BLOC1S5

biogenesis of lysosomal organelles complex 1 subunit 5, the group of Biogenesis of lysosomal organelles complex 1 subunits

Basic information

Region (hg38): 6:8013566-8064396

Previous symbols: [ "MUTED" ]

Links

ENSG00000188428 ∙ NCBI:63915 ∙ OMIM:607289 ∙ HGNC:18561 ∙ Uniprot:Q8TDH9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Hermansky-Pudlak syndrome (Moderate), mode of inheritance: AR
• Hermansky-Pudlak syndrome 11 (Moderate), mode of inheritance: AR
• Hermansky-Pudlak syndrome 11 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hermansky-Pudlak syndrome 11	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; Hematologic; Ophthalmologic	32565547

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BLOC1S5 gene.

• Inborn genetic diseases (10 variants)
• not provided (1 variants)
• Hermansky-Pudlak syndrome 11 (1 variants)
• BLOC1S5-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BLOC1S5 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		1
missense			8	2		10
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region						0
non coding						0
Total	0	2	8	3	0

Highest pathogenic variant AF is 0.0000131

Variants in BLOC1S5

This is a list of pathogenic ClinVar variants found in the BLOC1S5 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-8015668-G-A		Inborn genetic diseases	Uncertain significance (Dec 04, 2023)
6-8015710-T-C		Inborn genetic diseases	Likely benign (Feb 10, 2022)
6-8026378-C-G		Inborn genetic diseases	Uncertain significance (Sep 14, 2021)
6-8026405-CT-C		Hermansky-Pudlak syndrome • Hermansky-Pudlak syndrome 11	Pathogenic (Jan 29, 2021)
6-8026427-T-G		BLOC1S5-related disorder	Likely pathogenic (Mar 13, 2023)
6-8041169-G-A		Inborn genetic diseases	Uncertain significance (Dec 03, 2021)
6-8041181-T-C		Inborn genetic diseases	Uncertain significance (Jan 20, 2023)
6-8041213-T-C		Inborn genetic diseases	Uncertain significance (Nov 21, 2023)
6-8041235-C-T		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
6-8041262-G-A		Inborn genetic diseases	Uncertain significance (Oct 06, 2023)
6-8041263-T-A		Inborn genetic diseases	Uncertain significance (Aug 16, 2021)
6-8054272-T-C		BLOC1S5-related disorder	Likely benign (Aug 26, 2021)
6-8062556-C-T		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
6-8062559-G-A		Inborn genetic diseases	Uncertain significance (May 30, 2023)
6-8062574-AC-A		Hermansky-Pudlak syndrome 11	Likely pathogenic (Apr 28, 2022)
6-8064269-G-C		Inborn genetic diseases	Uncertain significance (Feb 27, 2023)
6-8064319-T-C		Inborn genetic diseases	Likely benign (Feb 13, 2023)
6-8064327-C-T		Inborn genetic diseases	Uncertain significance (Oct 02, 2023)
6-8064352-G-A		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
6-8064353-G-A			Likely benign (Nov 01, 2022)
6-8064358-C-A		Hermansky-Pudlak syndrome 11	Likely pathogenic (Sep 23, 2022)
6-8064375-A-C		Hermansky-Pudlak syndrome 11	Pathogenic (Mar 26, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BLOC1S5	protein_coding	protein_coding	ENST00000397457	5	50848

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.85e-9	0.0466	125670	1	76	125747	0.000306

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.250	109	102	1.07	0.00000505	1244
Missense in Polyphen		28	25.941	1.0794		345
Synonymous	-0.274	35	33.0	1.06	0.00000150	325
Loss of Function	-0.569	12	10.1	1.19	5.89e-7	114

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00123	0.00123
Ashkenazi Jewish	0.00	0.00
East Asian	0.000386	0.000381
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000213	0.000211
Middle Eastern	0.000386	0.000381
South Asian	0.000132	0.000131
Other	0.000176	0.000163

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:17182842}.

Recessive Scores

• pRec: 0.258

Intolerance Scores

• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.58

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.166
• ghis: 0.435

Essentials

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

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Bloc1s5
• Phenotype: renal/urinary system phenotype; vision/eye phenotype; hearing/vestibular/ear phenotype; pigmentation phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular 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)

Gene ontology

• Biological process: anterograde axonal transport;neuron projection development;melanosome transport;melanosome organization;endosome to melanosome transport;anterograde synaptic vesicle transport;positive regulation of pigment cell differentiation
• Cellular component: transport vesicle;BLOC-1 complex;axon cytoplasm
• Molecular function: protein binding