BLOC1S1
protein-codingbiogenesis of lysosomal organelles complex 1 subunit 1, the group of BLOC-1 related complex subunits|Biogenesis of lysosomal organelles complex 1 subunits
Gene summary
BLOC1S1 is a component of the ubiquitously expressed BLOC1 multisubunit protein complex. BLOC1 is required for normal biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense granules (Starcevic and Dell'Angelica, 2004 [PubMed 15102850]).[supplied by OMIM, Mar 2008]
- GCN5L1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0700092
Submitter: ClinGen
*BLOC1S1* (Biogenesis of Lysosome-Related Organelles Complex 1 Subunit 1) is located at chromosome 12 at 12q13.2 and encodes a protein that is part of the BORC and BLOC-1 complexes. *BLOC1S1* localizes to the surface of lysosomes and is necessary for endosomal sorting, vesicular trafficking, and keeping lysosomes properly positioned. Affected patients primarily present with hypomyelinating leukodystrophy with epileptic encephalopathy, spasticity, hypotonia, optic atrophy, and hypopigmentation. These variants impair normal lysosomal and autophagic functions in the brain. Six variants (five missense, one splice site) across three publications have been included in this curation (PMIDs: 33875846, 36070637; 41887224). The mechanism of disease is loss-of-function. This gene-disease relationship is also supported by experimental evidence including a mouse model, Drosophila model, and biochemical function evidence (PMIDs: 25898163, 25183008, 20015953). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Syndromic disease GCEP on the meeting date April 1, 2026 (SOP Version 12).
Inheritance Pattern: AR
Disease ID:MONDO:0100038
Submitter: Illumina
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to BLOC1S1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001487.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 29 | 29 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 29 | 0 | 0 | 29 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001478.2 | 4 | MANE Select | |
| Ensembl | ENSP00000447537.1 | 4 | MANE Select | |
| Ensembl | ENSP00000448605.1 | 2 | Standard | |
| Ensembl | ENSP00000450218.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| bloc1s1 | Danio rerio | Structure: iridophore Quality: lacks all parts of type abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Golgi Associated Vesicle Biogenesis
- Lysosome Vesicle Biogenesis
- Clathrin derived vesicle budding
- trans-Golgi Network Vesicle Budding
- Vesicle-mediated transport
Biological Process
- anterograde axonal transport
- aerobic respiration
- endosomal transport
- peptidyl-lysine acetylation
- neuron projection development
Molecular Function
- protein binding
Cellular Component
- extracellular space
- mitochondrial intermembrane space
- mitochondrial matrix
- lysosomal membrane
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000548925
- Coding exons
- 4
- Length
- 4052
- Individuals with no LoFs
- 125740
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125746
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0339 | 86 | 85.1 | 1.01 | 0.00000420 | 982 |
| Missense (PolyPhen) | 16 | 22.481 | 0.71172 | 318 | ||
| Synonymous | -0.558 | 38 | 33.9 | 1.12 | 0.00000162 | 303 |
| Loss of Function | 1.65 | 3 | 8.05 | 0.373 | 3.90e-7 | 80 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension (PubMed:17182842). As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor (PubMed:25898167). {ECO:0000269|PubMed:17182842, ECO:0000269|PubMed:25898167}.;
Recessive Scores
- pRec
- 0.136
Intolerance Scores
- LoFtool
- 0.452
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.992
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |