Pachyonychia congenita 1

Summary

Pachyonychia congenita 1 (MONDO:0008173) is a disease caused by KRT16 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: KRT16 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 25

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pachyonychia congenita 1
Mondo ID	MONDO:0008173
OMIM	167200
SNOMED CT	39427000
UMLS	C1706595
MedGen	353335
GARD	0015102
Is cancer (heuristic)	no

Also known as: Jadassohn-Lewandowsky syndrome · KRT16 pachyonychia congenita · pachyonychia congenita 1 · pachyonychia congenita caused by mutation in KRT16 · pachyonychia congenita type 1 · pachyonychia congenita, Jadassohn-Lewandowsky type · PC1

Data availability: 25 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 › keratosis › palmoplantar keratosis › hereditary palmoplantar keratoderma › focal palmoplantar keratoderma › pachyonychia congenita › pachyonychia congenita 1

Related subtypes (3): pachyonychia congenita 2, pachyonychia congenita 3, pachyonychia congenita 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

25 retrieved; paginated sample, class counts are floors:

11 pathogenic, 5 conflicting classifications of pathogenicity, 2 benign, 2 pathogenic/likely pathogenic, 2 likely pathogenic, 2 uncertain significance, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
14600	NM_005557.4(KRT16):c.395T>C (p.Leu132Pro)	KRT16	Pathogenic	criteria provided, single submitter
14601	NM_005557.4(KRT16):c.379C>T (p.Arg127Cys)	KRT16	Pathogenic	criteria provided, multiple submitters, no conflicts
14602	NM_005557.4(KRT16):c.374A>G (p.Asn125Ser)	KRT16	Pathogenic	criteria provided, multiple submitters, no conflicts
14603	NM_005557.4(KRT16):c.386CCT[1] (p.Ser130del)	KRT16	Pathogenic	criteria provided, single submitter
14604	NM_005557.4(KRT16):c.380G>C (p.Arg127Pro)	KRT16	Pathogenic	no assertion criteria provided
14605	NM_005557.4(KRT16):c.365A>C (p.Gln122Pro)	KRT16	Pathogenic	no assertion criteria provided
14606	NM_005557.4(KRT16):c.371T>G (p.Leu124Arg)	KRT16	Pathogenic	no assertion criteria provided
14608	NM_005557.4(KRT16):c.362T>C (p.Met121Thr)	KRT16	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14609	NM_005557.4(KRT16):c.383T>A (p.Leu128Gln)	KRT16	Pathogenic	no assertion criteria provided
156024	NM_005557.4(KRT16):c.373_374delinsGG (p.Asn125Gly)	KRT16	Pathogenic	no assertion criteria provided
265217	NM_005557.4(KRT16):c.379C>G (p.Arg127Gly)	KRT16	Pathogenic	criteria provided, multiple submitters, no conflicts
66605	NM_005557.4(KRT16):c.371T>A (p.Leu124His)	KRT16	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
66608	NM_005557.4(KRT16):c.373A>G (p.Asn125Asp)	KRT16	Pathogenic	criteria provided, single submitter
216955	NM_005557.4(KRT16):c.365A>G (p.Gln122Arg)	KRT16	Likely pathogenic	criteria provided, single submitter
3581944	NM_005557.4(KRT16):c.375T>G (p.Asn125Lys)	KRT16	Likely pathogenic	criteria provided, single submitter
1414941	NM_005557.4(KRT16):c.933+18del	KRT16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
14607	NM_005557.4(KRT16):c.1062A>T (p.Lys354Asn)	KRT16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3632758	NM_005557.4(KRT16):c.1225C>T (p.Arg409Trp)	KRT16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
587419	NM_005557.4(KRT16):c.539C>T (p.Ala180Val)	KRT16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
791432	NM_005557.4(KRT16):c.644C>G (p.Thr215Ser)	KRT16	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3581943	NM_005557.4(KRT16):c.822G>T (p.Met274Ile)	KRT16	Uncertain significance	criteria provided, single submitter
3891520	NM_005557.4(KRT16):c.737A>T (p.Glu246Val)	KRT16	Uncertain significance	criteria provided, single submitter
1264136	NM_005557.4(KRT16):c.624T>C (p.His208=)	KRT16	Benign	criteria provided, multiple submitters, no conflicts
1300085	NM_005557.4(KRT16):c.1281-16T>C	KRT16	Benign	criteria provided, multiple submitters, no conflicts
786318	NM_005557.4(KRT16):c.67G>A (p.Gly23Ser)	KRT16	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
KRT16	Strong	Autosomal dominant	pachyonychia congenita 1	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KRT16	Orphanet:2199	Epidermolytic palmoplantar keratoderma
KRT16	Orphanet:2309	Pachyonychia congenita
KRT16	Orphanet:448264	Isolated focal non-epidermolytic palmoplantar keratoderma

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
KRT16	HGNC:6423	ENSG00000186832	P08779	Keratin, type I cytoskeletal 16	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KRT16	Keratin, type I cytoskeletal 16	Epidermis-specific type I keratin that plays a key role in skin.

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)
KRT16	Other/Unknown	no		Keratin_I, IF_conserved, IF_rod_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
gingiva	1
gingival epithelium	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KRT16	176	broad	marker	gingival epithelium, gingiva, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRT16	2,175

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KRT16	P08779	74.26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Formation of the cornified envelope	1	87.8×	0.027	KRT16
Keratinization	1	55.7×	0.027	KRT16
Developmental Biology	1	14.5×	0.069	KRT16

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
keratinocyte migration	1	2407.4×	0.005	KRT16
hair cycle	1	936.2×	0.006	KRT16
establishment of skin barrier	1	455.5×	0.007	KRT16
morphogenesis of an epithelium	1	343.9×	0.007	KRT16
keratinocyte differentiation	1	247.8×	0.007	KRT16
intermediate filament organization	1	240.7×	0.007	KRT16
keratinization	1	234.1×	0.007	KRT16
cytoskeleton organization	1	132.7×	0.010	KRT16
negative regulation of cell migration	1	111.6×	0.011	KRT16
inflammatory response	1	37.7×	0.029	KRT16
innate immune response	1	33.6×	0.030	KRT16

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
KRT16	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	KRT16

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)
KRT16	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.