Peeling skin syndrome 5

Summary

Peeling skin syndrome 5 (MONDO:0014923) is a disease caused by SERPINB8 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SERPINB8 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peeling skin syndrome 5
Mondo ID	MONDO:0014923
OMIM	617115
DOID	DOID:0070524
UMLS	C4310710
MedGen	934677
GARD	0018427
Is cancer (heuristic)	no

Also known as: peeling skin syndrome 5 · peeling skin syndrome 5; PSS5 · peeling skin syndrome caused by mutation in SERPINB8 · peeling skin syndrome type 5 · PSS5 · SERPINB8 peeling skin syndrome

Data availability: 9 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › epidermal disease › ichthyosis › inherited ichthyosis › autosomal recessive congenital ichthyosis › exfoliative ichthyosis › peeling skin syndrome 5

Related subtypes (2): superficial epidermolytic ichthyosis, peeling skin syndrome 4

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

9 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
254199	NM_002640.4(SERPINB8):c.2T>C (p.Met1Thr)	SERPINB8	Pathogenic	criteria provided, single submitter
2585175	NM_002640.4(SERPINB8):c.270del (p.Asn90fs)	SERPINB8	Likely pathogenic	criteria provided, single submitter
3780595	NM_002640.4(SERPINB8):c.820G>T (p.Glu274Ter)	SERPINB8	Likely pathogenic	criteria provided, single submitter
254200	NM_002640.4(SERPINB8):c.850C>T (p.Arg284Ter)	SERPINB8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
254198	NM_002640.4(SERPINB8):c.947del (p.Lys316fs)	SERPINB8	Uncertain significance	criteria provided, single submitter
1220688	NM_002640.4(SERPINB8):c.1076A>G (p.His359Arg)	SERPINB8	Benign	criteria provided, multiple submitters, no conflicts
1234066	NM_002640.4(SERPINB8):c.910A>G (p.Thr304Ala)	SERPINB8	Benign	criteria provided, multiple submitters, no conflicts
1262057	NM_002640.4(SERPINB8):c.203G>A (p.Arg68Gln)	SERPINB8	Benign	criteria provided, multiple submitters, no conflicts
1263303	NM_002640.4(SERPINB8):c.477G>A (p.Leu159=)	SERPINB8	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
SERPINB8	Strong	Autosomal recessive	peeling skin syndrome 5	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SERPINB8	Orphanet:263548	Peeling skin syndrome type A
SERPINB8	Orphanet:289586	Exfoliative ichthyosis

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
SERPINB8	HGNC:8952	ENSG00000166401	P50452	Serpin B8	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SERPINB8	Serpin B8	Has an important role in epithelial desmosome-mediated cell-cell adhesion.

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)
SERPINB8	Other/Unknown	no		Serpin_fam, Serpin_CS, Serpin_dom

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
monocyte	1
mononuclear cell	1
skin of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SERPINB8	185	ubiquitous	marker	monocyte, skin of leg, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SERPINB8	979

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SERPINB8	P50452	91.48

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Dissolution of Fibrin Clot	1	815.7×	0.002	SERPINB8
Hemostasis	1	36.0×	0.028	SERPINB8

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
negative regulation of endopeptidase activity	1	1685.2×	8e-04	SERPINB8
epithelial cell-cell adhesion	1	1203.7×	8e-04	SERPINB8

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 0

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
SERPINB8	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	SERPINB8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SERPINB8	6	Binding:6

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	SERPINB8

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	1	SERPINB8
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.