BLOC1S6

biogenesis of lysosomal organelles complex 1 subunit 6, the group of Biogenesis of lysosomal organelles complex 1 subunits

Basic information

Region (hg38): 15:45587213-45615945

Previous symbols: [ "PA", "PLDN" ]

Links

ENSG00000104164 ∙ NCBI:26258 ∙ OMIM:604310 ∙ HGNC:8549 ∙ Uniprot:Q9UL45 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Hermansky-Pudlak syndrome 9 (Strong), mode of inheritance: AR
• Hermansky-Pudlak syndrome 9 (Strong), mode of inheritance: AR
• Hermansky-Pudlak syndrome 9 (Supportive), mode of inheritance: AR
• Hermansky-Pudlak syndrome 9 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hermansky-Pudlak syndrome 9	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	21665000; 20301464; 22461475

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BLOC1S6 gene.

• Hermansky-Pudlak syndrome 9 (124 variants)
• not provided (15 variants)
• not specified (5 variants)
• Hermansky-Pudlak syndrome (5 variants)
• Inborn genetic diseases (5 variants)
• BLOC1S6-related condition (2 variants)
• Autoinflammatory syndrome (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BLOC1S6 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			1	28		29
missense		1	48	1		50
nonsense	3	1	1			5
start loss			1			1
frameshift	4	1	4			9
inframe indel						0
splice donor/acceptor (+/-2bp)		4				4
splice region			3	3	2	8
non coding			5	17	11	33
Total	7	7	60	46	11

Highest pathogenic variant AF is 0.0000394

Variants in BLOC1S6

This is a list of pathogenic ClinVar variants found in the BLOC1S6 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-45587446-G-A		Hermansky-Pudlak syndrome 9	Uncertain significance (Jun 06, 2021)
15-45587447-A-AGTGTCCCTGGGCCGTC		Hermansky-Pudlak syndrome 9	Pathogenic (Apr 17, 2023)
15-45587457-G-A		Hermansky-Pudlak syndrome 9	Uncertain significance (May 12, 2021)
15-45587457-G-T		Hermansky-Pudlak syndrome 9	Uncertain significance (Aug 12, 2021)
15-45587464-G-A		Hermansky-Pudlak syndrome 9	Likely benign (Jun 17, 2023)
15-45587468-C-T		Hermansky-Pudlak syndrome 9	Uncertain significance (Aug 04, 2023)
15-45587473-CGG-C		Hermansky-Pudlak syndrome 9	Pathogenic (May 28, 2023)
15-45587475-GGG-A		Hermansky-Pudlak syndrome 9	Likely pathogenic (-)
15-45587477-G-A		not specified • Hermansky-Pudlak syndrome 9	Benign/Likely benign (Jan 31, 2024)
15-45587479-C-T		Hermansky-Pudlak syndrome 9	Likely benign (Dec 09, 2023)
15-45587482-G-A		Hermansky-Pudlak syndrome 9	Likely benign (Sep 15, 2022)
15-45587486-C-A		Hermansky-Pudlak syndrome 9	Likely benign (Sep 21, 2023)
15-45587486-C-T		Hermansky-Pudlak syndrome 9	Uncertain significance (Feb 05, 2022)
15-45587488-G-A		Hermansky-Pudlak syndrome 9	Likely benign (Oct 31, 2023)
15-45587490-C-T		Hermansky-Pudlak syndrome 9	Uncertain significance (Jul 18, 2022)
15-45587494-C-G		Hermansky-Pudlak syndrome 9 • BLOC1S6-related disorder	Likely benign (Jan 18, 2024)
15-45587494-C-T		Hermansky-Pudlak syndrome 9	Likely benign (Apr 18, 2023)
15-45587506-G-A		Hermansky-Pudlak syndrome 9	Likely benign (Jan 27, 2023)
15-45587509-C-T		Hermansky-Pudlak syndrome 9	Likely benign (Nov 17, 2023)
15-45587511-G-A		Hermansky-Pudlak syndrome 9 • Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
15-45587512-G-A		Hermansky-Pudlak syndrome 9	Likely benign (Jan 13, 2020)
15-45587512-G-C		Hermansky-Pudlak syndrome 9	Likely benign (Nov 24, 2023)
15-45587515-G-A		Hermansky-Pudlak syndrome 9	Likely benign (Oct 28, 2021)
15-45587518-G-A		Hermansky-Pudlak syndrome 9	Likely benign (Jan 14, 2021)
15-45587522-C-T		Hermansky-Pudlak syndrome 9 • Inborn genetic diseases	Uncertain significance (Dec 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BLOC1S6	protein_coding	protein_coding	ENST00000220531	5	28877

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.04e-9	0.0844	125715	0	27	125742	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.859	64	86.5	0.740	0.00000386	1115
Missense in Polyphen		30	36.06	0.83195		512
Synonymous	0.132	32	33.0	0.971	0.00000146	307
Loss of Function	-0.211	12	11.2	1.07	6.71e-7	130

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000322	0.000322
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.000218	0.000217
South Asian	0.000294	0.000294
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. May play a role in intracellular vesicle trafficking, particularly in the vesicle-docking and fusion process. {ECO:0000269|PubMed:17182842, ECO:0000269|PubMed:21998198}.
• Disease: DISEASE: Hermansky-Pudlak syndrome 9 (HPS9) [MIM:614171]: 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:21665000}. 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: 0.232

Intolerance Scores

• rvis_EVS: 0.13
• rvis_percentile_EVS: 62.74

Haploinsufficiency Scores

• pHI: 0.0616
• hipred: N
• hipred_score: 0.383
• ghis: 0.618

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Medium
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Bloc1s6
• Phenotype: respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; skeleton phenotype; renal/urinary system 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); growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: anterograde axonal transport;synaptic vesicle docking;neuron projection development;melanosome transport;melanosome organization;endosome to melanosome transport;anterograde synaptic vesicle transport;positive regulation of pigment cell differentiation
• Cellular component: cytoplasm;cytosol;extrinsic component of membrane;transport vesicle;BLOC-1 complex;SNARE complex;presynapse;axon cytoplasm
• Molecular function: protein binding;syntaxin binding;identical protein binding;protein homodimerization activity;actin filament binding