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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
RPSA
ribosomal protein SA
Chromosome 3 Β· 3p22.1
NCBI Gene: 3921Ensembl: ENSG00000168028.15HGNC: HGNC:6502UniProt: A0A0C4DG17
384PubMed Papers
21Diseases
6Drugs
9Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneReceptor
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
DNA bindingRNA bindingstructural constituent of ribosomeribosome bindingfamilial isolated congenital aspleniainfluenzaDuchenne muscular dystrophycystic fibrosis
✦AI Summary

RPSA (ribosomal protein SA) is a multifunctional protein with dual roles as a structural component of the small ribosomal subunit and an extracellular receptor. Primarily, RPSA is essential for ribosome biogenesis, as mutations in this gene cause approximately half of all isolated congenital asplenia cases through impaired pre-rRNA processing and disruption of spleen patterning genes 1. Beyond its ribosomal function, RPSA translocates to the cell surface where it acts as a receptor for bacterial pathogens, including Streptococcus suis serotype 2, which exploits RPSA-mediated biomolecular condensation to induce host cell apoptosis 2. RPSA also participates in neuromorphogenesis through PEDF-RPSA-Itga6 signaling, regulating dendritic morphology and cortical development 3. Disease relevance extends to neurodegenerative conditions: RPSA expression is significantly upregulated in Alzheimer's disease brain capillaries alongside elevated protein processing machinery 4, and genome-wide analyses identify RPSA-MOBP loci variants as genetic risk factors for sporadic frontotemporal dementia 5. Clinically, RPSA inhibition shows promise in genetic Alzheimer's disease by modulating endosomal trafficking and reducing amyloidogenic APP processing 6. RPSA's interaction with the cellular prion protein influences tumorigenesis through effects on cell growth, migration, and invasion 7, suggesting broader oncological relevance.

Sources cited
1
RPSA mutations underlie approximately half of isolated congenital asplenia cases; RPSA is required for pre-rRNA processing and spleen patterning gene expression
PMID: 30337486
2
RPSA translocates from cytosol to cell surface as a bacterial receptor; pathogenic enolase promotes RPSA biomolecular condensation and host cell apoptosis
PMID: 38331785
3
RPSA regulates cortical neuronal morphogenesis via PEDF ligand and Itga6 interaction; Rpsa deficiency causes apical dendrite defects and reduced spine density
PMID: 34347028
4
RPSA is significantly upregulated in Alzheimer's disease brain capillaries, correlating with increased protein processing and N-glycosylation machinery
PMID: 35766008
5
RPSA-MOBP loci variants are associated with increased risk for sporadic frontotemporal dementia through effects on brain cortex gene expression
PMID: 38889728
6
RPSA inhibition reduces APP accumulation in endosomes and decreases amyloidogenic APP processing and AΞ² production in Alzheimer's disease fibroblasts
PMID: 40037473
7
RPSA interacts with cellular prion protein and modulates tumorigenesis through effects on cell growth, migration, invasion, and cell death
PMID: 37452879
Disease Associationsβ“˜21
familial isolated congenital aspleniaOpen Targets
0.76Strong
influenzaOpen Targets
0.47Moderate
Duchenne muscular dystrophyOpen Targets
0.46Moderate
cystic fibrosisOpen Targets
0.39Weak
COVID-19Open Targets
0.37Weak
dengue diseaseOpen Targets
0.37Weak
severe acute respiratory syndromeOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.14Weak
neoplasmOpen Targets
0.12Weak
Becker muscular dystrophyOpen Targets
0.10Weak
infectionOpen Targets
0.10Weak
cancerOpen Targets
0.10Suggestive
non-Hodgkins lymphomaOpen Targets
0.10Suggestive
aniridiaOpen Targets
0.10Suggestive
rheumatoid arthritisOpen Targets
0.09Suggestive
genetic disorderOpen Targets
0.09Suggestive
hypertrophic cardiomyopathyOpen Targets
0.08Suggestive
hepatitis B virus infectionOpen Targets
0.08Suggestive
small cell lung carcinomaOpen Targets
0.08Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.08Suggestive
Asplenia, isolated congenitalUniProt
Pathogenic Variants9
NM_002295.6(RPSA):c.659_663del (p.Lys220fs)Likely pathogenic
Familial isolated congenital asplenia
β˜…β˜†β˜†β˜†2025β†’ Residue 220
NM_002295.6(RPSA):c.493A>T (p.Asn165Tyr)Likely pathogenic
Familial isolated congenital asplenia
β˜…β˜†β˜†β˜†2024β†’ Residue 165
NM_002295.6(RPSA):c.538C>T (p.Arg180Trp)Pathogenic
Familial isolated congenital asplenia|not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 180
NM_002295.6(RPSA):c.556C>T (p.Arg186Cys)Likely pathogenic
Familial isolated congenital asplenia|not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 186
NM_002295.6(RPSA):c.161C>A (p.Thr54Asn)Pathogenic
Familial isolated congenital asplenia
β˜†β˜†β˜†β˜†2013β†’ Residue 54
NM_002295.6(RPSA):c.172C>T (p.Leu58Phe)Pathogenic
Familial isolated congenital asplenia
β˜†β˜†β˜†β˜†2013β†’ Residue 58
NM_002295.6(RPSA):c.25C>T (p.Gln9Ter)Pathogenic
Familial isolated congenital asplenia
β˜†β˜†β˜†β˜†2013β†’ Residue 9
NM_002295.6(RPSA):c.590_594dup (p.Pro199fs)Pathogenic
Familial isolated congenital asplenia
β˜†β˜†β˜†β˜†2013β†’ Residue 199
NM_002295.6(RPSA):c.538C>G (p.Arg180Gly)Pathogenic
Familial isolated congenital asplenia
β˜†β˜†β˜†β˜†2013β†’ Residue 180
View on ClinVar β†—
Drug Targets6
ATALURENApproved
80S Ribosome modulator
Duchenne muscular dystrophy
CITATUZUMAB BOGATOXPhase I
Epithelial cell adhesion molecule binding agent
ELX-02Phase II
80S Ribosome modulator
cystic fibrosis
MT-3724Phase II
80S Ribosome inhibitor
diffuse large B-cell lymphoma
TELIMOMAB ARITOXPhase II
T-cell surface glycoprotein CD5 binding agent
hepatitis B virus infection
ZOLIMOMAB ARITOXPhase II
T-cell surface glycoprotein CD5 binding agent
arthritis
Related Genes
EEF1A1Protein interaction100%EEF1B2Protein interaction100%EEF1GProtein interaction100%EEF2Protein interaction100%EIF5AProtein interaction100%ETF1Protein interaction100%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
52%
Lung
51%
Liver
42%
Brain
27%
Heart
18%
Gene Interaction Network
Click a node to explore
RPSAEEF1A1EEF1B2EEF1GEEF2EIF5AETF1
PROTEIN STRUCTURE
Preparing viewer…
PDB8GLP Β· 1.67 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.14Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.00 [0.00–0.14]
RankingsWhere RPSA stands among ~20K protein-coding genes
  • #780of 20,598
    Most Researched384 Β· top 5%
  • #761of 1,025
    FDA-Approved Drug Targets1
  • #2,909of 5,498
    Most Pathogenic Variants9
  • #182of 17,882
    Most Constrained (LOEUF)0.14 Β· top 5%
Genes detectedRPSA
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
PMID: 30337486
Development Β· 2018
1.00
2
Upregulation of ribosome complexes at the blood-brain barrier in Alzheimer's disease patients.
PMID: 35766008
J Cereb Blood Flow Metab Β· 2022
0.90
3
Enolase of Streptococcus suis serotype 2 promotes biomolecular condensation of ribosomal protein SA for HBMECs apoptosis.
PMID: 38331785
BMC Biol Β· 2024
0.80
4
Rpsa Signaling Regulates Cortical Neuronal Morphogenesis via Its Ligand, PEDF, and Plasma Membrane Interaction Partner, Itga6.
PMID: 34347028
Cereb Cortex Β· 2022
0.70
5
Pyrazinamide resistance among multidrug-resistant tuberculosis clinical isolates in a national referral center of China and its correlations with pncA, rpsA, and panD gene mutations.
PMID: 26775806
Diagn Microbiol Infect Dis Β· 2016
0.68