Hermansky-Pudlak syndrome without pulmonary fibrosis

Summary

Hermansky-Pudlak syndrome without pulmonary fibrosis (MONDO:0016502) is a disease with 3 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Hermansky-Pudlak syndrome without pulmonary fibrosis
Mondo ID	MONDO:0016502
Orphanet	231512
ICD-11	1363499932
UMLS	C5679833
MedGen	1842321
GARD	0017169
Is cancer (heuristic)	no

Also known as: HPS without pulmonary fibrosis

Data availability: 3 GenCC gene-disease records · 1 cell line.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic oculocutaneous albinism › Hermansky-Pudlak syndrome › Hermansky-Pudlak syndrome without pulmonary fibrosis

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, Kotzot-Richter syndrome, Hermansky-Pudlak syndrome 11

Subtypes (3): Hermansky-Pudlak syndrome 3, Hermansky-Pudlak syndrome 5, Hermansky-Pudlak syndrome 6

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 3 · 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
HPS3	Definitive	Autosomal recessive	Hermansky-Pudlak syndrome 3	4
HPS5	Definitive	Autosomal recessive	Hermansky-Pudlak syndrome 5	4
HPS6	Definitive	Autosomal recessive	Hermansky-Pudlak syndrome 6	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HPS3	Orphanet:231512	Hermansky-Pudlak syndrome due to BLOC-2 deficiency
HPS5	Orphanet:231512	Hermansky-Pudlak syndrome due to BLOC-2 deficiency
HPS6	Orphanet:231512	Hermansky-Pudlak syndrome due to BLOC-2 deficiency

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HPS3	HGNC:15597	ENSG00000163755	Q969F9	BLOC-2 complex member HPS3	gencc
HPS5	HGNC:17022	ENSG00000110756	Q9UPZ3	BLOC-2 complex member HPS5	gencc
HPS6	HGNC:18817	ENSG00000166189	Q86YV9	BLOC-2 complex member HPS6	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HPS3	BLOC-2 complex member HPS3	Involved in early stages of melanosome biogenesis and maturation.
HPS5	BLOC-2 complex member HPS5	May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules.
HPS6	BLOC-2 complex member HPS6	May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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
Scaffold/PPI	1	5.8×	0.327
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HPS3	Other/Unknown	no		HPS3, HPS3_N, HPS3_C
HPS5	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, HPS5, WD40_repeat_dom_sf
HPS6	Other/Unknown	no		BLOC-2_complex_Hps6_subunit, HPS6_C, HPS6_N

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ileal mucosa	1
jejunal mucosa	1
secondary oocyte	1
liver	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1
gingival epithelium	1
granulocyte	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HPS3	245	ubiquitous	marker	ileal mucosa, secondary oocyte, jejunal mucosa
HPS5	134	ubiquitous	marker	sural nerve, male germ line stem cell (sensu Vertebrata) in testis, liver
HPS6	216	ubiquitous	yes	granulocyte, gingival epithelium, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HPS6	965
HPS3	768
HPS5	664

Intra-cohort edges

A	B	Sources
HPS3	HPS5	intact, string_interaction
HPS3	HPS6	biogrid_interaction, intact, string_interaction
HPS5	HPS6	biogrid_interaction, intact, string_interaction

Structural data

PDB: 0 · AlphaFold-only: 3 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HPS3	Q969F9	82.67
HPS6	Q86YV9	77.54
HPS5	Q9UPZ3	73.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
melanosome assembly	3	887.0×	1e-08	HPS3, HPS5, HPS6
platelet dense granule organization	3	674.1×	1e-08	HPS3, HPS5, HPS6
blood coagulation	2	115.8×	3e-04	HPS5, HPS6
developmental pigmentation	1	702.2×	0.004	HPS5
pigmentation	1	234.1×	0.008	HPS3
protein localization to membrane	1	200.6×	0.008	HPS6
lysosome localization	1	175.5×	0.008	HPS6
lipid homeostasis	1	112.3×	0.011	HPS6
protein secretion	1	87.8×	0.013	HPS6
lipid metabolic process	1	30.5×	0.032	HPS6

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HPS3	0	0
HPS5	0	0
HPS6	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
HPS6	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	HPS3, HPS5, HPS6

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
HPS3	0	—
HPS5	0	—
HPS6	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.