Bleeding and platelet disorders

Gene: BLOC1S5

Amber List (moderate evidence)

BLOC1S5 (biogenesis of lysosomal organelles complex 1 subunit 5)
EnsemblGeneIds (GRCh38): ENSG00000188428
EnsemblGeneIds (GRCh37): ENSG00000188428
OMIM: 607289, Gene2Phenotype
BLOC1S5 is in 3 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Two unrelated patients with this mild form of HPS. Rating Amber awaiting further publications with additional cases or clinical evidence supporting this gene-disease association.
Created: 7 Oct 2020, 11:35 a.m. | Last Modified: 7 Oct 2020, 11:35 a.m.
Panel Version: 1.12
- PMID: 32565547 (2020) - Patient 1 (20 years old) was initially diagnosed only with oculocutaneous albinism, but secondarily reported mild bleeding diathesis characterised by easy bruising and infrequent episodes of epistaxis and gingival bleeding. Patient 2 (39 years old) reported menorrhagia and excessive blood loss after deliveries and surgery. Further analyses documented in both patients a lack of detectable platelet dense granules, concomitant with mildly impaired activation-induced ATP release and platelet aggregation in vitro.
Created: 7 Oct 2020, 11:22 a.m. | Last Modified: 7 Oct 2020, 11:22 a.m.
Panel Version: 1.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hermansky–Pudlak syndrome

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

2 unrelated patients with mild oculocutaneous albinism, moderate bleeding diathesis, platelet aggregation deficit, and a dramatically decreased number of platelet dense granules, all signs compatible with HPS. Identified distinct homozygous variants in the BLOC1S5 gene (patient 1: deletion of exons 3 and 4, patient 2: 1-bp deletion in exon 4). Parental segregation confirmatory in patient 1, quantitative PCR analysis confirmatory in patient 2).

Functional tests performed on platelets of one patient displayed an absence of the obligate multisubunit complex BLOC-1, showing that the variant disrupts BLOC1S5 function and impairs BLOC-1 assembly. Expression of the patient-derived BLOC1S5 deletion in nonpigmented murine Bloc1s5-/- melan-mu melanocytes failed to rescue pigmentation, the assembly of a functional BLOC-1 complex, and melanosome cargo trafficking, unlike the wild-type allele.

Pathogenic variants in the genes encoding three other BLOC-1 subunits (DTNBP1, BLOC1S3, and BLOC1S6) underlie HPS types 7, 8, and 9 respectively.
Sources: Literature
Created: 5 Oct 2020, 9:11 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hermansky–Pudlak syndrome

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Hermansky–Pudlak syndrome
OMIM
607289
Clinvar variants
Variants in BLOC1S5
Penetrance
None
Publications
Panels with this gene

History Filter Activity

7 Oct 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: bloc1s5 has been classified as Amber List (Moderate Evidence).

5 Oct 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: BLOC1S5 was added gene: BLOC1S5 was added to Bleeding and platelet disorders. Sources: Literature Mode of inheritance for gene: BLOC1S5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BLOC1S5 were set to 32565547 Phenotypes for gene: BLOC1S5 were set to Hermansky–Pudlak syndrome Review for gene: BLOC1S5 was set to GREEN gene: BLOC1S5 was marked as current diagnostic