Hermansky-Pudlak syndrome with pulmonary fibrosis

Summary

Hermansky-Pudlak syndrome with pulmonary fibrosis (MONDO:0016501) is a disease with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 2
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Hermansky-Pudlak syndrome with pulmonary fibrosis
Mondo ID	MONDO:0016501
Orphanet	231500
ICD-11	1086187623
UMLS	C5679834
MedGen	1843223
GARD	0017168
Is cancer (heuristic)	no

Also known as: HPS with pulmonary fibrosis

Data availability: 1 ClinVar variant · 2 GenCC gene-disease records · 8 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › respiratory system disorder › lower respiratory tract disorder › lung disorder › interstitial lung disease › interstitial lung disease specific to childhood › Hermansky-Pudlak syndrome with pulmonary fibrosis

Related subtypes (4): Niemann-Pick disease type B, primary interstitial lung disease specific to childhood, familial hypocalciuric hypercalcemia, congenital emphysematous lung disease due to Filamin A loss-of-function variant

Subtypes (2): Hermansky-Pudlak syndrome 1, Hermansky-Pudlak syndrome 4

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1072016	NM_000195.5(HPS1):c.1090dup (p.Leu364fs)	HPS1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 2 · 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
HPS1	Definitive	Autosomal recessive	Hermansky-Pudlak syndrome 1	4
HPS4	Definitive	Autosomal recessive	Hermansky-Pudlak syndrome 4	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HPS1	Orphanet:231500	Hermansky-Pudlak syndrome due to BLOC-3 deficiency
HPS4	Orphanet:231500	Hermansky-Pudlak syndrome due to BLOC-3 deficiency

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HPS1	HGNC:5163	ENSG00000107521	Q92902	BLOC-3 complex member HPS1	gencc,clinvar
HPS4	HGNC:15844	ENSG00000100099	Q9NQG7	BLOC-3 complex member HPS4	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HPS1	BLOC-3 complex member HPS1	Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into an active GTP-bound form.
HPS4	BLOC-3 complex member HPS4	Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into an active GTP-bound form.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HPS1	Other/Unknown	no		HPS1, FUZ/MON1/HPS1_longin_3, FUZ/MON1/HPS1_longin_2
HPS4	Other/Unknown	no		HPS4, CCZ1/INTU/HSP4_longin_1, CCZ1/INTU/HSP4_longin_3

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
small intestine Peyer’s patch	1
stromal cell of endometrium	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HPS1	231	ubiquitous	marker	granulocyte, stromal cell of endometrium, small intestine Peyer’s patch
HPS4	261	ubiquitous	marker	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HPS4	623
HPS1	409

Intra-cohort edges

A	B	Sources
HPS1	HPS4	intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HPS1	Q92902	1
HPS4	Q9NQG7	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RAB GEFs exchange GTP for GDP on RABs	2	124.1×	6e-05	HPS1, HPS4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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	2	887.0×	1e-05	HPS1, HPS4
platelet dense granule organization	2	674.1×	1e-05	HPS1, HPS4
lysosome organization	2	306.4×	4e-05	HPS1, HPS4
positive regulation of eye pigmentation	1	8426.0×	3e-04	HPS4
vesicle-mediated transport	2	96.3×	3e-04	HPS1, HPS4
hemostasis	1	842.6×	0.002	HPS4
melanocyte differentiation	1	401.2×	0.004	HPS4
obsolete positive regulation of protein targeting to mitochondrion	1	247.8×	0.006	HPS4
protein targeting	1	183.2×	0.007	HPS4
blood coagulation	1	86.9×	0.014	HPS4
visual perception	1	39.8×	0.027	HPS1
protein stabilization	1	33.4×	0.030	HPS4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
HPS1	0	0
HPS4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	HPS1, HPS4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
HPS1	0	—
HPS4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.