APCS

Summary

APCS (amyloid P component, serum, HGNC:584) is a protein-coding gene on chromosome 1q23.2, encoding Serum amyloid P-component (P02743). Can interact with DNA and histones and may scavenge nuclear material released from damaged circulating cells.

The protein encoded by this gene is a glycoprotein, belonging to the pentraxin family of proteins, which has a characteristic pentameric organization. These family members have considerable sequence homology which is thought to be the result of gene duplication. The binding of the encoded protein to proteins in the pathological amyloid cross-beta fold suggests its possible role as a chaperone. This protein is also thought to control the degradation of chromatin. It has been demonstrated that this protein binds to apoptotic cells at an early stage, which raises the possibility that it is involved in dealing with apoptotic cells in vivo.

Source: NCBI Gene 325 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 35 total
• GTEx eGene: eQTL in 1 tissue, sQTL in 0 (q < 0.05)
• Drug target: yes — 2 curated mechanism-of-action drugs
• Constraint (gnomAD): pLI 0.02 (LoF-tolerant), LOEUF 1.83 (unconstrained)
• MANE Select transcript: NM_001639

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:584
Approved symbol	APCS
Name	amyloid P component, serum
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Aliases	SAP, PTX2, MGC88159
Ensembl gene	ENSG00000132703
Ensembl biotype	protein_coding
OMIM	104770
Entrez	325

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

MANE Select: ENST00000255040

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000255040, ENST00001101201, ENST00001120249, ENST00001120250, ENST00001143715

RefSeq mRNA: 1 — MANE Select: NM_001639 NM_001639

CCDS: CCDS1186

Canonical transcript exons

ENST00000255040 — 2 exons

Exon	Start	End
ENSE00000904938	159587826	159587985
ENSE00000904939	159588101	159588865

Expression profiles

Bgee: expression breadth ubiquitous, 112 present calls, max score 99.80.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 7.2212 / max 4060.4852, expressed in 17 samples.

Highest expression (Bgee): lobe of liver, liver, gall bladder, islet of Langerhans, pancreas.

Genetic regulation across tissues (GTEx eQTL / sQTL)

APCS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 1 tissue and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

1 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	9.8e-10	+0.36	1:159609743:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
5978	7.2212	17

Top tissues by expression

showing 100 of 270 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.80	gold quality
liver	UBERON:0002107	98.37	gold quality
gall bladder	UBERON:0002110	94.20	gold quality
islet of Langerhans	UBERON:0000006	87.86	gold quality
pancreas	UBERON:0001264	76.70	gold quality
pancreatic ductal cell	CL:0002079	76.53	silver quality
epithelial cell of pancreas	CL:0000083	76.52	gold quality
body of pancreas	UBERON:0001150	73.45	gold quality
buccal mucosa cell	CL:0002336	70.77	gold quality
tendon of biceps brachii	UBERON:0008188	64.85	gold quality
oocyte	CL:0000023	57.53	gold quality
ileal mucosa	UBERON:0000331	57.21	silver quality
cartilage tissue	UBERON:0002418	54.96	gold quality
colonic epithelium	UBERON:0000397	54.95	silver quality
deltoid	UBERON:0001476	54.45	silver quality
metanephros cortex	UBERON:0010533	53.50	gold quality
quadriceps femoris	UBERON:0001377	52.45	gold quality
upper leg skin	UBERON:0004262	52.30	gold quality
metanephros	UBERON:0000081	52.08	gold quality
vastus lateralis	UBERON:0001379	51.40	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
adult mammalian kidney	UBERON:0000082	50.19	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
thymus	UBERON:0002370	49.33	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
kidney	UBERON:0002113	48.35	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
oviduct epithelium	UBERON:0004804	48.21	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.74	gold quality
nasal cavity epithelium	UBERON:0005384	47.70	gold quality
skin of hip	UBERON:0001554	47.66	silver quality
renal glomerulus	UBERON:0000074	47.60	gold quality
layer of synovial tissue	UBERON:0007616	47.54	gold quality
kidney epithelium	UBERON:0004819	47.32	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
diaphragm	UBERON:0001103	47.05	gold quality
gluteal muscle	UBERON:0002000	47.03	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
muscle tissue	UBERON:0002385	47.00	gold quality
nephron tubule	UBERON:0001231	46.88	gold quality
endometrium epithelium	UBERON:0004811	46.85	gold quality
cranial nerve II	UBERON:0000941	46.81	silver quality
heart right ventricle	UBERON:0002080	46.78	gold quality
skeletal muscle tissue	UBERON:0001134	46.36	gold quality
epithelium of esophagus	UBERON:0001976	46.11	gold quality
squamous epithelium	UBERON:0006914	45.68	gold quality
cortex of kidney	UBERON:0001225	45.51	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
esophagus squamous epithelium	UBERON:0006920	44.27	gold quality
uterine cervix	UBERON:0000002	44.23	gold quality
pharyngeal mucosa	UBERON:0000355	43.99	gold quality
ectocervix	UBERON:0012249	43.64	gold quality
trachea	UBERON:0003126	43.44	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
epithelium of bronchus	UBERON:0002031	43.30	gold quality
bronchus	UBERON:0002185	43.16	gold quality
gingiva	UBERON:0001828	42.99	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
descending thoracic aorta	UBERON:0002345	42.51	gold quality
substantia nigra pars reticulata	UBERON:0001966	42.48	gold quality
medulla oblongata	UBERON:0001896	41.74	gold quality
Brodmann (1909) area 23	UBERON:0013554	41.74	gold quality
medial globus pallidus	UBERON:0002477	41.59	gold quality
epithelium of mammary gland	UBERON:0003244	41.50	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
dorsal plus ventral thalamus	UBERON:0001897	41.20	gold quality
parotid gland	UBERON:0001831	41.12	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
globus pallidus	UBERON:0001875	41.08	gold quality
placenta	UBERON:0001987	41.08	gold quality
right coronary artery	UBERON:0001625	41.00	silver quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
duodenum	UBERON:0002114	40.74	silver quality
blood	UBERON:0000178	40.73	gold quality
mucosa of sigmoid colon	UBERON:0004993	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
urinary bladder	UBERON:0001255	40.56	gold quality
dorsal root ganglion	UBERON:0000044	40.51	gold quality
pleura	UBERON:0000977	40.46	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-9	yes	2976.50
E-MTAB-8495	yes	1532.91
E-MTAB-10553	yes	34.19
E-GEOD-83139	yes	11.31
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enriched

37 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	3389.4	not detected
Gallbladder	tissue	44.8	not detected
Olfactory bulb	tissue	4.3
Cerebellum	tissue	4.2	not detected
Corpus callosum	tissue	3.9
Cerebral cortex	tissue	3.4	not detected
Insular cortex	tissue	3.4
Retrosplenial and cingulate cortex	tissue	3.3
Amygdala	tissue	3.2
Ventral forebrain	tissue	3.1
Retrosplenial cortex	tissue	3.1
Temporal cortex	tissue	3.1
Basal ganglia	tissue	3.0	not detected
Prefrontal cortex	tissue	2.9
Hippocampal formation	tissue	2.9
Entorhinal cortex	tissue	2.9
Occipital cortex	tissue	2.8
Putamen	tissue	2.7
Septum	tissue	2.7
Periaqueductal gray	tissue	2.6
Motor cortex	tissue	2.5
Spinal cord	tissue	2.5
Hypothalamus	tissue	2.4
Substantia nigra	tissue	2.4
Somatosensory cortex	tissue	2.4
Midbrain	tissue	2.2
Medulla oblongata	tissue	2.2
Thalamus	tissue	1.8
Superior colliculi	tissue	1.8
Pons	tissue	1.6
Kidney	tissue	1.1	not detected
Pancreas	tissue	0.5	not detected
Stomach 1	tissue	0.2	not detected
Retina	tissue	0.2
Adipose tissue	tissue	0.2	not detected
Placenta	tissue	0.1	not detected
Testis	tissue	0.0	high

Brain sub-regions (HPA Brain Atlas): detected in 7; highest nTPM — White matter (3.9), Dorsal hippocampus (2.6), Subiculum (2.6), Ventral hippocampus (2.6), Dorsal spinal cord (2.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, STAT3, TP53

miRNA regulators (miRDB)

Targeting APCS by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

13 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-4423-3P	97.98	69.66	912
HSA-MIR-558	97.50	67.16	977
HSA-MIR-3156-5P	96.93	67.36	800

Functional genomics

gnomAD constraint: pLI 0.0208, LOEUF 1.83, missense Z -0.687 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000255040 — one region, missense o/e 1.17.

Literature-anchored findings (GeneRIF, showing 40)

• Serum amyloid P binds to cells in the early stage of apoptosis, presumably via phosphatidylethanolamine exposed in flip-flopped membranes, suggesting a role for serum amyloid P in the clearance of these cells in vivo. (PMID:11441067)
• A possible role of SAP in either host resistance or viral virulence was investigated during influenza infection in vivo. Influenza virus infection is not affected by serum amyloid P component.Human SAP binds much more avidly than mouse SAP to the virus. (PMID:11984001)
• Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. (PMID:12015594)
• serum amyloid P component does not circulate in complex with C4-binding protein, fibronectin or any other major protein ligand (PMID:12100475)
• structures of crystalline complexes of human serum amyloid P component with its carbohydrate ligand, the cyclic pyruvate acetal of galactose (PMID:12126626)
• Serum amyloid p component binds to late apoptotic cells and is involved in the phagocytosis of these cells by human monocyte-derived macrophages. (PMID:12528126)
• Serum amyloid P component binding to Shiga toxin 2 requires both a subunit and B pentamer. (PMID:14500533)
• Purified SAP inhibits fibrocyte differentiation at levels similar to those found in plasma, while depleting SAP reduces the ability of plasma to inhibit fibrocyte differentiation. (PMID:14607961)
• This protein, a non-fibrillar component, causes soluble fibrils to condense into localized fibrillar aggregates with a greatly enhanced local density of fibril entanglements. (PMID:15031287)
• Genetic variation in APCS is associated with amyloid polyneuropathy (PMID:15649951)
• Amyloid-associated SAP significantly increases fibrillar prion protein-related peptide-induced release of interleukin-6 and TNF-alpha from human microglia. (PMID:15837583)
• Review discusses clinical significance of different levels of SAP, its role in induction or protection from autoimmunity, and the presence of specific SAP autoantibodies in different autoimmune diseases. (PMID:16380821)
• the shared specificity as well as their shared capability to activate complement, suggest that IgM and the pentraxins CRP and SAP exert similar functions in the removal of apoptotic cells (PMID:16643876)
• Monocytes bound biotinylated serum amyloid P component with avidity in a dose-dependent and saturable manner; speculated that binding of SAP by monocytes could be of physiological relevance at extravascular sites by influencing complement regulation (PMID:16784490)
• Serum amyloid P (SAP) and C-reactive protein (CRP) may represent different facets of inflammation. The association of SAP with cardiovascular disease in these older adults further supports the role of innate immunity in atherosclerosis. (PMID:17138933)
• No reduced circulating concentrations of serum amyloid P component (SAP) in patients with systemic sclerosis, nor any evidence of an association between SAP levels and the extent or severity of fibrosis were observed. (PMID:17530641)
• SAP may modulate the inflammatory response to amyloid fibrils in atherosclerosis (PMID:17630380)
• SAP was quantitated using PVDF affinity probes and MALDI-MS. (PMID:17676666)
• The complex structure between human SAP and FcgammaRIIa reveals a diagonally bound receptor on each SAP pentamer with both D1 and D2 domains of the receptor contacting the ridge helices from two SAP subunits. (PMID:19011614)
• Our data suggest that measurement of cerebrospinal fluid SAP levels can aid in the identification of incipient Alzheimer’s disease among mild cognitive impairment patients (PMID:19052452)
• Functional analysis demonstrated that SAP associated with HDL promotes SR-BI-dependent cholesterol efflux and lipid-free SAP enhances ABCA1-dependent cholesterol efflux (PMID:20189569)
• SAP has an effect on macrophages in fibrotic lung disease (PMID:20300636)
• these data suggest that local production of serum amyloid P and c-reactive protein in the alzheimer disease brain does not substantially contribute to the CSF levels. (PMID:20930309)
• serum SAP levels may be an easy detected predictor for the healing of burn wounds (PMID:20932823)
• TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P. (PMID:21044893)
• Interaction between MBL and PTX3 led to communication between the lectin and classical complement pathways via recruitment of C1q, whereas SAP-enhanced complement activation occurs via a hitherto unknown mechanism (PMID:21106539)
• Serum amyloid P level increased by approximately 5-fold in Parkinson’s disease samples;a potential feasibility of plasma amyloid P as a marker to approach Parkinson’s disease (PMID:21223953)
• Human SAP inhibits DNA-mediated innate immune activation in vitro and may limit innate and adaptive immune responses after DNA vaccination of transgenic mice. (PMID:21278351)
• Under physiological conditions, phosphoethanolamine is bound with higher affinity by human SAP than by human CRP. (PMID:21360619)
• Low levels of serum amyloid P mark the brains of individuals who escape dementia despite the presence of beta amyloid plaques and tangles in Alzheimer’s disease neuropathology. (PMID:22205573)
• The START domain in GPBP is important for this interaction. SAP and GPBP form complexes in blood and partly colocalize in amyloid plaques from Alzheimer disease patients. (PMID:22396542)
• observations suggest that serum amyloid P, at least in part, uses FcgammaRI and FcRgamma to inhibit fibrocyte differentiation (PMID:22493081)
• Studies indicate that pharmaceutical grade serum amyloid P component and C-reactive protein were isolated and purified. (PMID:22867744)
• 9 different proteins (haptoglobin, transthyretin, apolipoprotein A-1, serum amyloid P component, apolipoprotein E, complement factor H, fibrinogen gamma, thrombin, complement C3) were identified as a potential diagnostic pattern of Parkinson’s disease. (PMID:23385359)
• SAP has a new role in reducing the toxicity of early amyloidogenic aggregates in transthyretin amiloidosis. (PMID:23390551)
• Persons who develop non-affective psychoses have lower levels of certain acute phase proteins, including SAP, at the time of birth. (PMID:23423137)
• [review] On the basis of structure, serum amyloid P component is a prototype of the short pentraxin family. (PMID:23527487)
• SAP may act as an effective receptor mimic to limit influenza A virus infection of airway epithelial cells. (PMID:23544079)
• Human SAP binds phosphoethanolamine, while rabbits seem to have low levels of SAP that bind to a lesser extent. (PMID:23600950)
• These results indicate that SAP functions as a host defense factor, similar to other peptidoglycan recognition proteins and nucleotide-binding oligomerization domain-like receptors. (PMID:23966633)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	apcs	ENSDARG00000045089
mus_musculus	Apcs	ENSMUSG00000026542
rattus_norvegicus	Apcs	ENSRNOG00000009086

Paralogs (5): NPTX2 (ENSG00000106236), CRP (ENSG00000132693), PTX3 (ENSG00000163661), NPTX1 (ENSG00000171246), PTX4 (ENSG00000251692)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98229) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased autoantibody level	2
amyloidosis	1
abnormal spleen morphology	1
abnormal kidney morphology	1
abnormal spleen red pulp morphology	1
abnormal spleen white pulp morphology	1
decreased susceptibility to bacterial infection	1
glomerulonephritis	1
increased spleen white pulp amount	1
decreased susceptibility to endotoxin shock	1
increased susceptibility to bacterial infection induced morbidity/mortality	1
decreased susceptibility to bacterial infection induced morbidity/mortality	1
renal glomerular immunoglobulin deposits	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Mesocricetus auratus	P07629	82.9%	Diamond
Nothocricetulus migratorius	P15697	82.9%	Diamond
Sus scrofa	O19063	79.0%	Diamond
Bos taurus	Q3T004	79.0%	Diamond
Oryctolagus cuniculus	P02742	74.2%	Diamond
Cavia porcellus	P49254	73.3%	Diamond
Xenopus laevis	P49263	49.6%	Diamond
Lepidobatrachus laevis	Q9PTT2	49.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CRP	protein-coding	1401
LINC02819	ncRNA	105371462
OR10J5	protein-coding	127385

Protein

Protein identifiers

Serum amyloid P-component — P02743 (reviewed: P02743)

Alternative names: 9.5S alpha-1-glycoprotein

All UniProt accessions (2): P02743, V9HWP0

UniProt curated annotations — full annotation on UniProt →

Function. Can interact with DNA and histones and may scavenge nuclear material released from damaged circulating cells. May also function as a calcium-dependent lectin.

Subunit / interactions. Homopentamer. Pentraxin (or pentaxin) have a discoid arrangement of 5 non-covalently bound subunits.

Subcellular location. Secreted.

Tissue specificity. Found in serum and urine.

Post-translational modifications. N-glycosylated with a complex biantennary oligosaccharide chain with a sialic acid at the end (disialo-SAP). Monosialo-SAP as well as asioalo-SAP are also detected.

Disease relevance. SAP is a precursor of amyloid component P which is found in basement membrane and associated with amyloid deposits.

Cofactor. Binds 2 calcium ions per subunit.

Similarity. Belongs to the pentraxin family.

RefSeq proteins (1): NP_001630* (*=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 (40 total): strand 15, binding site 8, helix 6, sequence variant 3, chain 2, signal peptide 1, glycosylation site 1, disulfide bond 1, sequence conflict 1, turn 1, domain 1

Structure

Experimental structures (PDB)

13 structures by resolution:

PDB	Title	Method	Resolution (Å)
4AVS	Structure of N-Acetyl-L-Proline bound to Serum Amyloid P Component	X-RAY DIFFRACTION	1.4
3KQR	The structure of serum amyloid p component bound to phosphoethanolamine	X-RAY DIFFRACTION	1.5
4AYU	Structure of N-Acetyl-D-Proline bound to serum amyloid P component	X-RAY DIFFRACTION	1.5
4AVV	Structure of CPHPC bound to Serum Amyloid P Component	X-RAY DIFFRACTION	1.6
2W08	The structure of serum amyloid P component bound to 0-phospho- threonine	X-RAY DIFFRACTION	1.7
1SAC	THE STRUCTURE OF PENTAMERIC HUMAN SERUM AMYLOID P COMPONENT	X-RAY DIFFRACTION	2
2A3Y	Pentameric crystal structure of human serum amyloid P-component bound to …	X-RAY DIFFRACTION	2
1GYK	Serum Amyloid P Component co-crystallised with MOBDG at neutral pH	X-RAY DIFFRACTION	2.2
2A3W	Decameric structure of human serum amyloid P-component bound to …	X-RAY DIFFRACTION	2.2
1LGN	DECAMERIC DAMP COMPLEX OF HUMAN SERUM AMYLOID P COMPONENT	X-RAY DIFFRACTION	2.8
3D5O	Structural recognition and functional activation of FcrR by innate pentraxins	X-RAY DIFFRACTION	2.8
2A3X	Decameric crystal structure of human serum amyloid P-component bound to …	X-RAY DIFFRACTION	3
4AVT	Structure of CPHPC bound to Serum Amyloid P Component	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02743-F1	94.48	0.91

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted secreted proteins, Plasma proteins, Disease related genes, Potential drug targets

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH supported

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)

Position	Role
157	Ca(2+)
167	Ca(2+)
77	Ca(2+)
78	Ca(2+)
155	Ca(2+)
156	Ca(2+)

Disulfide bonds (1)

Type	Positions
Disulfide bond	55–114

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	51

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 2; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

2 pathways:

ID	Pathway	Evidence
R-HSA-977225	Amyloid fiber formation	curated
R-HSA-392499	Metabolism of proteins	—

MSigDB gene sets: 154 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_INFLAMMATORY_RESPONSE, GNF2_GSTM1, GNF2_HPN, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_CHAPERONE_MEDIATED_PROTEIN_COMPLEX_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_ACUTE_INFLAMMATORY_RESPONSE, GOBP_HOST_MEDIATED_PERTURBATION_OF_VIRAL_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_REGULATION_OF_ACUTE_INFLAMMATORY_RESPONSE, GOBP_WOUND_HEALING

GO Biological Process (11): negative regulation of acute inflammatory response (GO:0002674), protein folding (GO:0006457), acute-phase response (GO:0006953), negative regulation by host of viral glycoprotein metabolic process (GO:0044871), innate immune response (GO:0045087), negative regulation of monocyte differentiation (GO:0045656), host-mediated suppression of symbiont invasion (GO:0046597), negative regulation of viral process (GO:0048525), chaperone-mediated protein complex assembly (GO:0051131), negative regulation of wound healing (GO:0061045), negative regulation of glycoprotein metabolic process (GO:1903019)

GO Molecular Function (7): complement component C1q complex binding (GO:0001849), calcium ion binding (GO:0005509), carbohydrate binding (GO:0030246), identical protein binding (GO:0042802), virion binding (GO:0046790), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): extracellular region (GO:0005576), nucleus (GO:0005634), extracellular exosome (GO:0070062), blood microparticle (GO:0072562)

Reactome top-level categories

1 top-level categories:

Category	Pathways
Metabolism of proteins	1

GO top-level categories

38 GO namespaces:

Category	Terms
acute inflammatory response	2
glycoprotein metabolic process	2
binding	2
protein binding	2
cellular anatomical structure	2
regulation of acute inflammatory response	1
negative regulation of inflammatory response	1
cellular process	1
protein maturation	1
host-mediated suppression of viral proces	1
modulation by host of viral glycoprotein metabolic process	1
negative regulation of viral process	1
negative regulation of glycoprotein metabolic process	1
immune response	1
defense response to symbiont	1
negative regulation of myeloid leukocyte differentiation	1
monocyte differentiation	1
regulation of monocyte differentiation	1
innate immune response	1
host-mediated perturbation of symbiont process	1
viral process	1
negative regulation of biological process	1
regulation of viral process	1
protein-containing complex assembly	1
negative regulation of response to external stimulus	1
wound healing	1
regulation of wound healing	1
negative regulation of response to wounding	1
negative regulation of protein metabolic process	1
regulation of glycoprotein metabolic process	1
opsonin binding	1
complement binding	1
protein-containing complex binding	1
metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1
extracellular region	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 14 of 24 annotations. The rest are phylogenetic / computational / electronic (IEA).

14 experimentally-supported GO terms:

GO term	NS	Evidence
host-mediated suppression of symbiont invasion	BP	direct assay
innate immune response	BP	direct assay
negative regulation by host of viral glycoprotein metabolic process	BP	direct assay
negative regulation of glycoprotein metabolic process	BP	direct assay
negative regulation of monocyte differentiation	BP	direct assay
negative regulation of viral process	BP	direct assay
blood microparticle	CC	high-throughput assay
extracellular exosome	CC	high-throughput assay
extracellular region	CC	high-throughput assay
nucleus	CC	high-throughput assay
calcium ion binding	MF	direct assay
complement component C1q complex binding	MF	direct assay
identical protein binding	MF	physical interaction
virion binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,052 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APCS	TTR	P02766	787
APCS	SAA1	P02735	725
APCS	SAA1	P02735	724
APCS	CREB3L3	Q68CJ9	681
APCS	OCA2	Q04671	676
APCS	RBP4	P02753	663
APCS	IFI16	Q16666	626
APCS	IL6	P05231	600
APCS	FGG	P02679	568
APCS	C1S	P09871	567
APCS	FGB	P02675	564
APCS	APOE	P02649	547
APCS	SPTA1	P02549	547
APCS	APOA4	P06727	540
APCS	APOA1	P02647	538

IntAct

Human interaction partners of APCS in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

9 partners by confidence:

Partner	Interaction type	MIscore	Records
CERT1	direct interaction	0.620	12
ALX1	physical association	0.560	3
APP	physical association	0.560	3
MBL2	physical association	0.400	2
COPS5	physical association	0.370	1
GK	physical association	0.370	1
GOT2	physical association	0.370	1
HES1	physical association	0.370	1
GRB2	physical association	0.000	1

BioGRID (36 interactions; top human partners by supporting records): C4BPA (Co-purification; 2 records), CTSB (Affinity Capture-MS; 2 records), AGPAT1 (Affinity Capture-MS), ALX1 (Two-hybrid), APP (Affinity Capture-Western), CALU (Reconstituted Complex), CCR1 (Affinity Capture-MS), COPS5 (Two-hybrid), CRP (Reconstituted Complex), FCGR1A (Reconstituted Complex), FCGR3A (Reconstituted Complex), FCGR3B (Reconstituted Complex), FN1 (Affinity Capture-Western), GK (Two-hybrid), GNG8 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for APCS: 35 ClinVar records (0 pathogenic / likely pathogenic); 5 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	6
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 18 predictions of 27):

Position(s)	Effect	Δscore	Sites
1:159587986–159587987	donor_loss	0.9900	5
1:159588099–159588100	acceptor_loss	0.9700	5
1:159588100	acceptor_loss	0.9600
1:159588093	acceptor_gain	0.9300
1:159588096	acceptor_gain	0.9200
1:159588098	acceptor_loss	0.7000
1:159587987	donor_loss	0.6800
1:159588611	acceptor_gain	0.6300
1:159587985	donor_gain	0.5300
1:159587985	donor_gain	0.5000

AlphaMissense

334 missense substitutions predicted likely pathogenic (of 1,449 scored), across 104 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F30	8	0.878	0.974
F69	8	0.809	0.944
W117	7	0.896	0.967
C55	7	0.884	0.927
C114	7	0.868	0.909
F163	7	0.865	0.962
W204	7	0.839	0.943
W179	7	0.830	0.949
F169	7	0.800	0.872
D157	7	0.750	0.848
G153	5	0.889	0.913
S60	5	0.866	0.957
G171	5	0.848	0.909
Y90	5	0.812	0.898
F28	5	0.800	0.892
F52	5	0.799	0.890
K84	5	0.790	0.931
W127	5	0.786	0.859
G122	5	0.782	0.874
G213	5	0.771	0.896

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	favorable	1.23e-06
Pancreatic Adenocarcinoma (validation)	unfavorable	1.18e-05

Disease associations

OMIM: gene MIM:104770 | disease phenotypes:

GWAS associations

5 associations:

Study	Trait	p-value
GCST001650_8	C-reactive protein	4e-73
GCST001650_1	C-reactive protein	1e-37
GCST006585_1757	Blood protein levels	2e-27
GCST001650_11	C-reactive protein	3e-10
GCST011780_2	Neonatal white matter microstructure	8e-8

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0005674	white matter microstructure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4929 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the APCS protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

2 curated-mechanism drugs:

Drug	Modality	Max phase
DEZAMIZUMAB	Antibody	2
MIRIDESAP	Small molecule	2

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — Serum pentraxins

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
miridesap	Binding	6.05	pIC50

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
Cyclosporine	decreases expression	2
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
titanium dioxide	decreases expression	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Valsartan	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Troglitazone	decreases expression	1
Acetaminophen	decreases expression	1
Gemcitabine	decreases expression	1
Arsenic	affects methylation	1
Cadmium	affects binding	1
Cocaine	increases expression	1
Copper	affects binding	1
Estradiol	decreases expression	1
Heparin	increases expression	1
Lead	affects binding	1
Lipopolysaccharides	increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Nickel	affects binding	1
Ozone	increases expression, increases abundance	1
Tamoxifen	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Zinc	affects binding	1
Okadaic Acid	decreases expression	1
Soot	increases abundance, increases expression	1

ChEMBL screening assays

21 unique, capped per target: 21 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3882249	Binding	Inhibition of serum amyloid P-component (unknown origin) binding to immobilized amyloid beta 1 to 42 fibrils at 500 umol/L in presence of calcium by surface plasma resonance	Compounds inhibiting the binding of sap for treating osteoarthritis

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.