Hermansky-Pudlak syndrome 5

Summary

Hermansky-Pudlak syndrome 5 (MONDO:0013557) is a disease caused by HPS5 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: HPS5 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 162

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Hermansky-Pudlak syndrome 5
Mondo ID	MONDO:0013557
OMIM	614074
DOID	DOID:0060543
UMLS	C3888004
MedGen	854711
GARD	0018334
Is cancer (heuristic)	no

Also known as: Hermansky-Pudlak syndrome 5 · Hermansky-Pudlak syndrome caused by mutation in HPS5 · Hermansky-Pudlak syndrome type 5 · HPS5 · HPS5 Hermansky-Pudlak syndrome

Data availability: 162 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 without pulmonary fibrosis › Hermansky-Pudlak syndrome 5

Related subtypes (2): Hermansky-Pudlak syndrome 3, 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

ClinVar germline variants

162 retrieved; paginated sample, class counts are floors:

68 uncertain significance, 22 conflicting classifications of pathogenicity, 20 pathogenic, 18 benign, 13 likely pathogenic, 8 benign/likely benign, 7 likely benign, 6 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1405318	NM_181507.2(HPS5):c.2077del (p.Arg693fs)	HPS5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1695385	NM_181507.2(HPS5):c.370C>T (p.Arg124Ter)	HPS5	Pathogenic	criteria provided, single submitter
21818	NM_181507.2(HPS5):c.2593C>T (p.Arg865Ter)	HPS5	Pathogenic	criteria provided, single submitter
21819	NM_181507.2(HPS5):c.2624del (p.Leu875fs)	HPS5	Pathogenic	no assertion criteria provided
21820	NM_181507.2(HPS5):c.2928_2929dup (p.Thr977fs)	HPS5	Pathogenic	criteria provided, multiple submitters, no conflicts
21822	NM_181507.2(HPS5):c.879dup (p.Lys294fs)	HPS5	Pathogenic	criteria provided, single submitter
2735562	NM_181507.2(HPS5):c.888dup (p.His297fs)	HPS5	Pathogenic	criteria provided, multiple submitters, no conflicts
2757438	NM_181507.2(HPS5):c.1252del (p.Glu418fs)	HPS5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2780208	NM_181507.2(HPS5):c.2718-2A>G	HPS5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280536	NM_181507.2(HPS5):c.2979_2982del (p.Cys993fs)	HPS5	Pathogenic	criteria provided, multiple submitters, no conflicts
3152	NM_181507.2(HPS5):c.2026_2029del (p.Val676fs)	HPS5	Pathogenic	no assertion criteria provided
3374732	NM_181507.2(HPS5):c.2275G>T (p.Gly759Ter)	HPS5	Pathogenic	no assertion criteria provided
3374733	NM_181507.2(HPS5):c.1128A>G (p.Thr376=)	HPS5	Pathogenic	no assertion criteria provided
427876	NM_181507.2(HPS5):c.1900del (p.Glu634fs)	HPS5	Pathogenic	no assertion criteria provided
427877	NM_181507.2(HPS5):c.3096_3098del (p.Leu1033del)	HPS5	Pathogenic	no assertion criteria provided
427878	NM_181507.2(HPS5):c.818_822del (p.Thr273fs)	HPS5	Pathogenic	criteria provided, single submitter
427879	NM_181507.2(HPS5):c.1417C>T (p.Gln473Ter)	HPS5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
427880	NM_181507.2(HPS5):c.2219T>C (p.Leu740Ser)	HPS5	Pathogenic	no assertion criteria provided
427881	NM_181507.2(HPS5):c.219G>A (p.Arg73=)	HPS5	Pathogenic	no assertion criteria provided
427882	NM_181507.2(HPS5):c.3058+3A>G	HPS5	Pathogenic	no assertion criteria provided
427883	NM_181507.2(HPS5):c.2750_2751del (p.Glu917fs)	HPS5	Pathogenic	no assertion criteria provided
427885	11p15.1 deletion	HPS5	Pathogenic	no assertion criteria provided
431164	NM_181507.2(HPS5):c.1423del (p.Leu475fs)	HPS5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
435459	NM_181507.2(HPS5):c.107del (p.Lys36fs)	HPS5	Pathogenic	criteria provided, single submitter
627032	NM_181507.2(HPS5):c.2036C>G (p.Ser679Ter)	HPS5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627333	NM_181507.2(HPS5):c.543del (p.Gln181fs)	HPS5	Pathogenic	criteria provided, multiple submitters, no conflicts
1339232	NM_181507.2(HPS5):c.1862+1G>A	HPS5	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1704626	NM_181507.2(HPS5):c.2837+1G>A	HPS5	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2503868	NM_181507.2(HPS5):c.478-2A>G	HPS5	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382311	NM_181507.2(HPS5):c.927_928del (p.Gly310fs)	HPS5	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
HPS5	Definitive	Autosomal recessive	Hermansky-Pudlak syndrome 5	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HPS5	Orphanet:231512	Hermansky-Pudlak syndrome due to BLOC-2 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
HPS5	HGNC:17022	ENSG00000110756	Q9UPZ3	BLOC-2 complex member HPS5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HPS5	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, HPS5, WD40_repeat_dom_sf

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
liver	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HPS5	134	ubiquitous	marker	sural nerve, male germ line stem cell (sensu Vertebrata) in testis, liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HPS5	664

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HPS5	Q9UPZ3	73.21

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
developmental pigmentation	1	2106.5×	0.002	HPS5
melanosome assembly	1	887.0×	0.002	HPS5
platelet dense granule organization	1	674.1×	0.002	HPS5
blood coagulation	1	173.7×	0.006	HPS5

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
HPS5	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	HPS5

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)
HPS5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.