SAT1

Chr X

spermidine/spermine N1-acetyltransferase 1

Also known as: DC21, KFSD, KFSDX, SAT, SSAT, SSAT-1

NCBI Gene: 6303ENSG00000130066UniProt: Q9H2B4

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.[provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

UniProtNephrolithiasis, calcium oxalate, 1
UniProtHypersulfaturia
68
ClinVar variants
55
Pathogenic / LP
0.87
pLI score
2
Active trials
Clinical Summary— SAT1
🧬
Gene-Disease Validity (ClinGen)
pediatric systemic lupus erythematosus · XLLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
55 Pathogenic / Likely Pathogenic· 9 VUS of 68 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.45LOEUF
pLI 0.871
Z-score 2.40
OE 0.00 (0.00–0.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.71Z-score
OE missense 0.40 (0.29–0.55)
25 obs / 63.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.40 (0.29–0.55)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.57
0≤1.21.6
LoF obs/exp: 0 / 6.7Missense obs/exp: 25 / 63.1Syn Z: -2.17

ClinVar Variant Classifications

68 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic55
VUS9
Likely Benign2
Benign1
Conflicting1
55
Pathogenic
9
VUS
2
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————55
Likely Pathogenic
————0
VUS
————9
Likely Benign
————2
Benign
————1
Conflicting
—1
Total—68

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SAT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The polyamine-regulating enzyme SSAT1 impairs tissue regulatory T cell function in chronic cutaneous inflammation.
Neuwirth T et al.·Immunity
2025
Loss-of-function variants in SAT1 cause X-linked childhood-onset systemic lupus erythematosus.
Xu L et al.·Ann Rheum Dis
2022
MNT inhibits lung adenocarcinoma ferroptosis and chemosensitivity by suppressing SAT1.
Zhao G et al.·Commun Biol
2024
SLC26A1 is a major determinant of sulfate homeostasis in humans.
Pfau A et al.·J Clin Invest
2023
Identification of ferroptosis-related genes associated with diffuse large B-cell lymphoma via bioinformatics and machine learning approaches.
Jia Z et al.·Int J Biol Macromol
2024
Sea buckthorn extract mitigates chronic obstructive pulmonary disease by suppression of ferroptosis via scavenging ROS and blocking p53/MAPK pathways.
Liu L et al.·J Ethnopharmacol
2025
The sat1 Gene Is Required for the Growth and Virulence of the Human Pathogenic Fungus Aspergillus fumigatus.
Wei Y et al.·Microbiol Spectr
2022
Polyamine Catabolism in Acute Kidney Injury.
Zahedi K et al.·Int J Mol Sci
2019Review
Whole-gene sequencing investigation of SAT1 in attempted suicide.
Monson ET et al.·Am J Med Genet B Neuropsychiatr Genet
2016
Polyamine acetylation mediates crosstalk between cancer cells and myeloid cells to promote mesenchymal/plurimetabolic states in glioblastoma.
Rana AB et al.·Neuro Oncol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Current situation and emerging foot-and-mouth disease virus lineages in Egypt: Historicment SAT1 Introduction, and Vaccine Policy Implications.
Abousenna MS.·Vet Immunol Immunopathol
2026
HERVH-derived eRNA activates a super-enhancer-driven ALDH1A3/SAT1 axis to promote ferroptosis escape and pancreatic cancer development.
Yuan L et al.·Sci Adv
2025🔓 Open Access
Ferroptosis-Related Gene SAT1 Contributes to Immune Responses in Acute Pancreatitis.
Zhou K et al.·J Gene Med
2025
Alcoholic extract of Salvia castanea Diels f. tomentosa Stib. ameliorates hypobaric hypoxia-induced right ventricular hypertrophy by inhibiting the P53-SAT1-ALOX15 pathway and up-regulating the SLC7A11-GPX4 pathway.
Wu J et al.·J Nat Med
2026
Schwann Cell-Derived Extracellular Vesicles MFG-E8 Alleviates Neuropathic Pain After Peripheral Nerve Injury Through Inhibiting Ferroptosis in Dorsal Root Ganglion Neurons by Regulating the PPARγ/p53/SAT1/ALOX15 Pathway.
Cao J et al.·J Neurochem
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Single Cell Sequencing TechnologyGene Expression ProfilingGene Expression

Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA. a Prospective Study Will Evaluate the Performance of Direct LS-TA in Triage Febrile Patients Into Major Categories of Infections: Viral, Bacterial or Active Tuberculosis.

NOT YET RECRUITING
NCT06846645Chinese University of Hong KongStarted 2025-02
No intervention
Gene ExpressionGene Expression ProfilingInfection

Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA

ACTIVE NOT RECRUITING
NCT06838780Chinese University of Hong KongStarted 2018-01-01
No intervention

External Resources

Links to major genomics databases and tools