CRP

Summary

CRP (C-reactive protein, HGNC:2367) is a protein-coding gene on chromosome 1q23.2, encoding C-reactive protein (P02741). Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphorylcholine.

The protein encoded by this gene belongs to the pentraxin family which also includes serum amyloid P component protein and pentraxin 3. Pentraxins are involved in complement activation and amplification via communication with complement initiation pattern recognition molecules, but also complement regulation via recruitment of complement regulators. The encoded protein has a calcium dependent ligand binding domain with a distinctive flattened beta-jellyroll structure. It exists in two forms as either a pentamer in circulation or as a nonsoluble monomer in tissues. It is involved in several host defense related functions based on its ability to recognize foreign pathogens and damaged cells of the host and to initiate their elimination by interacting with humoral and cellular effector systems in the blood. Consequently, the level of this protein in plasma increases greatly during acute phase response to tissue injury, infection, or other inflammatory stimuli. Elevated expression of the encoded protein is associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection.

Source: NCBI Gene 1401 — RefSeq curated summary.

At a glance

• GWAS associations: 47
• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_000567

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2367
Approved symbol	CRP
Name	C-reactive protein
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Aliases	PTX1
Ensembl gene	ENSG00000132693
Ensembl biotype	protein_coding
OMIM	123260
Entrez	1401

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000255030, ENST00000368110, ENST00000368111, ENST00000368112, ENST00000437342, ENST00000473196, ENST00000489317

RefSeq mRNA: 4 — MANE Select: NM_000567 NM_000567, NM_001329057, NM_001329058, NM_001382703

CCDS: CCDS30911, CCDS86024, CCDS91082

Canonical transcript exons

ENST00000255030 — 2 exons

Exon	Start	End
ENSE00001287766	159712289	159714138
ENSE00001328381	159714425	159714589

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 98.59.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 38.5626 / max 23207.0163, expressed in 14 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15414	38.3582	13
15410	0.0652	5
15411	0.0605	4
15413	0.0435	4
15412	0.0353	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.59	gold quality
liver	UBERON:0002107	96.07	gold quality
islet of Langerhans	UBERON:0000006	95.77	gold quality
gall bladder	UBERON:0002110	95.11	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.15	gold quality
pancreas	UBERON:0001264	84.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.85	silver quality
body of pancreas	UBERON:0001150	80.17	gold quality
epithelial cell of pancreas	CL:0000083	79.54	gold quality
type B pancreatic cell	CL:0000169	75.31	silver quality
lower esophagus mucosa	UBERON:0035834	70.29	gold quality
right coronary artery	UBERON:0001625	67.06	gold quality
ectocervix	UBERON:0012249	66.11	gold quality
colonic epithelium	UBERON:0000397	64.75	silver quality
pancreatic ductal cell	CL:0002079	64.18	silver quality
descending thoracic aorta	UBERON:0002345	63.36	gold quality
metanephros cortex	UBERON:0010533	63.11	gold quality
endocervix	UBERON:0000458	61.17	gold quality
right lung	UBERON:0002167	60.14	gold quality
mucosa of stomach	UBERON:0001199	59.95	gold quality
right ovary	UBERON:0002118	59.68	gold quality
endometrium epithelium	UBERON:0004811	58.45	gold quality
right uterine tube	UBERON:0001302	56.88	gold quality
uterine cervix	UBERON:0000002	56.82	gold quality
right adrenal gland	UBERON:0001233	56.76	gold quality
left uterine tube	UBERON:0001303	56.23	gold quality
body of uterus	UBERON:0009853	56.05	gold quality
coronary artery	UBERON:0001621	56.04	gold quality
left coronary artery	UBERON:0001626	56.04	gold quality
left adrenal gland	UBERON:0001234	55.30	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	15793.75
E-MTAB-10137	yes	7496.92
E-MTAB-5061	yes	7044.97
E-MTAB-8495	yes	1463.89
E-GEOD-83139	yes	11.87
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
CCL2	Activation
CXCL8	Activation
GCH1	Repression
LPL	Activation

Upstream regulators (CollecTRI, top): AP1, CEBPB, CEBPG, CREB3L3, DDIT3, DNMT1, ESRRG, FOS, HNF1A, NFKB1, NFKB, NR1H3, NR1H4, NR3C1, PITX2, POU2F1, PPARA, REL, RELA, STAT3, TBP, TOX

miRNA regulators (miRDB)

38 targeting CRP, 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-7110-3P	100.00	73.18	2486
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-609	99.82	64.26	505
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-5691	98.23	67.02	1335

Literature-anchored findings (GeneRIF, showing 40)

• C-reactive protein was higher in arrhythmia than in control patients. (PMID:11739301)
• Acute phase concentrations of CRP induce signaling through the intrinsic immunoreceptor tyrosine-based activation motif of the cytoplasmic domain of FcgammaRIIa, thus providing a molecular basis for the role of CRP in host protection. (PMID:11801683)
• Polymorphism in the CRP gene contributes to a variation in baseline levels of CRP. (PMID:11857055)
• CRP concentrations are a potent independent predictor of future vascular events. (PMID:11947917)
• role in resolution of bacterial infection - review (PMID:11964845)
• data indicate that IL-1 gene polymorphisms known to affect the inflammatory response are highly related to plasma levels of CRP and fibrinogen in patients referred for coronary angiography (PMID:11991668)
• Macrophage uptake of low-density lipoprotein bound to aggregated C-reactive protein: possible mechanism of foam-cell formation in atherosclerotic lesions (PMID:12033985)
• In a mouse model of systemic infection with highly virulent Streptococcus pneumoniae, protection from lethality by human C-reactive protein and endogenous anti-phosphocholine antibodies requires complement, but not Fc gamma receptors. (PMID:12055255)
• CRP can bind to modified lipoproteins, notably to the non-esterified cholesterol on their surface. These interactions may be related to the suggested role of CRP in the local inflammation present in atherosclerotic plaques. (PMID:12102655)
• establishment of age-dependent normal reference range (PMID:12104096)
• REVIEW: CRP (inflammatory markers) and coronary heart disease (PMID:12151853)
• C-Reactive Protein Attenuates Nitric Oxide Production and Inhibits Angiogenesis (PMID:12186793)
• loss of pentameric symmetry is associated with delayed apoptosis of human neutrophils (PMID:12198121)
• has been shown to reflect systemic and, perhaps, vascular inflammation and to predict future cardiovascular events in asymptomatic individuals (review) (PMID:12213988)
• Phe66 is the major determinant of CRP-phosphocholine (PCh) interaction and is critical for binding of CRP to PCh residues in pneumococcal C-polysaccharide. (PMID:12218140)
• C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells (PMID:12234944)
• C-reactive protein has a role in the immune response to oxidized phosphorylcholine-bearing phospholipids in oxidized LDL and on the cell membrane of apoptotic cells. (PMID:12244213)
• an investigation as to whether the levels of this protein in IDDM are related to coronary calcification (PMID:12351483)
• C-reactive protein directly stimulates monocyte adhesion to vascular endothelial cells. (PMID:12390313)
• IL-1 induces CRP expression through 2 overlapping response elements, the binding sites for CCAAT-box/enhancer-binding protein-beta (C/EBP-beta) and p50-nuclear factor-kappaB (p50-NFkappaB). (PMID:12393563)
• CRP exerts an endothelium-independent vasorelaxing effect via potassium channels in vitro, suggesting a role for CRP in the regulation of vascular tone. (PMID:12426217)
• Cardiorespiratory fitness levels in men are inversely associated with CRP values and the prevalence of elevated CRP values. (PMID:12426218)
• Elevated CRP concentrations associated with hemodialysis may be useful for the prediction of proatherogenic reactivity and cardiac hypertrophy. (PMID:12460042)
• The protective effect of human CRP administered to mice exposed to an inflammatory stimulus appears to be mediated by CRP binding to FcgammaRI and FcgammaRII, thus enhancing secretion of the anti-inflammatory cytokine IL-10 and down-regulation of IL-12. (PMID:12471137)
• Obesity is associated with higher fasting insulin level, and fasting insulin is associated with C-reactive protein level, in healthy 2- to 3-year-old children (PMID:12529491)
• association between higher physical activity and lower serum CRP levels is dependent on the lower body fat of more active women, yet independent of oral hormone replacement therapy (PMID:12552583)
• Physical fitness is inversely related to CRP level in children, a relationship that is more pronounced in boys than in girls. (PMID:12563060)
• The kidney as a second site of human C-reactive protein formation in vivo (PMID:12594844)
• As summarized in this review, CRP mediates host defense and protection because it supports three major effector functions: activation of complement, opsonization, and the induction of phagocytosis. (PMID:12616974)
• C-reactive protein expression was found to be an independent prognosticator in patients with esophageal squamous cell carcinoma in the multivariate analysis (PMID:12637157)
• Leishmania donovani can use CRP to improve infection without inducing detrimental macrophage activation (PMID:12654086)
• data suggest a transcriptional mechanism leading to decreased adiponectin plasma levels in obese women and demonstrate that low levels of adiponectin are associated with higher levels of C-reactive protein and interleukin-6 (PMID:12663465)
• in subjects with hypoalphalipoproteinemia or hyperalphalipoproteinemia, HDL-cholesterol levels may account for plasma C-reactive protein variations independent of other potential cardiovascular risk (PMID:12701054)
• the relation between CRP and HbA(1c) in a large national sample of individuals with diabetes (PMID:12716818)
• Data suggest that C-reactive protein seems to enhance local inflammatory reactions ensuing in human myocardial infarcts of more than 12 hours duration. (PMID:12819031)
• Elevated CRP is a risk factor for ischemic stroke, independent of atherosclerosis severity as measured by carotid intimal-medial thickness (PMID:12821545)
• CRP levels significantly correlate with calculated 10-year Framingham Coronary Heart Disease Risk in men and women not taking hormone replacement therapy but minimally with most individual components of the FCR (PMID:12835213)
• In acute myocardial infarction elevated CRP levels may reflect the inflammatory activity of a ruptured plaque (PMID:12835218)
• The CRP gene +1444C>T variant influences basal and stimulated CRP level. These findings have implications both for the prediction and pathogenesis of coronary heart disease. (PMID:12842840)
• CRP was reduced in one case treated with infliximab. (PMID:12850811)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	apcs	ENSDARG00000045089
mus_musculus	Crp	ENSMUSG00000037942

Paralogs (5): NPTX2 (ENSG00000106236), APCS (ENSG00000132703), PTX3 (ENSG00000163661), NPTX1 (ENSG00000171246), PTX4 (ENSG00000251692)

Protein

Protein identifiers

C-reactive protein — P02741 (reviewed: P02741)

All UniProt accessions (3): P02741, C9JRE9, Q5VVP7

UniProt curated annotations — full annotation on UniProt →

Function. Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphorylcholine. Can interact with DNA and histones and may scavenge nuclear material released from damaged circulating cells.

Subunit / interactions. Homopentamer. Pentraxin (or pentaxin) have a discoid arrangement of 5 non-covalently bound subunits. Interacts with FCN1; may regulate monocyte activation by FCN1.

Subcellular location. Secreted.

Tissue specificity. Found in plasma.

Cofactor. Binds 2 calcium ions per subunit.

Induction. The concentration of CRP in plasma increases greatly during acute phase response to tissue injury, infection or other inflammatory stimuli. It is induced by IL1/interleukin-1 and IL6/interleukin-6.

Miscellaneous. This protein owes its name to its ability precipitate pneumococcal C-polysaccharide in the presence of calcium.

Similarity. Belongs to the pentraxin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P02741-1	1	yes
P02741-2	2

RefSeq proteins (4): NP_000558, NP_001315986, NP_001315987, NP_001369632 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001759	PTX_dom	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR030476	Pentaxin_CS	Conserved_site
IPR051005	Pentraxin_domain	Family

Pfam: PF00354

UniProt features (43 total): strand 17, binding site 8, sequence conflict 5, helix 4, chain 2, turn 2, signal peptide 1, modified residue 1, disulfide bond 1, splice variant 1, domain 1

Structure

Experimental structures (PDB)

24 structures.

PDB	Method	Resolution (Å)
3PVN	X-RAY DIFFRACTION	1.98
9VCA	ELECTRON MICROSCOPY	2.4
1B09	X-RAY DIFFRACTION	2.5
3L2Y	X-RAY DIFFRACTION	2.7
9U4E	ELECTRON MICROSCOPY	2.78
7PK9	ELECTRON MICROSCOPY	2.8
7PKF	ELECTRON MICROSCOPY	2.8
1GNH	X-RAY DIFFRACTION	3
3PVO	X-RAY DIFFRACTION	3
7PKH	ELECTRON MICROSCOPY	3
1LJ7	X-RAY DIFFRACTION	3.15
7PKB	ELECTRON MICROSCOPY	3.2
7PKD	ELECTRON MICROSCOPY	3.3
7PKE	ELECTRON MICROSCOPY	3.3
7PKG	ELECTRON MICROSCOPY	3.3
8WV4	ELECTRON MICROSCOPY	3.3
7TBA	X-RAY DIFFRACTION	3.5
8WV5	ELECTRON MICROSCOPY	3.5
9JO9	ELECTRON MICROSCOPY	3.65
9JO7	ELECTRON MICROSCOPY	3.68
9JNY	ELECTRON MICROSCOPY	3.74
9K94	ELECTRON MICROSCOPY	4.04
9KMP	ELECTRON MICROSCOPY	4.1
9KMS	ELECTRON MICROSCOPY	4.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02741-F1	94.24	0.91

Antibody-complex structures (SAbDab): 6 — 9JO7, 9JO9, 9K94, 9KMP, 9KMS, 9VCA

Functional residue map

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

Ligand- & substrate-binding residues (8): 158; 168; 78; 79; 156; 156; 157; 158

Post-translational modifications (1): 19

Disulfide bonds (1): 54–115

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-173623	Classical antibody-mediated complement activation

MSigDB gene sets: 153 (showing top): GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_LIPID_STORAGE, MULLIGHAN_NPM1_SIGNATURE_3_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, REACTOME_CREATION_OF_C4_AND_C2_ACTIVATORS, GOBP_REGULATION_OF_SUPEROXIDE_ANION_GENERATION, GOBP_SUPEROXIDE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_LEUKOCYTE_PROLIFERATION, GOBP_CYTOKINE_PRODUCTION

GO Biological Process (12): acute-phase response (GO:0006953), inflammatory response (GO:0006954), opsonization (GO:0008228), positive regulation of gene expression (GO:0010628), negative regulation of macrophage derived foam cell differentiation (GO:0010745), negative regulation of lipid storage (GO:0010888), regulation of interleukin-8 production (GO:0032677), positive regulation of superoxide anion generation (GO:0032930), negative regulation of mononuclear cell proliferation (GO:0032945), vasoconstriction (GO:0042310), innate immune response (GO:0045087), defense response to Gram-positive bacterium (GO:0050830)

GO Molecular Function (8): complement component C1q complex binding (GO:0001849), calcium ion binding (GO:0005509), low-density lipoprotein particle binding (GO:0030169), choline binding (GO:0033265), identical protein binding (GO:0042802), low-density lipoprotein particle receptor binding (GO:0050750), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Creation of C4 and C2 activators	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cation binding	2
acute inflammatory response	1
defense response	1
immune effector process	1
phagocytosis, recognition	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
negative regulation of cell differentiation	1
regulation of lipid storage	1
lipid storage	1
negative regulation of cellular process	1
negative regulation of lipid localization	1
regulation of cytokine production	1
interleukin-8 production	1
regulation of superoxide anion generation	1
superoxide anion generation	1
positive regulation of reactive oxygen species metabolic process	1
mononuclear cell proliferation	1
regulation of mononuclear cell proliferation	1
negative regulation of leukocyte proliferation	1
blood vessel diameter maintenance	1
immune response	1
defense response to symbiont	1
defense response to bacterium	1
opsonin binding	1
complement binding	1
protein-containing complex binding	1
metal ion binding	1
lipoprotein particle binding	1
protein binding	1
lipoprotein particle receptor binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3430 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRP	FCGR2A	P12318	990
CRP	C3	P01024	973
CRP	CFH	P08603	970
CRP	IL6	P05231	969
CRP	OLR1	P78380	965
CRP	CFHR4	Q92496	953
CRP	TNF	P01375	938
CRP	ALB	P02768	918
CRP	GPT	P24298	917
CRP	LEP	P41159	914
CRP	HP	P00737	894
CRP	F2	P00734	887
CRP	INS	P01308	887
CRP	IL1B	P01584	883
CRP	ADIPOQ	Q15848	882

IntAct

149 interactions, top by confidence:

A	B	Type	Score
CFH	CRP	psi-mi:“MI:0407”(direct interaction)	0.980
CRP	CFH	psi-mi:“MI:0915”(physical association)	0.980
CRP	CFH	psi-mi:“MI:0407”(direct interaction)	0.980
CFH	CRP	psi-mi:“MI:0915”(physical association)	0.980

BioGRID (97): GMPPA (Two-hybrid), CRP (Two-hybrid), CHST3 (Affinity Capture-MS), LAMA5 (Affinity Capture-MS), PRSS23 (Affinity Capture-MS), TMEM2 (Affinity Capture-MS), AGRN (Affinity Capture-MS), SPTB (Affinity Capture-MS), GDF11 (Affinity Capture-MS), C1GALT1 (Affinity Capture-MS), UBR3 (Affinity Capture-MS), QSOX1 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), TIMP3 (Affinity Capture-MS), LAMA1 (Affinity Capture-MS)

ESM2 similar proteins: A1XQX0, A1XQX2, A1XQX8, A8MV57, D0PRN3, O19062, O19063, P02741, P02742, P02743, P06205, P06206, P06207, P07629, P12246, P14847, P15697, P23680, P47971, P48199, P49254, P49255, P49262, P49263, Q07203, Q07310, Q0IIP8, Q0V8S9, Q0V8T0, Q0V8T3, Q0V8T4, Q0V8T5, Q0V8T6, Q0V8T7, Q0V8T8, Q0V8T9, Q15818, Q3T004, Q3T166, Q62443

Diamond homologs: A0A1D5NSM8, A0JNA2, A2AVA0, A2AX52, D3YXF5, O02839, O19063, O35764, O43405, O70340, O76536, O89029, O95502, O96530, P02741, P02743, P06205, P06206, P06207, P06681, P07202, P07629, P08607, P09871, P0C6B8, P10643, P12246, P13944, P14151, P14847, P15697, P18337, P23680, P32018, P47970, P47971, P47972, P48199, P49254, P49262

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
CRP	“down-regulates quantity by repression”	IL10	“translation regulation”
CRP	“down-regulates quantity”	IL10	“post transcriptional regulation”
CRP	“up-regulates quantity by expression”	LPL	“transcriptional regulation”
CRP	“up-regulates quantity by expression”	CXCL8	“transcriptional regulation”
CRP	“up-regulates quantity by expression”	CCL2	“transcriptional regulation”
CFH	“down-regulates activity”	CRP	binding
CRP	“down-regulates activity”	GCH1
CRP	“down-regulates quantity by repression”	GCH1	“transcriptional regulation”
CRP	“down-regulates quantity by destabilization”	NOS3

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of Complement cascade	7	74.2×	7e-10
Neutrophil degranulation	5	5.2×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
complement activation	6	149.8×	4e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

210 predictions. Top by Δscore:

Variant	Effect	Δscore
1:159714147:C:CT	acceptor_gain	0.9900
1:159714148:A:T	acceptor_gain	0.9900
1:159714420:CTTA:C	donor_loss	0.9900
1:159714422:TA:T	donor_loss	0.9900
1:159714423:A:AG	donor_loss	0.9900
1:159714424:CCTGT:C	donor_gain	0.9900
1:159714134:CATGT:C	acceptor_gain	0.9800
1:159714136:TGT:T	acceptor_gain	0.9700
1:159714139:C:CC	acceptor_gain	0.9700
1:159714147:C:T	acceptor_gain	0.9700
1:159714138:TCT:T	acceptor_loss	0.9600
1:159714139:CT:C	acceptor_loss	0.9600
1:159714423:A:AC	donor_gain	0.9600
1:159714424:C:CC	donor_gain	0.9600
1:159714137:GT:G	acceptor_gain	0.9300
1:159714135:ATGT:A	acceptor_gain	0.9000
1:159714422:TAC:T	donor_gain	0.8800
1:159714421:TTACC:T	donor_gain	0.8700
1:159714493:T:TA	donor_gain	0.8700
1:159714423:ACCTG:A	donor_gain	0.8400
1:159712795:C:CC	acceptor_gain	0.8300
1:159714419:CCTTA:C	donor_gain	0.8300
1:159714420:CTTAC:C	donor_gain	0.8300
1:159714424:C:G	donor_gain	0.8200
1:159714418:CCCTT:C	donor_gain	0.8000
1:159713614:C:CT	acceptor_gain	0.7900
1:159714141:G:C	acceptor_gain	0.7500
1:159714141:G:GC	acceptor_gain	0.7200
1:159713614:C:T	acceptor_gain	0.7000
1:159714005:A:AC	donor_gain	0.6400

AlphaMissense

1466 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:159713846:C:A	W118C	0.983
1:159713846:C:G	W118C	0.983
1:159714113:A:C	F29L	0.974
1:159714113:A:T	F29L	0.974
1:159714115:A:G	F29L	0.974
1:159714114:A:C	F29C	0.970
1:159713660:C:A	W180C	0.966
1:159713660:C:G	W180C	0.966
1:159713729:C:A	Q157H	0.965
1:159713729:C:G	Q157H	0.965
1:159713585:C:A	W205C	0.964
1:159713585:C:G	W205C	0.964
1:159713848:A:G	W118R	0.960
1:159713848:A:T	W118R	0.960
1:159713662:A:G	W180R	0.959
1:159713662:A:T	W180R	0.959
1:159713587:A:G	W205R	0.952
1:159713587:A:T	W205R	0.952
1:159713983:C:G	A73P	0.952
1:159714045:G:A	T52I	0.944
1:159714114:A:G	F29S	0.943
1:159713990:G:C	F70L	0.941
1:159713990:G:T	F70L	0.941
1:159713992:A:G	F70L	0.941
1:159713958:A:G	I81T	0.940
1:159714087:A:T	V38E	0.939
1:159714040:A:G	C54R	0.937
1:159713739:C:T	G154E	0.936
1:159713991:A:G	F70S	0.936
1:159713792:C:A	R136S	0.935

dbSNP variants (sampled 300 via entrez): RS1000114735 (1:159714247 C>T), RS1000146741 (1:159712416 C>G), RS1000501536 (1:159712712 A>C), RS1000518476 (1:159712652 G>A), RS1000957947 (1:159712626 T>C), RS1001167099 (1:159715530 C>T), RS1001611715 (1:159715191 T>A), RS1001948453 (1:159716518 A>C), RS1002614565 (1:159713960 C>A,T), RS1004065905 (1:159713455 C>A,T), RS1004522426 (1:159713287 G>C), RS1005775841 (1:159715748 C>T), RS1006776031 (1:159714603 C>G,T), RS1007872919 (1:159716394 T>A,C), RS1007913028 (1:159713023 C>A)

Disease associations

OMIM: gene MIM:123260 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

47 associations (top):

Study	Trait	p-value
GCST000083_15	Select biomarker traits	3.000000e-08
GCST000172_3	Lung cancer	7.000000e-06
GCST000178_7	C-reactive protein	6.000000e-28
GCST000179_1	C-reactive protein	7.000000e-06
GCST000189_27	Protein quantitative trait loci	6.000000e-06
GCST000292_6	Metabolic traits	3.000000e-22
GCST000430_3	C-reactive protein	8.000000e-44
GCST000933_1	C-reactive protein	4.000000e-21
GCST000965_19	C-reactive protein levels	2.000000e-186
GCST001093_1	C-reactive protein	1.000000e-09
GCST001385_4	Inflammatory biomarkers	2.000000e-20
GCST001472_1	C-reactive protein	2.000000e-13
GCST001650_1	C-reactive protein	1.000000e-37
GCST001650_11	C-reactive protein	3.000000e-10
GCST001650_5	C-reactive protein	1.000000e-09
GCST001650_8	C-reactive protein	4.000000e-73
GCST002086_2	C-reactive protein	4.000000e-21
GCST002424_1	C-reactive protein levels	2.000000e-16
GCST002640_1	Inflammatory biomarkers in Kawasaki disease	1.000000e-13
GCST003211_1	C-reactive protein levels in ischemic stroke	1.000000e-09
GCST003681_8	C-reactive protein levels or triglyceride levels (pleiotropy)	4.000000e-120
GCST004530_1	C-reactive protein levels	7.000000e-12
GCST006012_3	C-reactive protein levels	1.000000e-64
GCST006585_243	Blood protein levels	2.000000e-14
GCST007614_29	C-reactive protein levels	1.000000e-180
GCST007614_33	C-reactive protein levels	1.000000e-86
GCST007614_42	C-reactive protein levels	0.000000e+00
GCST007615_10	C-reactive protein levels	0.000000e+00
GCST007615_57	C-reactive protein levels	2.000000e-13
GCST007615_58	C-reactive protein levels	4.000000e-66

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0004530	triglyceride measurement
EFO:0004747	protein measurement
EFO:0008391	erythropoetin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1130864	Efficacy	3	adalimumab
rs1205	Efficacy	3	rosuvastatin	Coronary Disease
rs1417938	Efficacy	3	fenofibrate	Metabolic Syndrome
rs3091244	Efficacy	3	fenofibrate	Metabolic Syndrome

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1205	CRP	3	2.75	1	rosuvastatin
rs1130864	CRP	3	2.25	1	adalimumab
rs1417938	CRP	3	2.75	1	fenofibrate
rs3091244	CRP	3	4.50	1	fenofibrate
rs3093059	CRP		0.00	0
rs2794521	CRP		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Ethinyl Estradiol	affects cotreatment, increases expression, decreases reaction	7
Simvastatin	affects cotreatment, decreases expression, decreases reaction, increases expression, increases secretion (+1 more)	6
Atorvastatin	affects cotreatment, decreases expression, decreases reaction, increases expression	5
Resveratrol	decreases reaction, increases expression, increases secretion, decreases expression, increases abundance (+1 more)	4
Lipopolysaccharides	decreases reaction, increases expression, increases secretion	4
Quercetin	affects cotreatment, decreases reaction, increases expression, increases secretion, decreases expression	4
Particulate Matter	increases expression, increases secretion, decreases reaction	4
Rosiglitazone	decreases expression	3
Estradiol	affects expression, affects cotreatment, increases expression	3
Folic Acid	decreases expression, affects cotreatment	3
Niacin	affects cotreatment, increases reaction, decreases expression	3
Vitamin E	affects cotreatment, decreases expression	3
Vitamin B 6	affects cotreatment, decreases expression, affects expression	3
sodium arsenite	increases expression, increases secretion, decreases expression	2
ferrous sulfate	decreases expression	2
mono(2-ethyl-5-oxohexyl)phthalate	decreases expression	2
candesartan	decreases expression, increases reaction	2
ethinyl estradiol-desogestrel combination	increases expression, decreases reaction	2
Ezetimibe	decreases expression, increases reaction, affects cotreatment	2
Pamidronate	decreases expression, increases expression	2
Air Pollutants	increases expression	2
Vehicle Emissions	increases expression, decreases reaction	2
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	2
Diethylhexyl Phthalate	affects cotreatment, decreases expression, increases expression	2
Docosahexaenoic Acids	affects expression, affects cotreatment, decreases expression	2
Estrogens, Conjugated (USP)	decreases reaction, affects cotreatment, increases expression, decreases expression	2
Nitrogen Dioxide	increases expression	2
Fenofibrate	decreases expression, increases reaction	2
Zinc	affects cotreatment, increases expression, decreases expression	2
Medroxyprogesterone Acetate	affects cotreatment, increases expression	2

Clinical trials (associated diseases)

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