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

ENSG00000189114 ∙ NCBI:388552 ∙ OMIM:609762 ∙ HGNC:20914 ∙ Uniprot:Q6QNY0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the BLOC1S3 gene.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				76	5	81
missense			63	6		69
nonsense						0
start loss						0
frameshift						0
inframe indel			6			6
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	1	2	4
Total	0	0	70	83	7

Variants in BLOC1S3

This is a list of pathogenic ClinVar variants found in the BLOC1S3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-45179290-C-G		not specified	Benign (Aug 18, 2016)
19-45179296-C-T		BLOC1S3-related disorder	Likely benign (Feb 29, 2024)
19-45179301-C-T		Inborn genetic diseases	Uncertain significance (Nov 03, 2022)
19-45179302-G-A			Likely benign (Nov 19, 2023)
19-45179309-G-A		BLOC1S3-related disorder	Likely benign (Jan 21, 2024)
19-45179313-G-A			Uncertain significance (Apr 11, 2023)
19-45179327-C-T			Likely benign (Jan 06, 2023)
19-45179330-C-T		not specified	Uncertain significance (Aug 07, 2024)
19-45179332-G-A			Likely benign (Jun 09, 2023)
19-45179338-G-A			Likely benign (Dec 09, 2023)
19-45179344-G-A			Likely benign (May 20, 2023)
19-45179348-G-A			Uncertain significance (Feb 24, 2022)
19-45179352-C-T			Uncertain significance (Aug 10, 2022)
19-45179359-G-A			Likely benign (Apr 17, 2023)
19-45179362-G-A			Likely benign (Jan 10, 2024)
19-45179366-G-A			Uncertain significance (Oct 17, 2022)
19-45179368-G-A			Likely benign (Feb 08, 2023)
19-45179382-G-A			Uncertain significance (Jan 01, 2022)
19-45179382-G-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Mar 21, 2024)
19-45179382-G-T		Hermansky-Pudlak syndrome 8	Uncertain significance (-)
19-45179383-C-A			Likely benign (Jan 14, 2024)
19-45179385-C-G			Uncertain significance (Nov 14, 2022)
19-45179387-G-T		Inborn genetic diseases	Uncertain significance (Feb 10, 2022)
19-45179388-C-T		not specified • Inborn genetic diseases • BLOC1S3-related disorder	Conflicting classifications of pathogenicity (Aug 15, 2023)
19-45179389-G-T			Likely benign (Nov 15, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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