SAA2

Summary

SAA2 (serum amyloid A2, HGNC:10514) is a protein-coding gene on chromosome 11p15.1, encoding Serum amyloid A-2 protein (P0DJI9). Major acute phase reactant.

This gene encodes a member of the serum amyloid A family of apolipoproteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a major acute phase protein that is highly expressed in response to inflammation and tissue injury. This protein also plays an important role in HDL metabolism and cholesterol homeostasis. High levels of this protein are associated with chronic inflammatory diseases including atherosclerosis, rheumatoid arthritis, Alzheimer’s disease and Crohn’s disease. This protein may also be a potential biomarker for certain tumors. Finally, antimicrobial activity against S. aureus and E. coli resides in the N-terminal portion of the mature protein.

Source: NCBI Gene 6289 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 10 total
• MANE Select transcript: NM_030754

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10514
Approved symbol	SAA2
Name	serum amyloid A2
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000134339
Ensembl biotype	protein_coding
OMIM	104751
Entrez	6289

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000256733, ENST00000414546, ENST00000526900, ENST00000528349, ENST00000529528, ENST00000530400, ENST00000949286, ENST00000949287

RefSeq mRNA: 9 — MANE Select: NM_030754 NM_001127380, NM_001385666, NM_001385667, NM_001385668, NM_001385669, NM_001385670, NM_001385671, NM_001385672, NM_030754

CCDS: CCDS44548, CCDS7833

Canonical transcript exons

ENST00000256733 — 4 exons

Exon	Start	End
ENSE00000000273	18248603	18248668
ENSE00002143722	18245240	18245515
ENSE00003628183	18245910	18246048
ENSE00003685058	18247921	18248015

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 98.41.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1502 / max 131.9106, expressed in 5 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118920	0.1470	21
118916	0.0492	4
118918	0.0415	4
118919	0.0350	5
118917	0.0244	4
118921	0.0194	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.41	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.23	gold quality
saliva-secreting gland	UBERON:0001044	96.19	gold quality
minor salivary gland	UBERON:0001830	96.05	gold quality
liver	UBERON:0002107	95.91	gold quality
thoracic mammary gland	UBERON:0005200	93.46	gold quality
mammary gland	UBERON:0001911	93.45	gold quality
omental fat pad	UBERON:0010414	93.33	gold quality
vermiform appendix	UBERON:0001154	92.00	gold quality
adipose tissue	UBERON:0001013	89.49	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.98	gold quality
right adrenal gland cortex	UBERON:0035827	84.60	gold quality
right adrenal gland	UBERON:0001233	84.45	gold quality
left uterine tube	UBERON:0001303	84.38	gold quality
gastrocnemius	UBERON:0001388	84.00	gold quality
left coronary artery	UBERON:0001626	82.57	gold quality
descending thoracic aorta	UBERON:0002345	81.04	gold quality
adenohypophysis	UBERON:0002196	80.25	gold quality
gall bladder	UBERON:0002110	79.74	gold quality
thoracic aorta	UBERON:0001515	79.61	gold quality
mucosa of stomach	UBERON:0001199	79.55	gold quality
ascending aorta	UBERON:0001496	79.46	gold quality
tonsil	UBERON:0002372	79.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.04	silver quality
left adrenal gland	UBERON:0001234	78.97	gold quality
muscle of leg	UBERON:0001383	78.09	gold quality
skeletal muscle organ	UBERON:0014892	77.48	gold quality
left adrenal gland cortex	UBERON:0035825	77.44	gold quality
adrenal gland	UBERON:0002369	76.93	gold quality
esophagus mucosa	UBERON:0002469	76.43	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-HCAD-9	yes	57590.07
E-GEOD-130473	yes	19150.94
E-MTAB-9841	yes	1751.04
E-MTAB-10283	yes	1738.40
E-MTAB-8559	yes	955.65
E-GEOD-86618	yes	541.99
E-CURD-114	yes	29.47
E-HCAD-1	yes	16.12
E-MTAB-7249	yes	11.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF5, CEBPA, CEBPB, CEBPD, DDRGK1, NFKB1, NFKB2, NFKB, REL, RELA, TCF3

miRNA regulators (miRDB)

8 targeting SAA2, 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-3065-5P	99.97	71.56	3281
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-4638-3P	97.90	65.75	905
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-759	96.16	66.77	873

Literature-anchored findings (GeneRIF, showing 13)

• The glucocorticoid response element of the SAA2 promoter is dysfunctional compared to that of SAA1, hence glucocorticoids are unable to enhance the cytokine-driven transcriptional activity of SAA2. (PMID:12077270)
• saa2 is regulated by tumor necrosis factor-alpha, interleukin-6, and glucocorticoids in hepatic and epithelial cells. (PMID:14871291)
• SAA1a/a genotype is one genetic factor that confers a significant risk for amyloidosis in the Turkish FMF population but neither SAA1 nor SAA2 genotypes had a significant effect on SAA level. (PMID:15170927)
• Increased expression of SAA2 by adipocytes in obesity may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities. (PMID:16737350)
• CRP and SAA strongly correlated up to the fifth day of observation but were not good predictors of mortality in septic shock. (PMID:18385816)
• Data show that both rs12218 of the SAA1 gene and rs2468844 of SAA2 gene are associated with carotid IMT in healthy Han Chinese subjects. (PMID:21103356)
• successful quantification of SAA2 in crude serum by MRM, for the first time, shows that SAA2 can be a good biomarker for the detection of lung cancers. (PMID:22300576)
• Pathogenic serum amyloid A 1.1 shows a long oligomer-rich fibrillation lag phase contrary to the highly amyloidogenic non-pathogenic SAA2.2 (PMID:23223242)
• The prevalence of the SAA2 polymorphisms (rs 2445174 and rs2468844) did not differ significantly between the groups of ankylosing spondylitis patients with and without amyloidosis. (PMID:26300108)
• after stimulation by various pro-inflammatory conditions, changes in SAA1, SAA2 and SAA4 gene expression at both the transcriptional and protein levels were evaluated during maturation of freshly collected human monocytes into macrophages. (PMID:31100086)
• SAA2 displays antimicrobial activity against S. aureus and E. coli. (PMID:31819008)
• Serum amyloid A is a soluble pattern recognition receptor that drives type 2 immunity. (PMID:32572240)
• Elevated expression of interleukin-6 (IL-6) and serum amyloid A (SAA) in the skin and the serum of recessive dystrophic epidermolysis bullosa: Skin as a possible source of IL-6 through Toll-like receptor ligands and SAA. (PMID:38429888)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	saa	ENSDARG00000045999
drosophila_melanogaster	CG30467	FBGN0050467

Paralogs (3): SAA4 (ENSG00000148965), SAAL1 (ENSG00000166788), SAA1 (ENSG00000173432)

Protein

Protein identifiers

Serum amyloid A-2 protein — P0DJI9 (reviewed: P0DJI9)

All UniProt accessions (3): P0DJI9, E9PR14, G3V1D9

UniProt curated annotations — full annotation on UniProt →

Function. Major acute phase reactant.

Subunit / interactions. Apolipoprotein of the HDL complex.

Subcellular location. Secreted.

Tissue specificity. Expressed by the liver; secreted in plasma.

Disease relevance. Reactive, secondary amyloidosis is characterized by the extracellular accumulation in various tissues of the SAA2 protein. These deposits are highly insoluble and resistant to proteolysis; they disrupt tissue structure and compromise function.

Induction. Upon cytokine stimulation.

Polymorphism. At least 2 different SAA2 alleles have been described: SAA2.1 (SAA2alpha) and SAA2.2 (SAA2beta). We use here the revised nomenclature described in PubMed:10211414. The sequence shown is that of SAA2.2.

Similarity. Belongs to the SAA family.

Isoforms (2)

UniProt ID	Names	Canonical?
P0DJI9-1	1	yes
P0DJI9-2	2

RefSeq proteins (9): NP_001120852, NP_001372595, NP_001372596, NP_001372597, NP_001372598, NP_001372599, NP_001372600, NP_001372601, NP_110381* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000096	Serum_amyloid_A	Family
IPR052464	Synovial_Prolif_Regulator	Family

Pfam: PF00277

UniProt features (7 total): chain 2, signal peptide 1, region of interest 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DJI9-F1	94.01	0.78

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 74 (showing top): GOBP_INFLAMMATORY_RESPONSE, WONG_ENDMETRIUM_CANCER_UP, GOBP_ACUTE_PHASE_RESPONSE, GOCC_HIGH_DENSITY_LIPOPROTEIN_PARTICLE, GOCC_PROTEIN_LIPID_COMPLEX, FEVR_CTNNB1_TARGETS_UP, KRIEG_KDM3A_TARGETS_NOT_HYPOXIA, GUILLAUMOND_KLF10_TARGETS_UP, AKT_UP_MTOR_DN.V1_UP, AKT_UP.V1_UP, PKCA_DN.V1_DN, ZNF274_TARGET_GENES, MIR511_5P, MIR2052, MIR7977

GO Biological Process (1): acute-phase response (GO:0006953)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): high-density lipoprotein particle (GO:0034364), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
acute inflammatory response	1
binding	1
plasma lipoprotein particle	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

12 interactions, top by confidence:

A	B	Type	Score
SAA2	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
TEAD2	SAA2	psi-mi:“MI:0915”(physical association)	0.490
SAA2	TEAD2	psi-mi:“MI:0915”(physical association)	0.490
SAA1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TIMM10	IGLL5	psi-mi:“MI:0914”(association)	0.350
UBE2U	IGLL5	psi-mi:“MI:0914”(association)	0.350
SAA1	SEMG1	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
SAA2	CIDEB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): SAA2 (Two-hybrid), CIDEB (Two-hybrid), SAA2 (Affinity Capture-MS), SAA2 (Affinity Capture-MS), SAA2 (Affinity Capture-MS), SAA2 (Two-hybrid), SAA2 (Negative Genetic), APOA2 (Cross-Linking-MS (XL-MS)), SAA2 (Cross-Linking-MS (XL-MS)), SAA2 (Cross-Linking-MS (XL-MS)), APOD (Cross-Linking-MS (XL-MS)), SAA2 (Cross-Linking-MS (XL-MS)), APOA1 (Cross-Linking-MS (XL-MS)), SAA2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: B6HJA3, O56140, O89746, P02739, P02740, P04918, P05366, P05367, P09345, P09507, P0DJI8, P0DJI9, P0DSN9, P0DSO0, P11132, P11135, P18575, P19453, P19707, P19708, P19857, P20726, P20727, P22000, P35541, P35542, P35543, P42819, P53613, P53614, P81491, P87506, Q0CVD7, Q16625, Q2F4V2, Q32L76, Q6DEL2, Q6DPZ9, Q6DQ19, Q6DQ20

Diamond homologs: P02738, P02739, P02740, P04918, P05366, P05367, P0DJI8, P0DJI9, P0DSN9, P0DSO0, P18575, P19453, P19707, P19708, P19857, P20726, P20727, P22000, P31532, P35541, P35542, P35543, P42819, P53613, P53614, P81491, Q32L76, Q8SQ28

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

625 predictions. Top by Δscore:

Variant	Effect	Δscore
11:18246045:GCCC:G	acceptor_gain	1.0000
11:18246046:CCC:C	acceptor_gain	1.0000
11:18246046:CCCC:C	acceptor_gain	1.0000
11:18246047:CC:C	acceptor_gain	1.0000
11:18246047:CCC:C	acceptor_gain	1.0000
11:18246048:CC:C	acceptor_gain	1.0000
11:18246049:C:CC	acceptor_gain	1.0000
11:18246050:T:G	acceptor_loss	1.0000
11:18245513:TTG:T	acceptor_gain	0.9900
11:18245514:TG:T	acceptor_gain	0.9900
11:18245524:C:CT	acceptor_gain	0.9900
11:18245524:C:T	acceptor_gain	0.9900
11:18245525:A:T	acceptor_gain	0.9900
11:18245528:C:CT	acceptor_gain	0.9900
11:18245529:A:T	acceptor_gain	0.9900
11:18245532:C:CT	acceptor_gain	0.9900
11:18245533:A:T	acceptor_gain	0.9900
11:18245905:GTTA:G	donor_loss	0.9900
11:18245906:TTAC:T	donor_loss	0.9900
11:18245908:A:C	donor_loss	0.9900
11:18245909:C:CG	donor_loss	0.9900
11:18246044:AGCCC:A	acceptor_gain	0.9900
11:18246049:C:T	acceptor_gain	0.9900
11:18246049:CT:C	acceptor_loss	0.9900
11:18245511:CATTG:C	acceptor_gain	0.9800
11:18245514:TGC:T	acceptor_loss	0.9800
11:18245516:C:CC	acceptor_gain	0.9800
11:18245516:C:CG	acceptor_loss	0.9800
11:18245909:CCTGA:C	donor_gain	0.9800
11:18247838:T:TA	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000157604 (11:18246593 A>T), RS1000208051 (11:18246471 G>A,C,T), RS1000390383 (11:18240393 G>A), RS1000564520 (11:18242842 G>A,C), RS1000680297 (11:18240141 T>A,C), RS1001412130 (11:18237942 C>G,T), RS1001448013 (11:18247860 G>A,C,T), RS1001458594 (11:18244704 C>G), RS1001647257 (11:18244072 G>A,C), RS1001972062 (11:18244337 C>T), RS1002287420 (11:18245676 A>C,G), RS1002351085 (11:18239989 A>G), RS1002418144 (11:18239635 A>C,G), RS1002573045 (11:18250404 C>A), RS1003048837 (11:18249097 C>A,T)

Disease associations

OMIM: gene MIM:104751 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression	3
tofacitinib	decreases reaction, increases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
baricitinib	decreases reaction, increases expression	1
2,2’,3,4’,5,5’,6-heptachlorobiphenyl	decreases expression	1
bisphenol F	decreases expression	1
methyleugenol	decreases expression	1
propionaldehyde	increases expression	1
propylparaben	increases expression	1
bisphenol A	increases expression	1
lead acetate	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
methylparaben	decreases expression, increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
cupric chloride	decreases expression	1
perfluorodecanoic acid	increases expression	1
pentanal	increases expression	1
bisphenol S	affects expression	1
Zoledronic Acid	increases expression	1
Aldehydes	increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Mercuric Chloride	decreases expression	1
Mercury	increases expression	1

Clinical trials (associated diseases)

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