SAT1

Summary

SAT1 (spermidine/spermine N1-acetyltransferase 1, HGNC:10540) is a protein-coding gene on chromosome Xp22.11, encoding Diamine acetyltransferase 1 (P21673). Enzyme which catalyzes the acetylation of polyamines.

The protein encoded by this gene belongs to the acetyltransferase family, and is a rate-limiting enzyme in the catabolic pathway of polyamine metabolism. It catalyzes the acetylation of spermidine and spermine, and is involved in the regulation of the intracellular concentration of polyamines and their transport out of cells. Defects in this gene are associated with keratosis follicularis spinulosa decalvans (KFSD). Alternatively spliced transcripts have been found for this gene.

Source: NCBI Gene 6303 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 33 total
• Phenotypes (HPO): 70
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002970

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10540
Approved symbol	SAT1
Name	spermidine/spermine N1-acetyltransferase 1
Location	Xp22.11
Locus type	gene with protein product
Status	Approved
Aliases	SSAT
Ensembl gene	ENSG00000130066
Ensembl biotype	protein_coding
OMIM	313020
Entrez	6303

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 retained_intron, 2 protein_coding, 1 nonsense_mediated_decay

ENST00000379251, ENST00000379253, ENST00000379254, ENST00000379270, ENST00000462639, ENST00000474223, ENST00000487713, ENST00000489394

RefSeq mRNA: 1 — MANE Select: NM_002970 NM_002970

CCDS: CCDS14207

Canonical transcript exons

ENST00000379270 — 6 exons

Exon	Start	End
ENSE00001917283	23785686	23786210
ENSE00001923468	23783173	23783417
ENSE00003554416	23785328	23785429
ENSE00003583791	23785520	23785560
ENSE00003665252	23783800	23783883
ENSE00003677981	23783658	23783709

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 633.7089 / max 28605.9143, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195769	633.7089	1828

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nasal cavity epithelium	UBERON:0005384	99.94	gold quality
epithelium of nasopharynx	UBERON:0001951	99.90	gold quality
monocyte	CL:0000576	99.89	gold quality
nasal cavity mucosa	UBERON:0001826	99.88	gold quality
palpebral conjunctiva	UBERON:0001812	99.87	gold quality
mononuclear cell	CL:0000842	99.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.86	gold quality
amniotic fluid	UBERON:0000173	99.85	gold quality
right lung	UBERON:0002167	99.85	gold quality
leukocyte	CL:0000738	99.83	gold quality
upper lobe of left lung	UBERON:0008952	99.83	gold quality
type B pancreatic cell	CL:0000169	99.82	gold quality
trachea	UBERON:0003126	99.81	gold quality
upper lobe of lung	UBERON:0008948	99.81	gold quality
endothelial cell	CL:0000115	99.79	gold quality
adenohypophysis	UBERON:0002196	99.79	gold quality
epithelium of bronchus	UBERON:0002031	99.78	gold quality
gall bladder	UBERON:0002110	99.78	gold quality
bronchus	UBERON:0002185	99.78	gold quality
periodontal ligament	UBERON:0008266	99.77	gold quality
bronchial epithelial cell	CL:0002328	99.76	gold quality
seminal vesicle	UBERON:0000998	99.76	gold quality
pylorus	UBERON:0001166	99.76	gold quality
left lobe of thyroid gland	UBERON:0001120	99.75	gold quality
spleen	UBERON:0002106	99.75	gold quality
thyroid gland	UBERON:0002046	99.74	gold quality
peritoneum	UBERON:0002358	99.74	gold quality
omental fat pad	UBERON:0010414	99.74	gold quality
pituitary gland	UBERON:0000007	99.73	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.73	gold quality

Single-cell (SCXA)

Detected in 73 experiment(s), a significant marker in 60.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	23132.77
E-GEOD-139324	yes	21622.56
E-MTAB-9435	yes	14113.59
E-MTAB-10885	yes	11685.59
E-MTAB-8495	yes	10849.40
E-CURD-46	yes	10408.27
E-MTAB-9221	yes	9301.24
E-GEOD-149689	yes	9186.39
E-GEOD-130148	yes	9079.15
E-HCAD-15	yes	9079.00
E-CURD-126	yes	7493.85
E-GEOD-81547	yes	6864.59
E-HCAD-13	yes	6485.87
E-HCAD-25	yes	6237.66
E-MTAB-9841	yes	6064.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting SAT1, 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-3064-3P	100.00	70.09	1254
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9-3P	99.96	70.88	2068
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4302	99.89	67.94	1187
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-4670-3P	97.37	68.35	1378
HSA-MIR-624-5P	96.00	68.88	728

Literature-anchored findings (GeneRIF, showing 40)

• Induction of alternatively spliced spermidine/spermine N1-acetyltransferase mRNA in the human kidney cells infected by venezuelan equine encephalitis and tick-borne encephalitis viruses (PMID:12083816)
• overexpression of SSAT and the consequent putrescine accumulation are involved in the keratosis follicularis spinulosa decalvans phenotype (PMID:12215835)
• characterization of promoter function in Hela cells by study of a factor, bound to the responsive element, that underwent modification by binding with another factor after X-ray irradiation (PMID:12427553)
• genomic identification and biochemical characterization of an isoenzyme (PMID:12803540)
• SSAT has a role in apoptosis induced by sulindac sulfone, which leads to reduced tissue polyamine contents in human colon cancer cells (PMID:14506281)
• Transgenic SSAT-overexpressing mice are less active than syngeneic mice and show reduced aggressive behavior; furthermore, SSAT-OE mice have reduced muscle tone and grip strength, although they do not differ from syngeneic mice in several agility tasks. (PMID:15159132)
• SSAT has a role in kidney ischemia-reperfusion injury (PMID:15213272)
• spermidine acetyltransferase directly binds to the alpha9 cytoplasmic domain and mediates alpha9-dependent enhancement of cell migration (PMID:15479742)
• Restoring high inducibility of SSAT activity subverts the reduced sensitivity to cisplatin of SSAT-deficient ovarian cancer cells. (PMID:15905201)
• SSAT and SMO(PAOh1) activities are the major mediators of the cellular response of breast tumor cells to polyamines while PAO plays little or no role in this response (PMID:16207710)
• Activation of SSAT by aspirin and different NSAIDs may be a common property of NSAIDs that plays an important role in their chemopreventive actions in colorectal cancer. (PMID:16262603)
• tertiary structure of hSSAT reported in this article provides a sound basis for the in-depth study of its structure-function relationship (PMID:16544326)
• The inhibition of IkappaB and activation of NFkappaB activate SSAT. (PMID:16637064)
• a common mediator of inflammation can lead to the induction of SSAT expression by activating the NFkappaB signaling pathway in non-small cell lung cancer cells (PMID:16757480)
• Pharmacological activation of PPARgamma and/or induction of SSAT may represent a therapeutic or preventive strategy for treating colorectal cancer. (PMID:16854216)
• These results indicate that the disruption of polyamine homeostasis due to enhanced SSAT activity leads to DNA damage and reduced cell proliferation via activation of DNA repair and cell cycle checkpoint and disruption of Raf –> MEK –> ERK pathways. (PMID:17065202)
• The structure of the SSAT-spermine-acetyl-coenzyme A complex suggested that Tyr140 acts as general acid and Glu92, through one or more water molecules, acts as the general base during catalysis. (PMID:17516632)
• SSAT1, which shares 46% amino acid identity with SSAT2, also binds to HIF-1alpha and promotes its ubiquitination/degradation. However, in contrast to SSAT2, SSAT1 acts by stabilizing the interaction of HIF-1alpha with RACK1 (PMID:17875644)
• Adenovirus-mediated expression of SSAT inhibits colorectal cancer cell growth in vitro. (PMID:18430370)
• interaction between SLC3A2 and SAT1 suggests that these proteins may facilitate excretion of acetylated polyamines. (PMID:18660501)
• This is the first study linking polymorphic variants of genes involved in polyamine metabolism with anxiety disorders. (PMID:18759322)
• Our study provides new results which show that dysregulation of SSAT expression does play a role in suicide behavior. (PMID:19051286)
• Downregulation of SAT1 expression may play a role in depression and suicidality. (PMID:19152344)
• We failed to demonstrate a significant association between the SAT-1 single nucleotide polymorphism and schizophrenia (PMID:19162121)
• results indicate that specific promoter variants in SAT1 have an effect on SAT1 gene expression. (PMID:19446796)
• Adenovirus vector-mediated upregulation of spermidine /spermine N1-acetyltransferase impairs human gastric cancer growth in vitro and in vivo. (PMID:19686286)
• Knockdown studies suggest that induction of SSAT and SMO is correlated with the antiproliferative effects of BENSpm with 5-FU or paclitaxel in MDA-MB-231 cells. (PMID:19727732)
• These results add support for a role of SAT1 in conferring a risk for suicide completion, in particular in the context of depressive disorders. (PMID:19851986)
• SSAT1 may regulate exogenous gene expression by blocking steps involved in transcription/translation from an episomal vector by targeting non-polyamine substrate(s) critical for this pathway (PMID:20212040)
• Studies indicate that each of the 4 genes was associated with at least one main outcome: anxiety (SAT1, SMS), mood disorders (SAT1, SMOX), and suicide attempts (SAT1, OATL1). (PMID:21152090)
• The results of this study indicated that epigenetic factors in the promoter region of SAT1 influence gene expression levels, and may provide a mechanism for both our previous findings of haplotype-specific effects of promoter variations on SAT1 expression (PMID:21501848)
• SSAT induction plays a role in cell detachment and apoptosis of glioblastoma cells by N1,N11-diethylnorspermine treatment. (PMID:22179681)
• SSAT translational control mechanisms (PMID:22354986)
• SAT1 transcription is influenced by lithium and this effect is altered in bipolar disease patients who completed suicide. (PMID:23768751)
• EBV-positive Akata cells demonstrated decreased SAT1 enzyme activity concomitant with altered intracellular polyamine level. (PMID:23891576)
• berberine inhibits cellular growth by affecting polyamine metabolism, in particular through the upregulation of the key catabolic enzyme, spermidine/spermine N1-acetyltransferase (SSAT). (PMID:23903781)
• The Catabolic enzyme SSAT expression levels was up-regulated in both cell lines; however, the specific SSAT siRNA treatments prevented the EBR-induced apoptosis only in LNCaP (AR+) cells. (PMID:23963538)
• study postulates a mechanism for SAT1 and SMOX down-regulation by post-transcriptional activity of miRNAs. (PMID:24025154)
• In females, the TC genotype was significantly more frequent in alcohol-dependent patients than in non-alcohol-dependent psychiatric controls. No differences were found among the males. (PMID:24735382)
• A role for SAT1 in homologous recombination. (PMID:25277523)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	sat1b	ENSDARG00000032272
danio_rerio	sat1a.1	ENSDARG00000035652
danio_rerio	SAT1	ENSDARG00000095908
mus_musculus	Sat1	ENSMUSG00000025283
rattus_norvegicus	Sat1	ENSRNOG00000003809
drosophila_melanogaster	CG4210	FBGN0038302
caenorhabditis_elegans		WBGENE00008408

Paralogs (2): SAT2 (ENSG00000141504), SATL1 (ENSG00000184788)

Protein

Protein identifiers

Diamine acetyltransferase 1 — P21673 (reviewed: P21673)

Alternative names: Polyamine N-acetyltransferase 1, Putrescine acetyltransferase, Spermidine/spermine N(1)-acetyltransferase 1

All UniProt accessions (4): P21673, A0A384NQ10, E9PD37, Q2TM25

UniProt curated annotations — full annotation on UniProt →

Function. Enzyme which catalyzes the acetylation of polyamines. Substrate specificity: norspermidine = spermidine » spermine > N(1)-acetylspermine. This highly regulated enzyme allows a fine attenuation of the intracellular concentration of polyamines. Also involved in the regulation of polyamine transport out of cells. Also acts on 1,3-diaminopropane and 1,5-diaminopentane.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cytosol.

Disease relevance. Overexpression of SAT1 and the consequent putrescine accumulation might play a role in the pathogenesis of keratosis follicularis spinulosa decalvans.

Pathway. Amine and polyamine degradation; putrescine degradation; N-acetylputrescine from putrescine: step 1/1.

Similarity. Belongs to the acetyltransferase family.

RefSeq proteins (1): NP_002961* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000182	GNAT_dom	Domain
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily
IPR051016	Diverse_Substrate_AcTransf	Family

Pfam: PF00583

Enzyme classification (BRENDA):

• EC 2.3.1.57 — diamine N-acetyltransferase (BRENDA: 27 organisms, 270 substrates, 52 inhibitors, 104 Km, 34 kcat entries)

Substrate kinetics (BRENDA)

26 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SPERMIDINE	0.022–4	25
SPERMINE	0.0037–1.7	25
ACETYL-COA	0.0015–0.35	11
1,3-DIAMINOPROPANE	0.107–20.6	5
PUTRESCINE	0.25–25.3	5
SYM-NORSPERMIDINE	0.008–0.5	3
1,5-DIAMINOPENTANE	0.1–0.44	2
L-LYSINE	6.1–8	2
L-ORNITHINE	2.4–2.6	2
MALONYL-COA	0.186–0.264	2
N1-ACETYLSPERMINE	0.03–0.295	2
1,12-DIAMINO-3,6,9-TRIAZADODECANE	0.106	1
1,6-DIAMINOHEXANE	0.4	1
1,7-DIAMINOHEPTANE	1.59	1
15-DEOXYSPERGUALIN	0.012	1

Catalyzed reactions (Rhea), 3 shown:

• an alkane-alpha,omega-diamine + acetyl-CoA = an N-acetylalkane-alpha,omega-diamine + CoA + H(+) (RHEA:11116)
• spermidine + acetyl-CoA = N(1)-acetylspermidine + CoA + H(+) (RHEA:28150)
• spermine + acetyl-CoA = N(1)-acetylspermine + CoA + H(+) (RHEA:33099)

UniProt features (36 total): helix 10, strand 9, binding site 8, sequence conflict 3, turn 2, chain 1, domain 1, mutagenesis site 1, active site 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
2B5G	X-RAY DIFFRACTION	1.7
2G3T	X-RAY DIFFRACTION	1.8
2B3U	X-RAY DIFFRACTION	1.85
2B3V	X-RAY DIFFRACTION	1.95
2B58	X-RAY DIFFRACTION	1.95
2B4B	X-RAY DIFFRACTION	2
2B4D	X-RAY DIFFRACTION	2
2FXF	X-RAY DIFFRACTION	2
2F5I	X-RAY DIFFRACTION	2.3
2JEV	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21673-F1	96.63	0.96

Functional residue map

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

Catalytic / active sites (1): 140 (proton donor)

Ligand- & substrate-binding residues (8): 152; 27–28; 92; 94–96; 102–107; 126–128; 133–136; 140–143

Mutagenesis-validated functional residues (1):

Position	Phenotype
140	reduces activity by 95%.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-351200	Interconversion of polyamines
R-HSA-1430728	Metabolism
R-HSA-351202	Metabolism of polyamines
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 576 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, RRAGTTGT_UNKNOWN, DAVIES_MULTIPLE_MYELOMA_VS_MGUS_DN, LEE_NEURAL_CREST_STEM_CELL_DN, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, MCLACHLAN_DENTAL_CARIES_UP, XU_HGF_TARGETS_REPRESSED_BY_AKT1_UP, HARRIS_HYPOXIA, BASSO_B_LYMPHOCYTE_NETWORK, SHEPARD_CRASH_AND_BURN_MUTANT_UP, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOZGIT_ESR1_TARGETS_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP

GO Biological Process (5): angiogenesis (GO:0001525), polyamine biosynthetic process (GO:0006596), putrescine catabolic process (GO:0009447), obsolete spermidine acetylation (GO:0032918), regulation of cell population proliferation (GO:0042127)

GO Molecular Function (8): diamine N-acetyltransferase activity (GO:0004145), N-acetyltransferase activity (GO:0008080), spermidine binding (GO:0019809), identical protein binding (GO:0042802), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of polyamines	1
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
polyamine metabolic process	1
biogenic amine biosynthetic process	1
polyamine catabolic process	1
putrescine metabolic process	1
cell population proliferation	1
regulation of cellular process	1
N-acetyltransferase activity	1
acetyltransferase activity	1
polyamine binding	1
cation binding	1
protein binding	1
binding	1
catalytic activity	1
transferase activity	1
acyltransferase activity	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1192 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAT1	PAOX	Q6QHF9	987
SAT1	PMF1	Q6P1K2	909
SAT1	A0A087WT04	A0A087WT04	907
SAT1	ODC1	P11926	856
SAT1	SMOX	Q9NWM0	853
SAT1	NFE2L2	Q16236	814
SAT1	GLYATL1	Q969I3	806
SAT1	SMS	P52788	782
SAT1	SRM	P19623	741
SAT1	ITGA9	Q13797	722
SAT1	ELOC	Q15369	705
SAT1	GCLM	P48507	692
SAT1	KEAP1	Q14145	643
SAT1	NSL1	Q96IY1	604
SAT1	LPCAT3	Q6P1A2	593

IntAct

246 interactions, top by confidence:

A	B	Type	Score
SAT1	TCF25	psi-mi:“MI:0915”(physical association)	0.910
TCF25	SAT1	psi-mi:“MI:0915”(physical association)	0.910
SAT1	RBM17	psi-mi:“MI:0915”(physical association)	0.870
RBM17	SAT1	psi-mi:“MI:0915”(physical association)	0.870
LNX1	SAT1	psi-mi:“MI:0915”(physical association)	0.830
SAT1	LNX1	psi-mi:“MI:0915”(physical association)	0.830
SAT1	SAT2	psi-mi:“MI:0915”(physical association)	0.800
HOXB9	SAT1	psi-mi:“MI:0915”(physical association)	0.760
SAT1	HOXB9	psi-mi:“MI:0915”(physical association)	0.760
SAT1	SAT1	psi-mi:“MI:0915”(physical association)	0.740
SAT1	SAT1	psi-mi:“MI:0407”(direct interaction)	0.740
SAT1	CASP7	psi-mi:“MI:0915”(physical association)	0.720
SAT1	DIPK1B	psi-mi:“MI:0915”(physical association)	0.720
CCHCR1	SAT1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (124): SAT1 (Two-hybrid), SAT1 (Two-hybrid), SAT1 (Two-hybrid), SAT1 (Two-hybrid), SNAI2 (Two-hybrid), EIF3D (Two-hybrid), MTA1 (Two-hybrid), DDX39A (Two-hybrid), TCF25 (Two-hybrid), FAM156A (Two-hybrid), CCHCR1 (Two-hybrid), DMRT3 (Two-hybrid), LNX1 (Two-hybrid), RBM17 (Two-hybrid), CCDC148 (Two-hybrid)

ESM2 similar proteins: A0A0C5DM37, A0A2I7G3B3, A0A7H0DN16, A6ZW78, B3LKQ3, B5VSZ6, E3Q1H1, O13738, O13748, O17731, O42881, O43976, O74311, O74457, O93806, O94048, P06242, P21673, P28475, P32363, P36973, P43577, P48026, P49431, P79081, Q01612, Q03503, Q06592, Q07523, Q10081, Q17427, Q1PCB1, Q21012, Q28999, Q3T0Q0, Q3ZBW2, Q54MP9, Q54RF5, Q54WR8, Q5U1Y4

Diamond homologs: D4FZ53, P21673, P39909, P48026, P49431, Q28999, Q3T0Q0, Q9JHW6, Q01612, Q6P8J2, Q7PCJ8, Q7PCJ9, Q86VE3, Q8AXL1, Q96F10, Q9D5N8, Q9ZV05, E3Q1H1, O17731, P08457, P79081, Q58604, O05517, O29729, P63423, P63424, Q57LQ8, Q5PI26, P43577, Q2NS89, Q9ZV06, Q44245

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CSNK2A1	unknown	SAT1	phosphorylation
CSNK2A2	unknown	SAT1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

664 predictions. Top by Δscore:

Variant	Effect	Δscore
X:23783413:TCAAG:T	donor_loss	1.0000
X:23783415:AAG:A	donor_loss	1.0000
X:23783417:GGT:G	donor_loss	1.0000
X:23783418:G:GA	donor_loss	1.0000
X:23783642:A:AG	acceptor_gain	1.0000
X:23783642:AT:A	acceptor_gain	1.0000
X:23783642:ATGT:A	acceptor_gain	1.0000
X:23783643:T:G	acceptor_gain	1.0000
X:23783643:T:TA	acceptor_gain	1.0000
X:23783645:T:TA	acceptor_gain	1.0000
X:23783648:A:AG	acceptor_gain	1.0000
X:23783649:T:G	acceptor_gain	1.0000
X:23783710:GT:G	donor_loss	1.0000
X:23783881:A:T	donor_gain	1.0000
X:23785325:CA:C	acceptor_loss	1.0000
X:23785326:A:AG	acceptor_gain	1.0000
X:23785327:G:GG	acceptor_gain	1.0000
X:23785425:TAGAG:T	donor_loss	1.0000
X:23785426:AGAG:A	donor_loss	1.0000
X:23785427:GAGG:G	donor_loss	1.0000
X:23785428:AGGT:A	donor_loss	1.0000
X:23785429:GGT:G	donor_loss	1.0000
X:23785430:G:T	donor_loss	1.0000
X:23785431:T:G	donor_loss	1.0000
X:23785515:TTTA:T	acceptor_loss	1.0000
X:23785516:TTA:T	acceptor_loss	1.0000
X:23785518:A:AG	acceptor_gain	1.0000
X:23785518:AG:A	acceptor_gain	1.0000
X:23785519:G:GG	acceptor_gain	1.0000
X:23785519:GG:G	acceptor_gain	1.0000

AlphaMissense

1140 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:23783803:T:C	L41P	0.998
X:23785343:G:A	G73D	0.998
X:23785382:G:A	G86D	0.998
X:23785382:G:T	G86V	0.998
X:23783817:T:C	F46L	0.997
X:23783819:T:A	F46L	0.997
X:23783819:T:G	F46L	0.997
X:23783841:T:C	C54R	0.997
X:23783848:T:A	V56D	0.997
X:23785349:C:A	A75D	0.997
X:23783410:T:C	L20P	0.996
X:23783815:G:A	G45D	0.996
X:23783843:C:G	C54W	0.996
X:23785342:G:C	G73R	0.996
X:23785397:T:A	L91H	0.996
X:23785397:T:C	L91P	0.996
X:23785412:T:A	V96E	0.996
X:23785532:G:A	G106E	0.996
X:23785706:C:G	C122W	0.996
X:23785720:T:C	F127S	0.996
X:23783662:T:C	L24P	0.995
X:23783665:C:A	A25D	0.995
X:23785400:A:T	E92V	0.995
X:23785544:T:C	L110P	0.995
X:23785747:C:T	S136F	0.995
X:23785774:C:A	A145D	0.995
X:23783377:C:A	A9D	0.994
X:23783814:G:C	G45R	0.994
X:23783835:T:G	Y52D	0.994
X:23783851:C:A	A57E	0.994

dbSNP variants (sampled 300 via entrez): RS1000395190 (X:23785410 C>T), RS1000485695 (X:23782898 CA>C), RS1000750683 (X:23782967 G>A), RS1000819716 (X:23785029 G>A,C), RS1001586226 (X:23784458 T>C), RS1001902100 (X:23782784 T>G), RS1002825748 (X:23783275 C>A,T), RS1004816993 (X:23784165 G>A,C), RS1005254003 (X:23781901 A>C), RS1005614739 (X:23782264 A>G), RS1005836274 (X:23786384 T>C,G), RS1006064449 (X:23783736 A>G), RS1007758943 (X:23781404 C>G,T), RS1008588556 (X:23786110 A>G), RS1009230412 (X:23781302 G>A,T)

Disease associations

OMIM: gene MIM:313020 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
systemic lupus erythematosus	Strong	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
pediatric systemic lupus erythematosus	Limited	XL

Mondo (1): systemic lupus erythematosus (MONDO:0007915)

Orphanet (0):

HPO phenotypes

70 total (30 of 70 shown, HPO-id order):

HPO	Term
HP:0000079	Abnormality of the urinary system
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000100	Nephrotic syndrome
HP:0000123	Nephritis
HP:0000155	Oral ulcer
HP:0000498	Blepharitis
HP:0000509	Conjunctivitis
HP:0000613	Photophobia
HP:0000653	Sparse eyelashes
HP:0000707	Abnormality of the nervous system
HP:0000709	Psychosis
HP:0000790	Hematuria
HP:0000951	Abnormality of the skin
HP:0000969	Edema
HP:0000982	Palmoplantar keratoderma
HP:0000988	Skin rash
HP:0000989	Pruritus
HP:0001041	Facial erythema
HP:0001047	Atopic dermatitis
HP:0001131	Corneal dystrophy
HP:0001250	Seizure
HP:0001324	Muscle weakness
HP:0001369	Arthritis
HP:0001541	Ascites
HP:0001596	Alopecia
HP:0001698	Pericardial effusion
HP:0001873	Thrombocytopenia
HP:0001882	Decreased total leukocyte count
HP:0001888	Decreased total lymphocyte count

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4286 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 29,042 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL55	PENTAMIDINE	4	27,049
CHEMBL35241	DIMINAZENE	2	1,993

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 5 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.70	Ki	2000	nM	PENTAMIDINE
5.62	Ki	2400	nM	DIMINAZENE

PubChem BioAssay actives

2 with measured affinity, of 61 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Pentamidine	1124816: Inhibition of human SSAT using spermidine as substrate	ki	2.0000	uM
4-[2-(4-carbamimidoylphenyl)iminohydrazinyl]benzenecarboximidamide	1124816: Inhibition of human SSAT using spermidine as substrate	ki	2.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects cotreatment, affects expression, decreases expression, increases expression, increases methylation	8
(+)-JQ1 compound	increases expression	6
Fluorouracil	affects cotreatment, increases expression, increases activity, decreases response to substance, affects reaction	6
Tretinoin	affects cotreatment, increases expression	6
Valproic Acid	affects cotreatment, increases expression	6
trichostatin A	affects cotreatment, increases expression, affects expression	5
N(1),N(11)-diethylnorspermine	decreases reaction, increases activity, affects reaction, affects binding, affects cotreatment (+2 more)	4
Cisplatin	affects expression, increases expression, affects cotreatment	4
Estradiol	decreases expression	4
bisphenol A	increases expression, affects expression, decreases expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
belinostat	affects cotreatment, increases expression	3
Oxaliplatin	affects cotreatment, increases expression	3
Acetaminophen	affects expression, increases expression	3
Doxorubicin	decreases expression, increases expression, decreases response to substance	3
Tobacco Smoke Pollution	increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	3
Cyclosporine	increases expression, decreases expression	3
sulindac sulfone	increases expression, increases reaction, affects binding, increases activity	2
didecyldimethylammonium	increases expression	2
nickel sulfate	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
perfluorooctane sulfonic acid	increases expression, decreases expression	2
Temozolomide	affects response to substance, increases expression	2
Decitabine	affects expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Carbamazepine	affects expression	2
Copper	decreases expression, increases expression, affects binding	2

ChEMBL screening assays

22 unique, capped per target: 12 admet, 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2185110	Binding	Activity of SSAT in human DU145 cells assessed per ug DNA at 100 uM after 72 hrs in presence of serum amine oxidase inhibitor aminoguanidine (RVb = 62 +/- 4 pmol/h per ug DNA)	The use of novel C-methylated spermidine derivatives to investigate the regulation of polyamine metabolism. — J Med Chem
CHEMBL3538524	ADMET	Drug level in human HepG2 cells assessed as SSAT1-mediated compound formation treated with SpmTrien at 100 uM for 24 hrs pretreated with 50 uM DENSpm for 24 hrs	Metabolism of triethylenetetramine and 1,12-diamino-3,6,9-triazadodecane by the spermidine/spermine-N(1)-acetyltransferase and thialysine acetyltransferase. — Drug Metab Dispos

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_VD88	H157R	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00120887	PHASE4	COMPLETED	Lupus Atherosclerosis Prevention Study
NCT00125307	PHASE4	COMPLETED	Tacrolimus for the Treatment of Systemic Lupus Erythematosus With Membranous Nephritis
NCT00188188	PHASE4	UNKNOWN	Study of Endothelial Dysfunction in Systemic Lupus and Its Role in Heart Disease
NCT00371501	PHASE4	COMPLETED	Aspirin and Statins for Prevention of Atherosclerosis and Arterial Thromboembolism in Systemic Lupus Erythematosus
NCT00392093	PHASE4	COMPLETED	Effect of Hormone Replacement Therapy on Lupus Activity
NCT00413361	PHASE4	COMPLETED	The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
NCT00508898	PHASE4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00668330	PHASE4	COMPLETED	Steroid Induced Osteoporosis in Patients With Systemic Lupus Erythematosus
NCT00739050	PHASE4	TERMINATED	Effect of Simvastatin on Endothelial Function in Premenopausal Women With Systemic Lupus Erythematosus (0733-271)(TERMINATED)
NCT00815282	PHASE4	COMPLETED	Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
NCT00828178	PHASE4	COMPLETED	Efficacy of Fish Oil in Lupus Patients
NCT00866229	PHASE4	UNKNOWN	Efficacy and Adverse Effect of Simvastatin Compare to Rosuvastatin in Systemic Lupus Erythematosus (SLE) Patients With Corticosteroid Therapy and High Low-Density Lipoprotein (LDL) Cholesterol Level
NCT00911521	PHASE4	COMPLETED	Immunogenicity and Safety of a Quadrivalent Human Papillomavirus (HPV) Vaccine in Patients With SLE: a Controlled Study
NCT01101802	PHASE4	COMPLETED	Mycophenolate Mofetil in Systemic Lupus Erythematosus (MISSILE)
NCT01112215	PHASE4	COMPLETED	Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01276782	PHASE4	WITHDRAWN	Levothyroxine in Pregnant SLE Patients
NCT01322308	PHASE4	COMPLETED	Effect of Pioglitazone on Endothelial Function in Premenopausal Women With Uncomplicated Systemic Lupus Erythematosus
NCT01359826	PHASE4	WITHDRAWN	The Effect of Milnacipran on Fatigue and Quality of Life in Lupus Patients
NCT01597492	PHASE4	COMPLETED	A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)
NCT01632241	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
NCT01705977	PHASE4	COMPLETED	Belimumab Assessment of Safety in SLE
NCT01753401	PHASE4	COMPLETED	Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
NCT02270970	PHASE4	UNKNOWN	Evaluation of Belimumab Impact on a BLyS Activity Signature Test in the Absence of Confounding Polypharmacy
NCT02477150	PHASE4	COMPLETED	Safety and Immunogenicity of a Zoster Vaccine in SLE
NCT02741960	PHASE4	COMPLETED	The Effect of Metformin on Reducing Lupus Flares
NCT02779153	PHASE4	WITHDRAWN	Acthar SLE (Systemic Lupus Erythematosus)
NCT02953821	PHASE4	COMPLETED	Acthar Gel for Active Systemic Lupus Erythematosus (SLE)
NCT03042260	PHASE4	UNKNOWN	Prophylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous
NCT03098823	PHASE4	COMPLETED	A Crossover Study to Compare RAYOS to IR Prednisone to Improve Fatigue and Morning Symptoms for SLE
NCT03122431	PHASE4	COMPLETED	Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases
NCT03543839	PHASE4	RECRUITING	Trial of Belimumab in Early Lupus
NCT04447053	PHASE4	UNKNOWN	Sequential Belimumab and T-cell Based Therapy in SLE
NCT04515719	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in SLE Patients
NCT04893161	PHASE4	UNKNOWN	A Model About the Response of Belimumab in SLE
NCT04908865	PHASE4	COMPLETED	Open-label Study of Belimumab Plus Standard Therapy in Chinese Pediatric Participants With Active Systemic Lupus Erythematosus (SLE)
NCT04956484	PHASE4	COMPLETED	Belimumab In Early Systemic Lupus Erythematosus
NCT05559671	PHASE4	RECRUITING	Safety of the Herpes Zoster Subunit Vaccine in Lupus
NCT05666336	PHASE4	UNKNOWN	Multi-omics Studies on the Efficacy of Telitacicept in Chinese SLE Patients
NCT05748925	PHASE4	COMPLETED	Cardio Renal Effects of SGLT2 Inhibitors Among Lupus Nephritis Patients