Hermansky-Pudlak syndrome 11

Summary

Hermansky-Pudlak syndrome 11 (MONDO:0030903) is a disease caused by BLOC1S5 (GenCC Strong), with 1 cohort gene and 6 clinical trials. Top therapeutic interventions include erythromycin, pirfenidone, and pravastatin.

At a glance

• Causal gene: BLOC1S5 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 6
• Clinical trials: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Hermansky-Pudlak syndrome 11
Mondo ID	MONDO:0030903
OMIM	619172
UMLS	C5436936
MedGen	1727728
GARD	0018339
Is cancer (heuristic)	no

Also known as: Hermansky-Pudlak syndrome · HPS11

Data availability: 6 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 11

Related subtypes (8): Hermansky-Pudlak syndrome 2, Hermansky-Pudlak syndrome 7, Hermansky-Pudlak syndrome 8, Hermansky-Pudlak syndrome 9, Hermansky-Pudlak syndrome 10, Hermansky-Pudlak syndrome with pulmonary fibrosis, Hermansky-Pudlak syndrome without pulmonary fibrosis, Kotzot-Richter syndrome

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

6 retrieved; paginated sample, class counts are floors:

3 likely pathogenic, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3065169	NM_201280.3(BLOC1S5):c.2T>G (p.Met1Arg)	BLOC1S5	Pathogenic	criteria provided, single submitter
870631	NM_201280.3(BLOC1S5):c.345del (p.Val116fs)	BLOC1S5	Pathogenic	no assertion criteria provided
996012	NM_201280.2:c.196-678_384+3483del	BLOC1S5	Pathogenic	no assertion criteria provided
2431939	NM_201280.3(BLOC1S5):c.19G>T (p.Glu7Ter)	BLOC1S5	Likely pathogenic	criteria provided, single submitter
3236053	NM_201280.3(BLOC1S5):c.154del (p.Val52fs)	BLOC1S5	Likely pathogenic	criteria provided, single submitter
4845846	NM_201280.3(BLOC1S5):c.352A>T (p.Arg118Ter)	BLOC1S5	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
BLOC1S5	Strong	Autosomal recessive	Hermansky-Pudlak syndrome 11	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BLOC1S5	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
BLOC1S5	HGNC:18561	ENSG00000188428	Q8TDH9	Biogenesis of lysosome-related organelles complex 1 subunit 5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BLOC1S5	Biogenesis of lysosome-related organelles complex 1 subunit 5	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)
BLOC1S5	Other/Unknown	no		Bloc1s5

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
kidney epithelium	1
pancreatic ductal cell	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BLOC1S5	257	ubiquitous	marker	pancreatic ductal cell, visceral pleura, kidney epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BLOC1S5	768

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BLOC1S5	Q8TDH9	87.86

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
positive regulation of pigment cell differentiation	1	8426.0×	0.001	BLOC1S5
otolith morphogenesis	1	3370.4×	0.001	BLOC1S5
endosome to melanosome transport	1	1685.2×	0.002	BLOC1S5
anterograde synaptic vesicle transport	1	991.3×	0.002	BLOC1S5
melanosome transport	1	766.0×	0.002	BLOC1S5
melanosome organization	1	648.1×	0.002	BLOC1S5
anterograde axonal transport	1	581.1×	0.002	BLOC1S5
neuron projection development	1	122.1×	0.009	BLOC1S5
vesicle-mediated transport	1	96.3×	0.010	BLOC1S5

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BLOC1S5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
BLOC1S5	6	Binding:6

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	BLOC1S5

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)
BLOC1S5	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE1/PHASE2	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00467831	PHASE1/PHASE2	TERMINATED	Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
NCT04193592	PHASE2	UNKNOWN	Efficacy and Safety of Pirfenidone Treatment in HPS-ILD
NCT00001456	Not specified	RECRUITING	Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome
NCT00084305	Not specified	ACTIVE_NOT_RECRUITING	Analysis of Specimens From Individuals With Pulmonary Fibrosis
NCT01417520	Not specified	COMPLETED	Clinical and Pathophysiological Investigations Into Erdheim Chester Disease
NCT02368340	Not specified	COMPLETED	A Longitudinal Study of Hermansky-Pudlak Syndrome Pulmonary Fibrosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ERYTHROMYCIN	4	1
PIRFENIDONE	4	1
PRAVASTATIN	4	1
ZILEUTON	4	1
CHEMBL5435500	0	1