BLOC1S6

Chr 15

biogenesis of lysosomal organelles complex 1 subunit 6

Also known as: BLOS6, HPS9, PA, PALLID, PLDN

NCBI Gene: 26258 ENSG00000104164 UniProt: Q9UL45

The protein is a component of the BLOC-1 complex required for biogenesis of lysosome-related organelles such as platelet dense granules and melanosomes, and targets membrane protein cargos into vesicles for delivery to neurites and nerve terminals. Mutations cause Hermansky-Pudlak syndrome 9, which follows autosomal recessive inheritance and involves oculocutaneous albinism, bleeding diathesis, and pulmonary fibrosis. The gene shows low constraint to loss-of-function variation.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene may play a role in intracellular vesicle trafficking. It interacts with Syntaxin 13 which mediates intracellular membrane fusion. Mutations in this gene cause symptoms associated with Hermansky-Pudlak syndrome-9. Alternative splicing results in multiple transcript variants. A pseudogene related to this gene is located on the X chromosome. [provided by RefSeq, Aug 2015]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHermansky-Pudlak syndrome 9

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Hermansky-Pudlak syndrome 9 · AR · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.69

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — BLOC1S6

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.69LOEUF

pLI 0.000

Z-score -0.21

OE 1.07 (0.68–1.69)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.86Z-score

OE missense 0.74 (0.60–0.91)

64 obs / 86.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.07 (0.68–1.69)

0≤0.351.4

Missense OE?0.74 (0.60–0.91)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 12 / 11.2Missense obs/exp: 64 / 86.5Syn Z: 0.13

Background carrier burden — how many people carry a rare variant somewhere in BLOC1S6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 310

250 rare PASS variants

Rare truncating (LoF)

1 in 2,100

62 rare PASS variants

Rare synonymous (reference)

1 in 890

103 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BLOC1S6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 510	1 in 3,300
South Asian	~43k	1 in 190	1 in 1,300
Remaining (unassigned)	~30k	1 in 210	1 in 410
European (Finnish)	~27k	1 in 2,200	1 in 620
Admixed American	~22k	1 in 150	1 in 820
African / African American	~21k	1 in 360	1 in 1,800
East Asian	~20k	1 in 270	1 in 860
Ashkenazi Jewish	~13k	1 in 1,100	1 in 490
Middle Eastern	~2,884	1 in 260	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 5 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 5.? see exons ↓