling pathway	1
regulation of toll-like receptor 4 signaling pathway	1
positive regulation of pattern recognition receptor signaling pathway	1

Protein interactions and networks

STRING

1427 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD14	LBP	P18428	945
CD14	TLR4	O00206	939
CD14	LY96	Q9Y6Y9	743
CD14	TLR2	O60603	706
CD14	SP3	Q02447	514
CD14	PLCG2	P16885	497
CD14	DOCK1	Q14185	494
CD14	CSF2	P04141	493
CD14	TLR9	Q9NR96	475
CD14	TLR3	O15455	472
CD14	TLR7	Q9NYK1	464
CD14	TTR	P02766	459
CD14	CD55	P08174	454
CD14	MMP9	P14780	444
CD14	TXNL1	O43396	439

IntAct

29 interactions, top by confidence:

A	B	Type	Score
FSTL1	CD14	psi-mi:“MI:0915”(physical association)	0.660
CD14	FSTL1	psi-mi:“MI:0915”(physical association)	0.660
CD14	FSTL1	psi-mi:“MI:0407”(direct interaction)	0.660
	CD14	psi-mi:“MI:0407”(direct interaction)	0.440
TLR2	CD14	psi-mi:“MI:0407”(direct interaction)	0.440
IRAK3	CD14	psi-mi:“MI:0915”(physical association)	0.440
IRAK3	CD14	psi-mi:“MI:0403”(colocalization)	0.440
DERP2	CD14	psi-mi:“MI:0915”(physical association)	0.400
DIP2A	CD14	psi-mi:“MI:0915”(physical association)	0.400
NLRP12	CD14	psi-mi:“MI:0915”(physical association)	0.370
CD14	E7	psi-mi:“MI:0915”(physical association)	0.370
GJB2	CD14	psi-mi:“MI:0915”(physical association)	0.370
POLR2J	CD14	psi-mi:“MI:0915”(physical association)	0.370
CD14	PPP3R2	psi-mi:“MI:0915”(physical association)	0.370
TNFRSF1B	CD14	psi-mi:“MI:0915”(physical association)	0.370
ARFGAP3	CD14	psi-mi:“MI:0915”(physical association)	0.370
CD14	PHF20L1	psi-mi:“MI:0914”(association)	0.350
CD177	MYO1G	psi-mi:“MI:0914”(association)	0.350
CD14	MAN2B1	psi-mi:“MI:0914”(association)	0.350
RNF133	CD14	psi-mi:“MI:0914”(association)	0.350
FNDC5	A2ML1	psi-mi:“MI:0914”(association)	0.350
RNF133	NME2P1	psi-mi:“MI:0914”(association)	0.350
CD14	SERPINE1	psi-mi:“MI:0914”(association)	0.350
CD33	CD14	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (50): ANXA7 (Affinity Capture-MS), BUB1B (Affinity Capture-MS), AP3S1 (Affinity Capture-MS), PPP1R12B (Affinity Capture-MS), SVIL (Affinity Capture-MS), TAF1 (Affinity Capture-MS), TAF9 (Affinity Capture-MS), ICAM5 (Affinity Capture-MS), OASL (Affinity Capture-MS), EXO1 (Affinity Capture-MS), HPS5 (Affinity Capture-MS), PHF20L1 (Affinity Capture-MS), PHF21A (Affinity Capture-MS), BCAS3 (Affinity Capture-MS), C2orf44 (Affinity Capture-MS)

ESM2 similar proteins: A2ASA8, A5PJJ5, A6NE52, A6NHZ5, B6CZ46, E9QAM5, G7PWZ3, P08571, P10810, P33076, P52824, P79621, P86243, Q15048, Q15345, Q1L8H0, Q28680, Q32PG9, Q3U1Y4, Q3UJB3, Q3UWY1, Q3V1N1, Q3V3V9, Q3ZBI5, Q569B5, Q5BK65, Q5DU56, Q5M936, Q63035, Q63691, Q640Z9, Q66H52, Q68EF8, Q6F5E8, Q6GPH6, Q6P5E8, Q6QNU9, Q6R5P0, Q7RTR2, Q80VA5

Diamond homologs: P08571, P10810, Q28680, Q63691, Q6T752, Q95122, Q9QUN7, Q9R1F8, B2LT61, B2LT62, B2LT64, B2LT65, B5T267, Q0GC71, Q2PZH4, Q2V897, Q95LA9, Q9DD78, Q95M53, Q9DGB6, B3Y613, B3Y614, B3Y615, B3Y618, O00206, O60603, P0DUE1, P23515, P34595, P58727, Q0ZUL9, Q13478, Q15399, Q5I2M3, Q61098, Q689D1, Q6GV17, Q6R5N8, Q704V6, Q8BXA7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SPI1	“up-regulates quantity by expression”	CD14	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

225 predictions. Top by Δscore:

Variant	Effect	Δscore
5:140632325:T:C	acceptor_gain	1.0000
5:140633066:CACCA:C	donor_loss	0.9900
5:140633067:A:AC	donor_gain	0.9900
5:140633068:C:CA	donor_loss	0.9900
5:140633068:C:CC	donor_gain	0.9900
5:140632976:CGCTC:C	acceptor_gain	0.9800
5:140633061:ACACT:A	donor_loss	0.9800
5:140633062:CACTC:C	donor_loss	0.9800
5:140633063:ACTCA:A	donor_loss	0.9800
5:140632977:GCTCC:G	acceptor_loss	0.9700
5:140632978:CTC:C	acceptor_gain	0.9700
5:140632979:TCC:T	acceptor_loss	0.9700
5:140632980:CCT:C	acceptor_loss	0.9700
5:140632981:C:A	acceptor_loss	0.9700
5:140632982:T:G	acceptor_loss	0.9700
5:140632979:TC:T	acceptor_gain	0.9600
5:140632980:CC:C	acceptor_gain	0.9600
5:140632981:C:CC	acceptor_gain	0.9600
5:140633067:AC:A	donor_gain	0.9600
5:140633068:CC:C	donor_gain	0.9600
5:140633068:CCA:C	donor_gain	0.9600
5:140633574:T:TA	donor_gain	0.9500
5:140632325:T:TC	acceptor_gain	0.9200
5:140632977:GCTC:G	acceptor_gain	0.9200
5:140632978:CTCC:C	acceptor_gain	0.9200
5:140632979:TCCT:T	acceptor_gain	0.9200
5:140633068:CCAT:C	donor_gain	0.9200
5:140633068:CCATG:C	donor_gain	0.9200
5:140633548:C:CT	donor_gain	0.9200
5:140633549:T:TT	donor_gain	0.9200

AlphaMissense

2374 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:140632162:C:A	W274C	0.979
5:140632162:C:G	W274C	0.979
5:140632832:C:G	C51S	0.979
5:140632833:A:T	C51S	0.979
5:140632849:C:A	W45C	0.979
5:140632849:C:G	W45C	0.979
5:140632871:A:C	F38C	0.979
5:140632833:A:G	C51R	0.976
5:140632877:C:G	C36S	0.970
5:140632878:A:T	C36S	0.970
5:140632064:T:A	N307I	0.965
5:140631997:A:C	N329K	0.964
5:140631997:A:T	N329K	0.964
5:140632079:A:T	L302H	0.964
5:140632831:A:C	C51W	0.963
5:140632870:G:C	F38L	0.963
5:140632870:G:T	F38L	0.963
5:140632872:A:G	F38L	0.963
5:140632063:G:C	N307K	0.962
5:140632063:G:T	N307K	0.962
5:140632207:G:C	N259K	0.962
5:140632207:G:T	N259K	0.962
5:140632622:A:G	L121P	0.962
5:140632877:C:T	C36Y	0.960
5:140632322:A:C	F221C	0.956
5:140632883:C:G	C34S	0.956
5:140632884:A:T	C34S	0.956
5:140632073:A:G	L304P	0.952
5:140632832:C:T	C51Y	0.952
5:140632910:C:G	C25S	0.951

dbSNP variants (sampled 300 via entrez): RS1002825640 (5:140631600 TGAG>T), RS1003752066 (5:140634734 C>G), RS1003922204 (5:140634314 G>A), RS1006243753 (5:140631697 T>C), RS1006335701 (5:140631323 G>A), RS1007538218 (5:140631528 C>A,T), RS1008156682 (5:140635496 A>G), RS1009953211 (5:140634766 C>T), RS1010546149 (5:140633140 C>G), RS1010660681 (5:140633526 C>T), RS1011045674 (5:140632732 G>A), RS1012601497 (5:140633145 G>A,C), RS1013603088 (5:140634742 G>A), RS1013693482 (5:140634377 A>G), RS1015211008 (5:140633947 C>A)

Disease associations

OMIM: gene MIM:158120 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006585_109	Blood protein levels	4.000000e-12
GCST006803_54	Schizophrenia	8.000000e-07
GCST010002_39	Refractive error	2.000000e-14
GCST010146_22	Serum immune biomarker levels	7.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004872	inflammatory biomarker measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2384897 (SINGLE PROTEIN), CHEMBL3038513 (PROTEIN COMPLEX)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2569190	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Ulcerative Colitis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2569190	CD14, TMCO6	3	2.25	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — CD molecules

ChEMBL bioactivities

4 potent at pChembl≥5 of 6 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.70	IC50	200	nM	CHEMBL4072822
6.16	IC50	700	nM	CHEMBL4081306
5.24	IC50	5700	nM	CHEMBL4105554
5.00	IC50	1e+04	nM	CHEMBL4093531

PubChem BioAssay actives

4 with measured affinity, of 27 total; 4 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
2-[4-[[5,11,17,23-tetratert-butyl-26,27,28-tris[4-(diaminomethylideneamino)butoxy]-25-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(24),3,5,7(28),9,11,13(27),15(26),16,18,21(25),22-dodecaenyl]oxy]butyl]guanidine;tetrahydrochloride	1447912: Binding affinity to CD14/MD2 (unknown origin) expressed in HEK-Blue cells co-expressing TLR4 assessed as inhibition of LPS-induced TLR4 signaling preincubated for 30 mins followed by LPS stimulation measured after overnight incubation by secreted embryonic alkaline phosphatase reporter gene assay	ic50	0.2000	uM
2-[11,17,23-tris(diaminomethylideneamino)-25,26,27-tripropoxy-5-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3(28),4,6,9(27),10,12,15,17,19(26),21,23-dodecaenyl]guanidine;tetrahydrochloride	1447912: Binding affinity to CD14/MD2 (unknown origin) expressed in HEK-Blue cells co-expressing TLR4 assessed as inhibition of LPS-induced TLR4 signaling preincubated for 30 mins followed by LPS stimulation measured after overnight incubation by secreted embryonic alkaline phosphatase reporter gene assay	ic50	0.7000	uM
2-[11,17,23-tris(diaminomethylideneamino)-25,26,27-trihexoxy-5-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3(28),4,6,9(27),10,12,15,17,19(26),21,23-dodecaenyl]guanidine;tetrahydrochloride	1447912: Binding affinity to CD14/MD2 (unknown origin) expressed in HEK-Blue cells co-expressing TLR4 assessed as inhibition of LPS-induced TLR4 signaling preincubated for 30 mins followed by LPS stimulation measured after overnight incubation by secreted embryonic alkaline phosphatase reporter gene assay	ic50	5.7000	uM
2-[3-[[5,11,17,23-tetratert-butyl-26,27,28-tris[3-(diaminomethylideneamino)propoxy]-25-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(24),3,5,7(28),9,11,13(27),15(26),16,18,21(25),22-dodecaenyl]oxy]propyl]guanidine;tetrahydrochloride	1447912: Binding affinity to CD14/MD2 (unknown origin) expressed in HEK-Blue cells co-expressing TLR4 assessed as inhibition of LPS-induced TLR4 signaling preincubated for 30 mins followed by LPS stimulation measured after overnight incubation by secreted embryonic alkaline phosphatase reporter gene assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Calcitriol	increases expression, increases reaction, affects cotreatment, affects binding, decreases reaction	18
Lipopolysaccharides	decreases reaction, increases expression, affects reaction, increases reaction, increases secretion (+4 more)	8
Tetradecanoylphorbol Acetate	increases expression, increases reaction	7
Tretinoin	increases expression, increases reaction, affects cotreatment	6
sodium arsenite	affects methylation, decreases expression, increases expression	5
Benzo(a)pyrene	affects cotreatment, increases expression, increases reaction, decreases expression, decreases methylation	5
perfluorooctane sulfonic acid	affects expression, decreases expression, increases expression	3
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases reaction, decreases reaction, increases expression	3
Resveratrol	affects cotreatment, increases expression	3
Decitabine	affects cotreatment, increases expression, increases reaction	3
Arsenic Trioxide	decreases reaction, increases expression, increases reaction, decreases expression	3
Troglitazone	decreases expression, increases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	3
Nickel	decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance, decreases methylation	3
paricalcitol	affects cotreatment, increases expression	2
SB 203580	decreases reaction, increases expression, increases reaction	2
pyrazolanthrone	decreases reaction, increases expression	2
lipopolysaccharide, Escherichia coli O111 B4	decreases reaction, increases expression, increases reaction, affects cotreatment, increases response to substance	2
lithocholic acid acetate	increases expression	2
Zoledronic Acid	increases expression	2
Arsenic	increases expression, decreases expression, increases abundance	2
Cadmium	decreases reaction, affects cotreatment, decreases expression, increases expression	2
Cholecalciferol	affects cotreatment, increases expression, decreases reaction	2
Lithocholic Acid	increases expression, increases reaction	2
Testosterone	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression	2
Cyclosporine	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
SHP099	increases expression, increases reaction	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2389992	Binding	Activation of human TLR4/MD-2/CD14 transfected in HEK293 cells at 10 uM after 20 to 24 hrs by SEAP assay	Identification of substituted pyrimido[5,4-b]indoles as selective Toll-like receptor 4 ligands. — J Med Chem

Cellosaurus cell lines

25 cell lines: 14 transformed cell line, 11 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8CR	HEK-Blue-Lucia hTLR2 (NF/IL8)	Transformed cell line	Female
CVCL_B8CT	Abcam HCT 116 CD14 KO	Cancer cell line	Male
CVCL_B8TJ	Abcam MCF-7 CD14 KO	Cancer cell line	Female
CVCL_B9F1	Abcam A-549 CD14 KO	Cancer cell line	Male
CVCL_D7AD	Leeporter HeLa TLR4/IL-8 luciferase	Cancer cell line	Female
CVCL_D7LZ	Ubigene A-549 CD14 KO	Cancer cell line	Male
CVCL_D9BE	Ubigene HEK293 CD14 KO	Transformed cell line	Female
CVCL_E1JV	HyCyte GES-1 KO-hCD14	Transformed cell line	Sex unspecified
CVCL_E2QR	THP-1 TLR4-CD14 NFkappaB-eGFP	Cancer cell line	Male
CVCL_E6V0	Genomeditech HEK-293 H_TLR4 Reporter	Transformed cell line	Female

Clinical trials (associated diseases)

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