Hermansky-Pudlak syndrome 8
disease diseaseOn this page
Also known as BLOC1S3 Hermansky-Pudlak syndromeHermansky-Pudlak syndrome caused by mutation in BLOC1S3Hermansky-Pudlak syndrome type 8HPS8
Summary
Hermansky-Pudlak syndrome 8 (MONDO:0013560) is a disease caused by BLOC1S3 (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: BLOC1S3 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 11
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Hermansky-Pudlak syndrome 8 |
| Mondo ID | MONDO:0013560 |
| OMIM | 614077 |
| Orphanet | 231537 |
| DOID | DOID:0060546 |
| UMLS | C3888026 |
| MedGen | 854728 |
| GARD | 0018337 |
| Is cancer (heuristic) | no |
Also known as: BLOC1S3 Hermansky-Pudlak syndrome · Hermansky-Pudlak syndrome 8 · Hermansky-Pudlak syndrome caused by mutation in BLOC1S3 · Hermansky-Pudlak syndrome type 8 · HPS8
Data availability: 11 ClinVar variants · 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic oculocutaneous albinism › Hermansky-Pudlak syndrome › Hermansky-Pudlak syndrome 8
Related subtypes (8): Hermansky-Pudlak syndrome 2, Hermansky-Pudlak syndrome 7, Hermansky-Pudlak syndrome 9, Hermansky-Pudlak syndrome 10, Hermansky-Pudlak syndrome with pulmonary fibrosis, Hermansky-Pudlak syndrome without pulmonary fibrosis, Kotzot-Richter syndrome, Hermansky-Pudlak syndrome 11
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
11 retrieved; paginated sample, class counts are floors:
5 pathogenic, 4 uncertain significance, 1 benign, 1 conflicting classifications of pathogenicity
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1489 | NM_212550.5(BLOC1S3):c.448del (p.Gln150fs) | BLOC1S3 | Pathogenic | no assertion criteria provided |
| 431167 | NM_212550.5(BLOC1S3):c.131C>A (p.Ser44Ter) | BLOC1S3 | Pathogenic | no assertion criteria provided |
| 870134 | NM_212550.5(BLOC1S3):c.444_467del (p.Gln150_Ala157del) | BLOC1S3 | Pathogenic | no assertion criteria provided |
| 870630 | NM_212550.5(BLOC1S3):c.338_341del (p.Leu113fs) | BLOC1S3 | Pathogenic | no assertion criteria provided |
| 929862 | NM_212550.5(BLOC1S3):c.385_403del (p.Ser129fs) | BLOC1S3 | Pathogenic | no assertion criteria provided |
| 1703821 | NM_212550.5(BLOC1S3):c.86G>T (p.Arg29Leu) | BLOC1S3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1033706 | NM_212550.5(BLOC1S3):c.505G>T (p.Ala169Ser) | BLOC1S3 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1379818 | NM_212550.5(BLOC1S3):c.335G>T (p.Arg112Leu) | BLOC1S3 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1432959 | NM_212550.5(BLOC1S3):c.449A>G (p.Gln150Arg) | BLOC1S3 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3893002 | NM_212550.5(BLOC1S3):c.87dup (p.Ser30fs) | BLOC1S3 | Uncertain significance | criteria provided, single submitter |
| 162790 | NM_212550.5(BLOC1S3):c.270G>A (p.Ala90=) | BLOC1S3 | Benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| BLOC1S3 | Strong | Autosomal recessive | Hermansky-Pudlak syndrome 8 | 3 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| BLOC1S3 | Orphanet:231531 | Hermansky-Pudlak syndrome due to BLOC-1 deficiency |
Cohort genes → proteins
1 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| BLOC1S3 | HGNC:20914 | ENSG00000189114 | Q6QNY0 | Biogenesis of lysosome-related organelles complex 1 subunit 3 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| BLOC1S3 | Biogenesis of lysosome-related organelles complex 1 subunit 3 | 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. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Other/Unknown | 1 | 1.8× | 0.558 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| BLOC1S3 | Other/Unknown | no | BLOC-1_complex_su-3 |
Expression context
Cohort genes with no expression data: 0.
1 cohort gene are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 1 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| oocyte | 1 |
| secondary oocyte | 1 |
| upper arm skin | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| BLOC1S3 | 225 | ubiquitous | marker | oocyte, secondary oocyte, upper arm skin |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| BLOC1S3 | 604 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| BLOC1S3 | Q6QNY0 | 71.38 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| trans-Golgi Network Vesicle Budding | 1 | 253.8× | 0.010 | BLOC1S3 |
| Golgi Associated Vesicle Biogenesis | 1 | 200.3× | 0.010 | BLOC1S3 |
| Membrane Trafficking | 1 | 37.1× | 0.029 | BLOC1S3 |
| Vesicle-mediated transport | 1 | 34.8× | 0.029 | BLOC1S3 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| secretion of lysosomal enzymes | 1 | 3370.4× | 0.002 | BLOC1S3 |
| positive regulation of natural killer cell activation | 1 | 2106.5× | 0.002 | BLOC1S3 |
| endosome to melanosome transport | 1 | 1685.2× | 0.002 | BLOC1S3 |
| anterograde synaptic vesicle transport | 1 | 991.3× | 0.002 | BLOC1S3 |
| melanosome transport | 1 | 766.0× | 0.002 | BLOC1S3 |
| pigmentation | 1 | 702.2× | 0.002 | BLOC1S3 |
| platelet dense granule organization | 1 | 674.1× | 0.002 | BLOC1S3 |
| melanosome organization | 1 | 648.1× | 0.002 | BLOC1S3 |
| anterograde axonal transport | 1 | 581.1× | 0.002 | BLOC1S3 |
| eye development | 1 | 351.1× | 0.004 | BLOC1S3 |
| platelet activation | 1 | 267.5× | 0.004 | BLOC1S3 |
| neuron projection development | 1 | 122.1× | 0.009 | BLOC1S3 |
| response to xenobiotic stimulus | 1 | 69.1× | 0.014 | BLOC1S3 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| BLOC1S3 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | BLOC1S3 |
Undrugged target profiles
1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| BLOC1S3 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: BLOC1S3