Psoriasis 15, pustular, susceptibility to

disease

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Also known as AP1S3 generalised pustular psoriasisAP1S3 generalized pustular psoriasisgeneralised pustular psoriasis caused by mutation in AP1S3generalized pustular psoriasis caused by mutation in AP1S3PSORS15

Summary

Psoriasis 15, pustular, susceptibility to (MONDO:0014494) is a disease caused by AP1S3 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: AP1S3 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	psoriasis 15, pustular, susceptibility to
Mondo ID	MONDO:0014494
OMIM	616106
DOID	DOID:0111281
UMLS	C4015235
MedGen	863672
Is cancer (heuristic)	no

Also known as: AP1S3 generalised pustular psoriasis · AP1S3 generalized pustular psoriasis · generalised pustular psoriasis caused by mutation in AP1S3 · generalized pustular psoriasis caused by mutation in AP1S3 · psoriasis 15, pustular, susceptibility to · PSORS15

Data availability: 4 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › psoriasis, susceptibility to › psoriasis 15, pustular, susceptibility to

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

4 retrieved; paginated sample, class counts are floors:

3 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1301563	NM_001039569.2(AP1S3):c.248T>C (p.Ile83Thr)	AP1S3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1301564	NM_001039569.2(AP1S3):c.64A>G (p.Thr22Ala)	AP1S3	Likely benign	criteria provided, multiple submitters, no conflicts
160375	NM_001039569.2(AP1S3):c.97C>T (p.Arg33Trp)	AP1S3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
160376	NM_001039569.2(AP1S3):c.11T>G (p.Phe4Cys)	AP1S3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
AP1S3	Strong	Autosomal dominant	psoriasis 15, pustular, susceptibility to	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AP1S3	Orphanet:163927	Pustulosis palmaris et plantaris
AP1S3	Orphanet:163931	Acrodermatitis continua of Hallopeau
AP1S3	Orphanet:247353	Generalized pustular psoriasis

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
AP1S3	HGNC:18971	ENSG00000152056	Q96PC3	AP-1 complex subunit sigma-3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AP1S3	AP-1 complex subunit sigma-3	Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes.

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)
AP1S3	Other/Unknown	no		Clathrin_sm-chain_CS, Longin-like_dom_sf, AP_complex_ssu

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
islet of Langerhans	1
male germ line stem cell (sensu Vertebrata) in testis	1
placenta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AP1S3	135	ubiquitous	marker	islet of Langerhans, placenta, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AP1S3	746

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AP1S3	Q96PC3	20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
Nef mediated downregulation of MHC class I complex cell surface expression	1	1142.0×	0.008	AP1S3
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	1	634.4×	0.008	AP1S3
The role of Nef in HIV-1 replication and disease pathogenesis	1	634.4×	0.008	AP1S3
Host Interactions of HIV factors	1	335.9×	0.010	AP1S3
Lysosome Vesicle Biogenesis	1	326.3×	0.010	AP1S3
trans-Golgi Network Vesicle Budding	1	253.8×	0.011	AP1S3
Golgi Associated Vesicle Biogenesis	1	200.3×	0.011	AP1S3
HIV Infection	1	119.0×	0.017	AP1S3
MHC class II antigen presentation	1	89.2×	0.020	AP1S3
Membrane Trafficking	1	37.1×	0.041	AP1S3
Vesicle-mediated transport	1	34.8×	0.041	AP1S3
Viral Infection Pathways	1	30.8×	0.041	AP1S3
Adaptive Immune System	1	29.8×	0.041	AP1S3
Infectious disease	1	24.8×	0.046	AP1S3
Disease	1	13.1×	0.077	AP1S3
Immune System	1	13.0×	0.077	AP1S3

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
melanosome assembly	1	887.0×	0.004	AP1S3
platelet dense granule organization	1	674.1×	0.004	AP1S3
protein targeting	1	366.4×	0.005	AP1S3
vesicle-mediated transport	1	96.3×	0.013	AP1S3
intracellular protein transport	1	64.8×	0.015	AP1S3

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
AP1S3	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	AP1S3

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)
AP1S3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: AP1S3