Hermansky-Pudlak syndrome 9

Summary

Hermansky-Pudlak syndrome 9 (MONDO:0013606) is a disease caused by BLOC1S6 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: BLOC1S6 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 181

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Hermansky-Pudlak syndrome 9
Mondo ID	MONDO:0013606
OMIM	614171
Orphanet	280663
DOID	DOID:0060547
UMLS	C3280026
MedGen	481656
GARD	0018338
Is cancer (heuristic)	no

Also known as: BLOC1S6 Hermansky-Pudlak syndrome · Hermansky-Pudlak syndrome 9 · Hermansky-Pudlak syndrome caused by mutation in BLOC1S6 · Hermansky-Pudlak syndrome type 9 · HPS9

Data availability: 181 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › hereditary hemophagocytic lymphohistiocytosis › Hermansky-Pudlak syndrome 9

Related subtypes (10): Chediak-Higashi syndrome, familial hemophagocytic lymphohistiocytosis type 1, familial hemophagocytic lymphohistiocytosis 4, familial hemophagocytic lymphohistiocytosis 2, Griscelli syndrome type 2, Hermansky-Pudlak syndrome 2, familial hemophagocytic lymphohistiocytosis 3, familial hemophagocytic lymphohistiocytosis 5, hemophagocytic lymphohistiocytosis, familial, 6, hemophagocytic lymphohistiocytosis due to RhoG deficiency

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

181 retrieved; paginated sample, class counts are floors:

82 likely benign, 61 uncertain significance, 18 pathogenic, 8 likely pathogenic, 5 benign, 3 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1701258	NM_012388.4(BLOC1S6):c.318_320delinsAT (p.Glu107fs)	BLOC1S6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1947585	NM_012388.4(BLOC1S6):c.261dup (p.Glu88fs)	BLOC1S6	Pathogenic	criteria provided, single submitter
1952947	NM_012388.4(BLOC1S6):c.89del (p.Ser30fs)	BLOC1S6	Pathogenic	criteria provided, single submitter
2742147	NM_012388.4(BLOC1S6):c.88del (p.Ser30fs)	BLOC1S6	Pathogenic	criteria provided, single submitter
2744373	NM_012388.4(BLOC1S6):c.157del (p.Ala53fs)	BLOC1S6	Pathogenic	criteria provided, single submitter
2748432	NM_012388.4(BLOC1S6):c.296T>A (p.Leu99Ter)	BLOC1S6	Pathogenic	criteria provided, single submitter
2828478	NM_012388.4(BLOC1S6):c.33_34del (p.Ala12fs)	BLOC1S6	Pathogenic	criteria provided, single submitter
2828875	NM_012388.4(BLOC1S6):c.245T>A (p.Leu82Ter)	BLOC1S6	Pathogenic	criteria provided, single submitter
2875941	NM_012388.4(BLOC1S6):c.7_22dup (p.Ser8fs)	BLOC1S6	Pathogenic	criteria provided, single submitter
2990226	NM_012388.4(BLOC1S6):c.203_207del (p.Lys68fs)	BLOC1S6	Pathogenic	criteria provided, single submitter
30412	NM_012388.4(BLOC1S6):c.232C>T (p.Gln78Ter)	BLOC1S6	Pathogenic	criteria provided, single submitter
3243821	NC_000015.9:g.(?45884313)(45898712_?)del	BLOC1S6	Pathogenic	criteria provided, single submitter
3335910	NM_012388.4(BLOC1S6):c.285_286dup (p.His96fs)	BLOC1S6	Pathogenic	no assertion criteria provided
3335913	NM_012388.4(BLOC1S6):c.148G>T (p.Glu50Ter)	BLOC1S6	Pathogenic	no assertion criteria provided
3335914	NM_012388.4(BLOC1S6):c.351dup (p.Ile118fs)	BLOC1S6	Pathogenic	no assertion criteria provided
3643922	NC_000015.10:g.45592135del	BLOC1S6	Pathogenic	criteria provided, single submitter
4073708	NM_012388.4(BLOC1S6):c.205C>T (p.Gln69Ter)	BLOC1S6	Pathogenic	criteria provided, single submitter
4077108	NM_012388.4(BLOC1S6):c.224+1G>A	BLOC1S6	Pathogenic	criteria provided, single submitter
827680	NM_012388.4(BLOC1S6):c.200C>G (p.Ser67Ter)	BLOC1S6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
996272	NM_012388.4(BLOC1S6):c.335dup (p.His112fs)	BLOC1S6	Pathogenic	criteria provided, multiple submitters, no conflicts
1933969	NM_012388.4(BLOC1S6):c.312+1G>T	BLOC1S6	Likely pathogenic	criteria provided, single submitter
2415699	NM_012388.4(BLOC1S6):c.82+1G>T	BLOC1S6	Likely pathogenic	criteria provided, single submitter
2584834	NM_012388.4(BLOC1S6):c.32_34delinsA (p.Gly11fs)	BLOC1S6	Likely pathogenic	criteria provided, single submitter
2708479	NM_012388.4(BLOC1S6):c.82+1_82+8del	BLOC1S6	Likely pathogenic	criteria provided, single submitter
2719871	NM_012388.4(BLOC1S6):c.313-1G>A	BLOC1S6	Likely pathogenic	criteria provided, single submitter
2791183	NM_012388.4(BLOC1S6):c.82+1G>A	BLOC1S6	Likely pathogenic	criteria provided, single submitter
3577240	NM_012388.4(BLOC1S6):c.83-1G>A	BLOC1S6	Likely pathogenic	criteria provided, single submitter
827679	NM_012388.4(BLOC1S6):c.319_320delinsAT (p.Glu107Met)	BLOC1S6	Likely pathogenic	criteria provided, single submitter
1060079	NM_012388.4(BLOC1S6):c.130A>G (p.Ile44Val)	BLOC1S6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1444501	NM_012388.4(BLOC1S6):c.332_333del (p.Tyr111fs)	BLOC1S6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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
BLOC1S6	Strong	Autosomal recessive	Hermansky-Pudlak syndrome 9	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BLOC1S6	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
BLOC1S6	HGNC:8549	ENSG00000104164	Q9UL45	Biogenesis of lysosome-related organelles complex 1 subunit 6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BLOC1S6	Biogenesis of lysosome-related organelles complex 1 subunit 6	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)
BLOC1S6	Other/Unknown	no		BLOC-1_pallidin, Snapin/Pallidin/Snn1

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
colonic epithelium	1
epithelial cell of pancreas	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BLOC1S6	262	ubiquitous	marker	epithelial cell of pancreas, colonic epithelium, pancreatic ductal cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BLOC1S6	1,227

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BLOC1S6	Q9UL45	84.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
trans-Golgi Network Vesicle Budding	1	253.8×	0.010	BLOC1S6
Golgi Associated Vesicle Biogenesis	1	200.3×	0.010	BLOC1S6
Membrane Trafficking	1	37.1×	0.029	BLOC1S6
Vesicle-mediated transport	1	34.8×	0.029	BLOC1S6

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
bradykinin biosynthetic process	1	16852.0×	0.001	BLOC1S6
circadian sleep/wake cycle	1	16852.0×	0.001	BLOC1S6
positive regulation of pigment cell differentiation	1	8426.0×	0.002	BLOC1S6
intracellular nitric oxide homeostasis	1	5617.3×	0.002	BLOC1S6
secretion of lysosomal enzymes	1	3370.4×	0.002	BLOC1S6
adenosine metabolic process	1	2407.4×	0.002	BLOC1S6
positive regulation of natural killer cell activation	1	2106.5×	0.002	BLOC1S6
response to acetylcholine	1	2106.5×	0.002	BLOC1S6
endosome to melanosome transport	1	1685.2×	0.002	BLOC1S6
endothelium development	1	1296.3×	0.002	BLOC1S6
L-glutamine metabolic process	1	1296.3×	0.002	BLOC1S6
obsolete synaptic vesicle docking	1	1296.3×	0.002	BLOC1S6
protein transmembrane transport	1	1296.3×	0.002	BLOC1S6
glutamate metabolic process	1	1123.5×	0.003	BLOC1S6
hypothalamus development	1	1053.2×	0.003	BLOC1S6
anterograde synaptic vesicle transport	1	991.3×	0.003	BLOC1S6
respiratory system process	1	936.2×	0.003	BLOC1S6
melanocyte differentiation	1	802.5×	0.003	BLOC1S6
melanosome transport	1	766.0×	0.003	BLOC1S6
homeostasis of number of cells	1	674.1×	0.003	BLOC1S6
melanosome organization	1	648.1×	0.003	BLOC1S6
dentate gyrus development	1	624.1×	0.003	BLOC1S6
membrane fusion	1	624.1×	0.003	BLOC1S6
anterograde axonal transport	1	581.1×	0.003	BLOC1S6
ATP metabolic process	1	468.1×	0.003	BLOC1S6
actin filament bundle assembly	1	455.5×	0.003	BLOC1S6
protein targeting	1	366.4×	0.004	BLOC1S6
vasodilation	1	366.4×	0.004	BLOC1S6
lung alveolus development	1	351.1×	0.004	BLOC1S6
phospholipid metabolic process	1	343.9×	0.004	BLOC1S6

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
BLOC1S6	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	BLOC1S6

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)
BLOC1S6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.