Hermansky-Pudlak syndrome 10

Summary

Hermansky-Pudlak syndrome 10 (MONDO:0014885) is a disease caused by AP3D1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: AP3D1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Hermansky-Pudlak syndrome 10
Mondo ID	MONDO:0014885
OMIM	617050
Orphanet	664511
UMLS	C4310746
MedGen	934713
GARD	0016180
Is cancer (heuristic)	no

Also known as: AP3D1 Hermansky-Pudlak syndrome · Hermansky-Pudlak syndrome 10 · Hermansky-Pudlak syndrome 10; HPS10 · Hermansky-Pudlak syndrome caused by mutation in AP3D1 · Hermansky-Pudlak syndrome type 10 · HPS10

Data availability: 15 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 10

Related subtypes (8): Hermansky-Pudlak syndrome 2, Hermansky-Pudlak syndrome 7, Hermansky-Pudlak syndrome 8, Hermansky-Pudlak syndrome 9, 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

15 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
253144	NM_001261826.3(AP3D1):c.3565_3566del (p.Val1189fs)	AP3D1	Pathogenic	no assertion criteria provided
1099332	NM_001261826.3(AP3D1):c.3233A>G (p.Lys1078Arg)	AP3D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3583551	NM_001261826.3(AP3D1):c.2131G>A (p.Val711Ile)	AP3D1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1353985	NM_001261826.3(AP3D1):c.3148G>A (p.Val1050Ile)	AP3D1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1434996	NM_001261826.3(AP3D1):c.349C>T (p.Arg117Cys)	AP3D1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1440018	NM_001261826.3(AP3D1):c.3637G>A (p.Ala1213Thr)	AP3D1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1497556	NM_001261826.3(AP3D1):c.2001+6C>T	AP3D1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1507429	NM_001261826.3(AP3D1):c.3493T>G (p.Cys1165Gly)	AP3D1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1675095	NM_001261826.3(AP3D1):c.2601+6G>T	AP3D1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3238617	NM_001261826.3(AP3D1):c.3134C>T (p.Ser1045Phe)	AP3D1	Uncertain significance	criteria provided, single submitter
3583550	NM_001261826.3(AP3D1):c.3072G>C (p.Lys1024Asn)	AP3D1	Uncertain significance	criteria provided, single submitter
4071535	NM_001261826.3(AP3D1):c.1803_1859+5del	AP3D1	Uncertain significance	criteria provided, single submitter
988866	NM_001261826.3(AP3D1):c.1363G>A (p.Ala455Thr)	AP3D1	Uncertain significance	criteria provided, multiple submitters, no conflicts
724796	NM_001261826.3(AP3D1):c.463-4G>A	AP3D1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
737118	NM_001261826.3(AP3D1):c.2832G>A (p.Glu944=)	AP3D1	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 3 · 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
AP3D1	Strong	Autosomal recessive	Hermansky-Pudlak syndrome 10	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AP3D1	Orphanet:1000	Ocular albinism with late-onset sensorineural deafness
AP3D1	Orphanet:54	X-linked recessive ocular albinism
AP3D1	Orphanet:664511	Early-onset severe Hermansky-Pudlak syndrome with hearing loss, due to AP3D1 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
AP3D1	HGNC:568	ENSG00000065000	O14617	AP-3 complex subunit delta-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AP3D1	AP-3 complex subunit delta-1	Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated.

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)
AP3D1	Other/Unknown	no		Clathrin/coatomer_adapt-like_N, AP3D_dom_metazoa, ARM-like

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
adenohypophysis	1
pituitary gland	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AP3D1	295	ubiquitous	marker	tendon of biceps brachii, adenohypophysis, pituitary gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AP3D1	2,108

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AP3D1	O14617	6

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
neurotransmitter receptor transport, postsynaptic endosome to lysosome	1	8426.0×	0.001	AP3D1
synaptic vesicle budding from endosome	1	5617.3×	0.001	AP3D1
positive regulation of NK T cell differentiation	1	4213.0×	0.001	AP3D1
zinc ion import into lysosome	1	4213.0×	0.001	AP3D1
synaptic vesicle coating	1	3370.4×	0.001	AP3D1
synaptic vesicle membrane organization	1	3370.4×	0.001	AP3D1
clathrin-coated vesicle cargo loading, AP-3-mediated	1	2407.4×	0.001	AP3D1
antigen processing and presentation, exogenous lipid antigen via MHC class Ib	1	2407.4×	0.001	AP3D1
Golgi to vacuole transport	1	1872.4×	0.001	AP3D1
endosome to melanosome transport	1	1685.2×	0.001	AP3D1
protein targeting to vacuole	1	1296.3×	0.001	AP3D1
synaptic vesicle recycling	1	1203.7×	0.001	AP3D1
anterograde synaptic vesicle transport	1	991.3×	0.002	AP3D1
melanosome assembly	1	887.0×	0.002	AP3D1
platelet dense granule organization	1	674.1×	0.002	AP3D1
melanosome organization	1	648.1×	0.002	AP3D1
protein localization to membrane	1	601.9×	0.002	AP3D1
anterograde axonal transport	1	581.1×	0.002	AP3D1
vesicle-mediated transport	1	96.3×	0.011	AP3D1
intracellular protein transport	1	64.8×	0.016	AP3D1
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	AP3D1

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
AP3D1	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
AP3D1	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	AP3D1

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)
AP3D1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.