SAA4

Summary

SAA4 (serum amyloid A4, constitutive, HGNC:10516) is a protein-coding gene on chromosome 11p15.1, encoding Serum amyloid A-4 protein (P35542). Major acute phase reactant.

Predicted to be involved in acute-phase response. Located in extracellular exosome.

Source: NCBI Gene 6291 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_006512

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10516
Approved symbol	SAA4
Name	serum amyloid A4, constitutive
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	C-SAA, CSAA
Ensembl gene	ENSG00000148965
Ensembl biotype	protein_coding
OMIM	104752
Entrez	6291

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000278222, ENST00000889031, ENST00000889032, ENST00000889033, ENST00000889034, ENST00000889035, ENST00000889036

RefSeq mRNA: 1 — MANE Select: NM_006512 NM_006512

CCDS: CCDS7832

Canonical transcript exons

ENST00000278222 — 4 exons

Exon	Start	End
ENSE00001307203	18236717	18236802
ENSE00001328165	18231355	18231664
ENSE00003558143	18232395	18232533
ENSE00003660979	18235836	18235930

Expression profiles

Bgee: expression breadth ubiquitous, 113 present calls, max score 99.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.3197 / max 3180.2543, expressed in 14 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118912	4.3197	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.74	gold quality
liver	UBERON:0002107	99.27	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.86	gold quality
minor salivary gland	UBERON:0001830	79.55	gold quality
saliva-secreting gland	UBERON:0001044	79.36	gold quality
thoracic mammary gland	UBERON:0005200	71.23	gold quality
omental fat pad	UBERON:0010414	62.75	gold quality
adenohypophysis	UBERON:0002196	56.39	gold quality
descending thoracic aorta	UBERON:0002345	56.30	gold quality
adipose tissue	UBERON:0001013	55.30	gold quality
tonsil	UBERON:0002372	53.60	gold quality
gastrocnemius	UBERON:0001388	53.38	gold quality
vermiform appendix	UBERON:0001154	52.86	gold quality
gall bladder	UBERON:0002110	52.61	gold quality
left uterine tube	UBERON:0001303	52.12	gold quality
adrenal tissue	UBERON:0018303	51.39	gold quality
right adrenal gland	UBERON:0001233	50.82	gold quality
muscle of leg	UBERON:0001383	50.46	gold quality
right testis	UBERON:0004534	49.95	gold quality
right adrenal gland cortex	UBERON:0035827	49.85	gold quality
left testis	UBERON:0004533	49.78	gold quality
testis	UBERON:0000473	48.90	gold quality
right lung	UBERON:0002167	48.54	gold quality
subcutaneous adipose tissue	UBERON:0002190	48.52	gold quality
skeletal muscle tissue	UBERON:0001134	47.77	gold quality
left adrenal gland	UBERON:0001234	47.73	gold quality
adrenal gland	UBERON:0002369	47.33	gold quality
endocervix	UBERON:0000458	47.23	gold quality
right coronary artery	UBERON:0001625	47.22	gold quality
thoracic aorta	UBERON:0001515	47.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-9	yes	2987.68
E-MTAB-10553	yes	36.17
E-CURD-11	yes	35.09
E-ANND-3	yes	7.42
E-ENAD-17	no	20.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting SAA4, 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-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-339-5P	96.73	66.01	820

Literature-anchored findings (GeneRIF, showing 7)

• The sequences of 1478 and 1836 bp of the SAA1 and SAA4 5’-flanking regions were determined. (PMID:12410800)
• studies provide the first evidence for a novel type of AA amyloidosis in which the fibrils were formed from a mutated SAA4 protein (PMID:20536400)
• Six apolipoproteins (APOA1, APOA2, APOB, APOC2, APOC3, and APOE) were able to differentiate bladder cancer from hernia. SAA4 was significantly increased in bladder cancer subgroups, whereas ProEGF was significantly decreased in bladder cancer subgroups. (PMID:23631828)
• expressed in invasive trophoblast cells (PMID:24951172)
• Data identified SAA4 as a protein that was positively correlated with RF and RA. SAA4 may represent a novel prescreening marker for the diagnosis of RA. (PMID:28505104)
• 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)
• Low SAA4 gene expression is associated with advanced HCC stage and a poor prognosis. (PMID:38300370)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	saa	ENSDARG00000045999
mus_musculus	Saa4	ENSMUSG00000040017
rattus_norvegicus	Saa4	ENSRNOG00000090606
drosophila_melanogaster	CG30467	FBGN0050467

Paralogs (3): SAA2 (ENSG00000134339), SAAL1 (ENSG00000166788), SAA1 (ENSG00000173432)

Protein

Protein identifiers

Serum amyloid A-4 protein — P35542 (reviewed: P35542)

Alternative names: Constitutively expressed serum amyloid A protein

All UniProt accessions (1): P35542

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.

Induction. Constitutively expressed.

Similarity. Belongs to the SAA family.

RefSeq proteins (1): NP_006503* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000096	Serum_amyloid_A	Family
IPR052464	Synovial_Prolif_Regulator	Family

Pfam: PF00277

UniProt features (5 total): signal peptide 1, chain 1, region of interest 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35542-F1	85.45	0.54

Functional residue map

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

Glycosylation sites (1): 94

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 90 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_INFLAMMATORY_RESPONSE, GNF2_GSTM1, GNF2_HPN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, BROWNE_HCMV_INFECTION_48HR_DN, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GNF2_LCAT, HSIAO_LIVER_SPECIFIC_GENES, CAIRO_HEPATOBLASTOMA_DN, GNF2_HPX, MORF_EPHA7, MORF_RAB3A, MORF_WNT1

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

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

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

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAA4	APOA1	P02647	840
SAA4	TTR	P02766	816
SAA4	ACP1	P24666	711
SAA4	CRP	P02741	697
SAA4	LDHC	P07864	697
SAA4	SCIN	Q9Y6U3	653
SAA4	GSN	P06396	628
SAA4	KCNC1	P48547	589
SAA4	APOA2	P02652	574
SAA4	LDHA	P00338	547
SAA4	TLR2	O60603	527
SAA4	CST3	P01034	521
SAA4	APCS	P02743	515
SAA4	HP	P00737	507
SAA4	ORM1	P02763	503

IntAct

11 interactions, top by confidence:

A	B	Type	Score
SAA4	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
SAA4	NUDT9P1	psi-mi:“MI:0915”(physical association)	0.370
IGHG1	PDPK1	psi-mi:“MI:0914”(association)	0.350
UBE2U	IGLL5	psi-mi:“MI:0914”(association)	0.350
KLK10	IGLL5	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
SAA4	CIDEB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): NUDT9P1 (Two-hybrid), SAA4 (Two-hybrid), SAA4 (Affinity Capture-MS), SAA4 (Affinity Capture-MS), SAA4 (Affinity Capture-MS), SAA4 (Cross-Linking-MS (XL-MS)), SAA4 (Cross-Linking-MS (XL-MS)), SAA4 (Cross-Linking-MS (XL-MS)), SAA4 (Cross-Linking-MS (XL-MS)), APOA1 (Cross-Linking-MS (XL-MS)), APOA2 (Cross-Linking-MS (XL-MS)), SAA4 (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

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

461 predictions. Top by Δscore:

Variant	Effect	Δscore
11:18232531:CCC:C	acceptor_gain	1.0000
11:18232532:CCC:C	acceptor_gain	1.0000
11:18231662:CGG:C	acceptor_gain	0.9900
11:18231665:C:CC	acceptor_gain	0.9900
11:18231673:C:CT	acceptor_gain	0.9900
11:18231673:C:T	acceptor_gain	0.9900
11:18232530:ACCC:A	acceptor_gain	0.9900
11:18232531:CCCC:C	acceptor_gain	0.9900
11:18232532:CC:C	acceptor_gain	0.9900
11:18232533:CC:C	acceptor_gain	0.9900
11:18235929:TG:T	acceptor_gain	0.9900
11:18235931:C:CC	acceptor_gain	0.9900
11:18236714:CAC:C	donor_loss	0.9900
11:18236718:TGTGG:T	donor_gain	0.9900
11:18231674:A:T	acceptor_gain	0.9800
11:18235830:TCTTA:T	donor_loss	0.9800
11:18235831:CTTAC:C	donor_loss	0.9800
11:18235832:TTA:T	donor_loss	0.9800
11:18235833:TA:T	donor_loss	0.9800
11:18235834:A:C	donor_loss	0.9800
11:18235835:C:A	donor_loss	0.9800
11:18235891:C:CT	acceptor_gain	0.9800
11:18235892:A:T	acceptor_gain	0.9800
11:18235927:TGTG:T	acceptor_gain	0.9800
11:18231608:CTG:C	acceptor_gain	0.9700
11:18231661:ACGG:A	acceptor_gain	0.9700
11:18231662:CGGC:C	acceptor_gain	0.9700
11:18231663:GG:G	acceptor_gain	0.9700
11:18231664:GCTGC:G	acceptor_gain	0.9700
11:18231666:T:C	acceptor_loss	0.9700

AlphaMissense

853 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:18231532:G:C	F121L	0.922
11:18231532:G:T	F121L	0.922
11:18231534:A:G	F121L	0.922
11:18235855:A:C	F24L	0.902
11:18235855:A:T	F24L	0.902
11:18235857:A:G	F24L	0.902
11:18231557:C:G	R113P	0.856
11:18235899:A:G	C10R	0.853
11:18232408:C:G	A73P	0.838
11:18235836:C:A	G31W	0.836
11:18235904:A:T	V8D	0.824
11:18231562:C:A	W111C	0.822
11:18231562:C:G	W111C	0.822
11:18232458:G:T	A56D	0.818
11:18231560:C:T	G112D	0.814
11:18231533:A:G	F121S	0.809
11:18232438:C:G	A63P	0.803
11:18232441:C:G	A62P	0.801
11:18232410:G:T	A72D	0.795
11:18235845:C:G	A28P	0.794
11:18232455:C:G	R57P	0.792
11:18231564:A:G	W111R	0.782
11:18231564:A:T	W111R	0.782
11:18235836:C:G	G31R	0.782
11:18235836:C:T	G31R	0.782
11:18232429:C:G	G66R	0.775
11:18232429:C:T	G66R	0.775
11:18232448:G:C	N59K	0.775
11:18232448:G:T	N59K	0.775
11:18231561:C:A	G112C	0.767

dbSNP variants (sampled 300 via entrez): RS1000319066 (11:18233676 T>TA), RS1000414249 (11:18236392 T>C,G), RS1000539185 (11:18233914 A>T), RS1001412130 (11:18237942 C>G,T), RS1001728338 (11:18231240 T>A,G), RS1002588700 (11:18232885 T>C), RS1003214119 (11:18235634 A>G), RS1004113026 (11:18232693 G>A), RS1004185017 (11:18232234 G>A), RS1004524458 (11:18236606 C>A,G,T), RS1005014986 (11:18236332 G>A,C), RS1005200754 (11:18233897 C>T), RS1005221746 (11:18232512 G>A,T), RS1007134284 (11:18237352 A>C,G), RS1007368562 (11:18238253 G>A,T)

Disease associations

OMIM: gene MIM:104752 | 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

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, affects methylation, increases expression	6
Aflatoxin B1	affects expression, increases expression	3
Estradiol	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
dicrotophos	decreases expression	1
propionaldehyde	increases expression	1
kojic acid	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
benazol P	affects expression	1
K 7174	decreases expression	1
Zoledronic Acid	increases expression	1
Troglitazone	decreases expression	1
Arbutin	decreases expression	1
Formaldehyde	increases expression	1
Phenobarbital	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression, affects expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Asbestos, Crocidolite	increases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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