Hermansky-Pudlak syndrome 7

Summary

Hermansky-Pudlak syndrome 7 (MONDO:0013559) is a disease caused by DTNBP1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: DTNBP1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 13

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		9	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Hermansky-Pudlak syndrome 7
Mondo ID	MONDO:0013559
OMIM	614076
Orphanet	231531
DOID	DOID:0060545
UMLS	C3279756
MedGen	481386
GARD	0018336
Is cancer (heuristic)	no

Also known as: DTNBP1 Hermansky-Pudlak syndrome · Hermansky-Pudlak syndrome 7 · Hermansky-Pudlak syndrome caused by mutation in DTNBP1 · Hermansky-Pudlak syndrome type 7 · HPS7

Data availability: 13 ClinVar variants · 4 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 7

Related subtypes (8): Hermansky-Pudlak syndrome 2, Hermansky-Pudlak syndrome 8, Hermansky-Pudlak syndrome 9, Hermansky-Pudlak syndrome 10, Hermansky-Pudlak syndrome with pulmonary fibrosis, Hermansky-Pudlak syndrome without pulmonary fibrosis, Kotzot-Richter syndrome, Hermansky-Pudlak syndrome 11

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

13 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 3 likely benign, 2 pathogenic, 2 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
162098	NM_032122.5(DTNBP1):c.177G>A (p.Trp59Ter)	DTNBP1	Pathogenic	no assertion criteria provided
2068358	NM_032122.5(DTNBP1):c.79_83del (p.Ser27fs)	DTNBP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3432	NM_032122.5(DTNBP1):c.307C>T (p.Gln103Ter)	DTNBP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1698876	NM_032122.5(DTNBP1):c.872T>G (p.Leu291Ter)	DTNBP1	Likely pathogenic	criteria provided, single submitter
4081356	NM_032122.5(DTNBP1):c.502dup (p.Thr168fs)	DTNBP1	Likely pathogenic	criteria provided, single submitter
1032266	NM_032122.5(DTNBP1):c.488+18G>A	DTNBP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1195511	NM_032122.5(DTNBP1):c.811+42C>T	DTNBP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2500235	NM_032122.5(DTNBP1):c.111-2A>G	DTNBP1	Uncertain significance	no assertion criteria provided
98378	NM_032122.5(DTNBP1):c.654T>G (p.Ile218Met)	DTNBP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1575214	NM_032122.5(DTNBP1):c.355+10A>G	DTNBP1	Likely benign	criteria provided, multiple submitters, no conflicts
1615910	NM_032122.5(DTNBP1):c.512-16T>C	DTNBP1	Likely benign	criteria provided, multiple submitters, no conflicts
163300	NM_032122.5(DTNBP1):c.811+96G>A	DTNBP1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
98379	NM_032122.5(DTNBP1):c.324C>T (p.Ile108=)	DTNBP1	Likely benign	criteria provided, multiple submitters, no conflicts

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
DTNBP1	Definitive	Autosomal recessive	Hermansky-Pudlak syndrome 7	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DTNBP1	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
DTNBP1	HGNC:17328	ENSG00000047579	Q96EV8	Dysbindin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DTNBP1	Dysbindin	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)
DTNBP1	Other/Unknown	no		Dysbindin

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
nucleus accumbens	1
putamen	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DTNBP1	249	ubiquitous	marker	tendon of biceps brachii, nucleus accumbens, putamen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DTNBP1	1,501

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DTNBP1	Q96EV8	75.92

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Golgi Associated Vesicle Biogenesis	1	200.3×	0.005	DTNBP1

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
positive regulation of glutamate neurotransmitter secretion in response to membrane depolarization	1	8426.0×	0.002	DTNBP1
regulation of dopamine receptor signaling pathway	1	4213.0×	0.002	DTNBP1
negative regulation of dendritic spine morphogenesis	1	3370.4×	0.002	DTNBP1
positive regulation of neurotransmitter secretion	1	1872.4×	0.003	DTNBP1
protein transmembrane transport	1	1296.3×	0.003	DTNBP1
regulation of dopamine secretion	1	1203.7×	0.003	DTNBP1
anterograde synaptic vesicle transport	1	991.3×	0.003	DTNBP1
positive regulation of receptor internalization	1	702.2×	0.004	DTNBP1
platelet dense granule organization	1	674.1×	0.004	DTNBP1
melanosome organization	1	648.1×	0.004	DTNBP1
anterograde axonal transport	1	581.1×	0.004	DTNBP1
regulation of synaptic vesicle exocytosis	1	455.5×	0.004	DTNBP1
dendrite morphogenesis	1	432.1×	0.004	DTNBP1
neuron projection morphogenesis	1	276.3×	0.006	DTNBP1
regulation of signal transduction	1	267.5×	0.006	DTNBP1
retina development in camera-type eye	1	255.3×	0.006	DTNBP1
memory	1	183.2×	0.007	DTNBP1
blood coagulation	1	173.7×	0.007	DTNBP1
kidney development	1	140.4×	0.009	DTNBP1
neuron projection development	1	122.1×	0.009	DTNBP1
actin cytoskeleton organization	1	79.1×	0.014	DTNBP1
cilium assembly	1	73.6×	0.014	DTNBP1
positive regulation of gene expression	1	38.7×	0.026	DTNBP1

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
DTNBP1	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	DTNBP1

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)
DTNBP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.