BLOC1S3
biogenesis of lysosomal organelles complex 1 subunit 3, the group of Biogenesis of lysosomal organelles complex 1 subunits
Basic information
Region (hg38): 19:45178784-45216933
Links
Phenotypes
GenCC
Source:
- Hermansky-Pudlak syndrome 8 (Strong), mode of inheritance: AR
- Hermansky-Pudlak syndrome 8 (Strong), mode of inheritance: AR
- Hermansky-Pudlak syndrome 8 (Moderate), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hermansky-Pudlak syndrome 8 | AR | Allergy/Immunology/Infectious; Dermatologic; Hematologic; Ophthalmologic | Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Surveillance related to ophthalmologic and other manifestations has been recommended in all individuals with HPS | Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic | 16385460; 20301464 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (154 variants)
- Inborn_genetic_diseases (37 variants)
- not_specified (19 variants)
- BLOC1S3-related_disorder (13 variants)
- Hermansky-Pudlak_syndrome_8 (10 variants)
- Hermansky-Pudlak_syndrome (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the BLOC1S3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000212550.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 85 | 88 | ||||
| missense | 79 | 88 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 4 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 5 | 0 | 80 | 94 | 3 |
Highest pathogenic variant AF is 0.00013268206
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| BLOC1S3 | protein_coding | protein_coding | ENST00000433642 | 1 | 3057 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00408 | 0.435 | 104680 | 0 | 1 | 104681 | 0.00000478 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.334 | 97 | 88.2 | 1.10 | 0.00000427 | 1198 |
| Missense in Polyphen | 26 | 22.681 | 1.1464 | 328 | ||
| Synonymous | -0.108 | 44 | 43.1 | 1.02 | 0.00000227 | 494 |
| Loss of Function | -0.432 | 3 | 2.29 | 1.31 | 1.01e-7 | 37 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000102 | 0.0000102 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
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. Plays a role in intracellular vesicle trafficking. {ECO:0000269|PubMed:16385460, ECO:0000269|PubMed:17182842}.;
- Disease
- DISEASE: Hermansky-Pudlak syndrome 8 (HPS8) [MIM:614077]: A form of Hermansky-Pudlak syndrome, a genetically heterogeneous autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS. {ECO:0000269|PubMed:16385460}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Golgi Associated Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking
(Consensus)
Recessive Scores
- pRec
- 0.239
Haploinsufficiency Scores
- pHI
- 0.0538
- hipred
- N
- hipred_score
- 0.272
- ghis
- 0.680
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.958
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Bloc1s3
- Phenotype
- craniofacial phenotype; cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); pigmentation phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; vision/eye phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype;
Gene ontology
- Biological process
- eye development;anterograde axonal transport;platelet activation;neuron projection development;melanosome transport;melanosome organization;positive regulation of natural killer cell activation;secretion of lysosomal enzymes;endosome to melanosome transport;response to drug;pigmentation;anterograde synaptic vesicle transport;platelet dense granule organization;protein transmembrane transport
- Cellular component
- cytosol;transport vesicle;BLOC-1 complex;axon cytoplasm
- Molecular function
- molecular_function;protein binding;protein transmembrane transporter activity