Dermatopathia pigmentosa reticularis

Summary

Dermatopathia pigmentosa reticularis (MONDO:0007445) is a disease caused by KRT14 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: KRT14 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		20	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	dermatopathia pigmentosa reticularis
Mondo ID	MONDO:0007445
MeSH	C535374
OMIM	125595
Orphanet	86920
DOID	DOID:0111342
SNOMED CT	239088003
UMLS	C0406778
MedGen	98037
GARD	0008550
Is cancer (heuristic)	no

Also known as: dermatopathia pigmentosa reticularis · DPR

Data availability: 14 ClinVar variants · 3 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 › diffuse palmoplantar keratoderma › dermatopathia pigmentosa reticularis

Related subtypes (31): autosomal dominant palmoplantar keratoderma and congenital alopecia, Clouston syndrome, epidermolytic palmoplantar keratoderma, 1, palmoplantar keratoderma-deafness syndrome, palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome, keratosis palmaris et plantaris-clinodactyly syndrome, Bart-Pumphrey syndrome, Naegeli-Franceschetti-Jadassohn syndrome, palmoplantar keratoderma-sclerodactyly syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, Schöpf-Schulz-Passarge syndrome, hereditary palmoplantar keratoderma, Gamborg-Nielsen type, Papillon-Lefevre disease, Haim-Munk syndrome, mal de Meleda, odonto-onycho-dermal dysplasia, palmoplantar keratoderma, Bothnian type, diffuse nonepidermolytic palmoplantar keratoderma, loricrin keratoderma, skin fragility-woolly hair-palmoplantar keratoderma syndrome, Curly hair - acral keratoderma - caries syndrome, CEDNIK syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, palmoplantar keratoderma, Nagashima type, erythrokeratodermia variabilis, diffuse palmoplantar keratoderma with painful fissures, KID syndrome, diffuse palmoplantar keratoderma - acrocyanosis syndrome, hearing loss with skin disease

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

14 retrieved; paginated sample, class counts are floors:

4 benign, 4 likely pathogenic, 2 uncertain significance, 2 benign/likely benign, 1 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14613	NM_000526.5(KRT14):c.374G>A (p.Arg125His)	KRT14	Pathogenic	criteria provided, multiple submitters, no conflicts
66341	NM_000526.5(KRT14):c.355A>G (p.Met119Val)	KRT14	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1685364	NM_000526.5(KRT14):c.372C>A (p.Asp124Glu)	KRT14	Likely pathogenic	criteria provided, single submitter
1685365	NM_000526.5(KRT14):c.356T>G (p.Met119Arg)	KRT14	Likely pathogenic	criteria provided, single submitter
419836	NM_000526.5(KRT14):c.1163G>A (p.Arg388His)	KRT14	Likely pathogenic	criteria provided, multiple submitters, no conflicts
66369	NM_000526.5(KRT14):c.526-2A>C	KRT14	Likely pathogenic	criteria provided, multiple submitters, no conflicts
14626	NM_000526.5(KRT14):c.54C>A (p.Cys18Ter)	KRT14	Uncertain significance	criteria provided, single submitter
2352985	NM_000526.5(KRT14):c.139G>A (p.Gly47Arg)	KRT14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1668287	NM_000526.5(KRT14):c.188G>A (p.Cys63Tyr)	KRT14	Benign	criteria provided, multiple submitters, no conflicts
66319	NM_000526.5(KRT14):c.1237G>A (p.Ala413Thr)	KRT14	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
66331	NM_000526.5(KRT14):c.189C>T (p.Cys63=)	KRT14	Benign	criteria provided, multiple submitters, no conflicts
66332	NM_000526.5(KRT14):c.193C>T (p.Leu65=)	KRT14	Benign	criteria provided, multiple submitters, no conflicts
66346	NM_000526.5(KRT14):c.369T>C (p.Asn123=)	KRT14	Benign	criteria provided, multiple submitters, no conflicts
781859	NM_000526.5(KRT14):c.166C>T (p.Arg56Cys)	KRT14	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 25 · Orphanet: 7 · 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
KRT14	Strong	Autosomal dominant	dermatopathia pigmentosa reticularis	25

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KRT14	Orphanet:69087	Naegeli-Franceschetti-Jadassohn syndrome
KRT14	Orphanet:79396	Autosomal dominant generalized epidermolysis bullosa simplex, severe form
KRT14	Orphanet:79397	Epidermolysis bullosa simplex with mottled pigmentation
KRT14	Orphanet:79399	Autosomal dominant generalized epidermolysis bullosa simplex, intermediate form
KRT14	Orphanet:79400	Localized epidermolysis bullosa simplex
KRT14	Orphanet:86920	Dermatopathia pigmentosa reticularis
KRT14	Orphanet:89838	Autosomal recessive generalized epidermolysis bullosa simplex

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
KRT14	HGNC:6416	ENSG00000186847	P02533	Keratin, type I cytoskeletal 14	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KRT14	Keratin, type I cytoskeletal 14	The nonhelical tail domain is involved in promoting KRT5-KRT14 filaments to self-organize into large bundles and enhances the mechanical properties involved in resilience of keratin intermediate filaments in vitro.

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)
KRT14	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
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KRT14	193	broad	marker	gingiva, gingival epithelium, upper arm skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRT14	3,351

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRT14	P02533	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Type I hemidesmosome assembly	1	1038.2×	0.008	KRT14
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	543.8×	0.008	KRT14
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	1	278.5×	0.010	KRT14
Developmental Cell Lineages	1	223.9×	0.010	KRT14
Cell junction organization	1	187.2×	0.010	KRT14
Cell-Cell communication	1	137.6×	0.011	KRT14
Formation of the cornified envelope	1	87.8×	0.015	KRT14
Keratinization	1	55.7×	0.020	KRT14
Developmental Biology	1	14.5×	0.069	KRT14

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
intermediate filament bundle assembly	1	2808.7×	0.003	KRT14
response to radiation	1	1203.7×	0.003	KRT14
hair cycle	1	936.2×	0.003	KRT14
morphogenesis of an epithelium	1	343.9×	0.005	KRT14
stem cell differentiation	1	300.9×	0.005	KRT14
keratinocyte differentiation	1	247.8×	0.005	KRT14
intermediate filament organization	1	240.7×	0.005	KRT14
epidermis development	1	210.7×	0.005	KRT14

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
KRT14	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	KRT14

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)
KRT14	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.