Hermansky-Pudlak syndrome 6

Summary

Hermansky-Pudlak syndrome 6 (MONDO:0013558) is a disease caused by HPS6 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: HPS6 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 114

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Hermansky-Pudlak syndrome 6
Mondo ID	MONDO:0013558
OMIM	614075
DOID	DOID:0060544
NCIT	C150369
UMLS	C3888007
MedGen	854714
GARD	0018335
Is cancer (heuristic)	no

Also known as: Hermansky-Pudlak syndrome 6 · Hermansky-Pudlak syndrome caused by mutation in HPS6 · Hermansky-Pudlak syndrome type 6 · HPS6 · HPS6 Hermansky-Pudlak syndrome

Data availability: 114 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.

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 6

Related subtypes (2): Hermansky-Pudlak syndrome 3, Hermansky-Pudlak syndrome 5

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

114 retrieved; paginated sample, class counts are floors:

41 uncertain significance, 19 conflicting classifications of pathogenicity, 16 pathogenic, 14 likely pathogenic, 12 pathogenic/likely pathogenic, 8 benign/likely benign, 3 benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
40972	nsv1067844		Pathogenic	no assertion criteria provided
1050563	NM_024747.6(HPS6):c.206_210dup (p.Trp71fs)	HPS6	Pathogenic	criteria provided, single submitter
1210214	NM_024747.6(HPS6):c.1030G>T (p.Glu344Ter)	HPS6	Pathogenic	criteria provided, multiple submitters, no conflicts
1323067	NM_024747.6(HPS6):c.1411C>T (p.Gln471Ter)	HPS6	Pathogenic	criteria provided, single submitter
1443600	NM_024747.6(HPS6):c.466_475dup (p.Phe159fs)	HPS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1691238	NM_024747.6(HPS6):c.1228_1252del (p.Tyr410fs)	HPS6	Pathogenic	criteria provided, single submitter
2136928	NM_024747.6(HPS6):c.1513C>T (p.Gln505Ter)	HPS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2152093	NM_024747.6(HPS6):c.1387C>T (p.Arg463Ter)	HPS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2418963	NM_024747.6(HPS6):c.503_504del (p.Leu168fs)	HPS6	Pathogenic	criteria provided, multiple submitters, no conflicts
2440763	NM_024747.6(HPS6):c.1789del (p.Ala597fs)	HPS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2693547	NM_024747.6(HPS6):c.27del (p.Leu10fs)	HPS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2958318	NM_024747.6(HPS6):c.1674del (p.Asn559fs)	HPS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2979661	NM_024747.6(HPS6):c.560dup (p.His187fs)	HPS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30671	NM_024747.6(HPS6):c.1065dup (p.Leu356fs)	HPS6	Pathogenic	no assertion criteria provided
30672	NM_024747.6(HPS6):c.1865_1866del (p.Leu622fs)	HPS6	Pathogenic	criteria provided, single submitter
30673	NM_024747.6(HPS6):c.913C>T (p.Gln305Ter)	HPS6	Pathogenic	criteria provided, single submitter
30676	NM_024747.6(HPS6):c.223C>T (p.Gln75Ter)	HPS6	Pathogenic	criteria provided, single submitter
30677	NM_024747.6(HPS6):c.1234C>T (p.Gln412Ter)	HPS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3151	NM_024747.6(HPS6):c.1714_1717del (p.Leu572fs)	HPS6	Pathogenic	no assertion criteria provided
3242587	NM_024747.6(HPS6):c.1942C>T (p.Gln648Ter)	HPS6	Pathogenic	no assertion criteria provided
3590239	NM_024747.6(HPS6):c.1784G>A (p.Trp595Ter)	HPS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
431050	NM_024747.6(HPS6):c.1898del (p.Pro633fs)	HPS6	Pathogenic	no assertion criteria provided
431051	NM_024747.6(HPS6):c.2038C>T (p.Gln680Ter)	HPS6	Pathogenic	criteria provided, single submitter
435465	NM_024747.6(HPS6):c.1711_1712insAG (p.Cys571Ter)	HPS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627011	NM_024747.6(HPS6):c.155del (p.Val52fs)	HPS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627382	NM_024747.6(HPS6):c.779G>A (p.Gly260Glu)	HPS6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
996366	NM_024747.6(HPS6):c.335G>A (p.Trp112Ter)	HPS6	Pathogenic	criteria provided, single submitter
996367	NM_024747.6(HPS6):c.1732C>T (p.Arg578Ter)	HPS6	Pathogenic	criteria provided, single submitter
2440755	NM_024747.6(HPS6):c.1136C>A (p.Ser379Ter)	HPS6	Likely pathogenic	criteria provided, single submitter
3064168	NM_024747.6(HPS6):c.877C>T (p.Gln293Ter)	HPS6	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
HPS6	Definitive	Autosomal recessive	Hermansky-Pudlak syndrome 6	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HPS6	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
HPS6	HGNC:18817	ENSG00000166189	Q86YV9	BLOC-2 complex member HPS6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 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)
HPS6	Other/Unknown	no		BLOC-2_complex_Hps6_subunit, HPS6_C, HPS6_N

Expression context

Cohort genes with no expression data: 0.

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
gingival epithelium	1
granulocyte	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HPS6	216	ubiquitous	yes	granulocyte, gingival epithelium, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HPS6	965

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HPS6	Q86YV9	77.54

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
melanosome assembly	1	887.0×	0.004	HPS6
platelet dense granule organization	1	674.1×	0.004	HPS6
protein localization to membrane	1	601.9×	0.004	HPS6
lysosome localization	1	526.6×	0.004	HPS6
lipid homeostasis	1	337.0×	0.005	HPS6
protein secretion	1	263.3×	0.005	HPS6
blood coagulation	1	173.7×	0.007	HPS6
lipid metabolic process	1	91.6×	0.011	HPS6

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
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: 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	HPS6

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)
HPS6	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.