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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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BLOC1S1
biogenesis of lysosomal organelles complex 1 subunit 1
Chromosome 12 · 12q13.2
NCBI Gene: 2647Ensembl: ENSG00000135441.9HGNC: HGNC:4200UniProt: P78537
55PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GO:0005615mitochondrial matrixprotein-lysine-acetyltransferase activityaerobic respirationSevere intellectual disabilityepilepsySevere global developmental delayneurodegenerative disease
✦AI Summary

BLOC1S1 encodes a subunit of both the BLOC-1 and BORC complexes that regulate endolysosomal processes and lysosome-related organelle biogenesis 1. The protein functions as a protein acetyltransferase, negatively regulating aerobic respiration through mitochondrial protein lysine-acetylation and counteracting SIRT3 deacetylase activity 2. BLOC1S1 is essential for anterograde lysosome transport and autophagy function in both non-neuronal cells and neurons 1. The protein also modulates hepatic lysosomal content and lysosomal lipolysis, influencing cellular lipid storage independent of autophagy pathways 3. Structurally, BLOC1S1 contributes to BLOC-1's hetero-octameric architecture as part of the BLOC1S1/3/4/6 hemicomplex that forms the characteristic arc-shaped complex 4. Loss-of-function mutations in BLOC1S1 cause a neurological disorder characterized by early psychomotor delay, hypotonia, spasticity, epileptic encephalopathy, and leuko-axonopathy with hypomyelination, establishing BORCopathies as a distinct disease entity 1. Some patients also exhibit hypopigmentation features similar to Hermansky-Pudlak syndrome, though typically milder 1. These findings demonstrate BLOC1S1's critical role in multiple cellular processes including mitochondrial metabolism, lysosomal function, and neurological development.

Sources cited
1
BLOC1S1 is a subunit of BLOC-1 and BORC complexes, essential for lysosome transport and autophagy, and mutations cause neurological disorders with leuko-axonopathy
PMID: 40791729
2
BLOC1S1 functions as a protein acetyltransferase regulating mitochondrial protein acetylation and aerobic respiration
PMID: 38639088
3
BLOC1S1 modulates hepatic lysosomal content and lysosomal lipolysis, affecting cellular lipid storage
PMID: 36535215
4
BLOC1S1 is part of the BLOC1S1/3/4/6 hemicomplex contributing to BLOC-1's arc-shaped hetero-octameric architecture
PMID: 40279797
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
epilepsyOpen Targets
0.50Moderate
Severe global developmental delayOpen Targets
0.50Moderate
Severe intellectual disabilityOpen Targets
0.50Moderate
neurodegenerative diseaseOpen Targets
0.30Weak
myopiaOpen Targets
0.29Weak
age-related macular degenerationOpen Targets
0.29Weak
HypermetropiaOpen Targets
0.27Weak
COVID-19Open Targets
0.26Weak
retinopathyOpen Targets
0.26Weak
degeneration of macula and posterior poleOpen Targets
0.23Weak
macular degenerationOpen Targets
0.23Weak
Abnormality of refractionOpen Targets
0.23Weak
refractive errorOpen Targets
0.22Weak
eye diseaseOpen Targets
0.19Weak
wet macular degenerationOpen Targets
0.19Weak
atrophic macular degenerationOpen Targets
0.16Weak
lens diseaseOpen Targets
0.16Weak
Progressive visual lossOpen Targets
0.16Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HPS6Protein interaction100%HPS3Protein interaction100%LAMTOR4Protein interaction100%VAMP2Protein interaction100%HPS4Protein interaction99%BCAS4Protein interaction86%
Tissue Expression6 tissues
Liver
100%
Brain
77%
Lung
67%
Bone Marrow
56%
Ovary
55%
Heart
52%
Gene Interaction Network
Click a node to explore
BLOC1S1HPS6HPS3LAMTOR4VAMP2HPS4BCAS4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P78537
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.97LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.59 [0.37–0.97]
RankingsWhere BLOC1S1 stands among ~20K protein-coding genes
  • #8,171of 20,598
    Most Researched55
  • #9,236of 17,882
    Most Constrained (LOEUF)0.97
Genes detectedBLOC1S1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Increased LCN2 (lipocalin 2) in the RPE decreases autophagy and activates inflammasome-ferroptosis processes in a mouse model of dry AMD.
PMID: 35473441
Autophagy · 2023
1.00
2
Mitochondrial CypD Acetylation Promotes Endothelial Dysfunction and Hypertension.
PMID: 38639088
Circ Res · 2024
0.90
3
Combining exome/genome sequencing with data repository analysis reveals novel gene-disease associations for a wide range of genetic disorders.
PMID: 33875846
Genet Med · 2021
0.80
4
Generation of human induced pluripotential stem cells from individuals with complex heterozygous, isogenic corrected, and homozygous Bloc1s1 mutations.
PMID: 36070637
Stem Cell Res · 2022
0.70
5
PMID: 40791729
medRxiv · 2025
0.60