Erythrokeratodermia variabilis et progressiva 5

disease

On this page

Also known as EKVP5

Summary

Erythrokeratodermia variabilis et progressiva 5 (MONDO:0033015) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	erythrokeratodermia variabilis et progressiva 5
Mondo ID	MONDO:0033015
OMIM	617756
DOID	DOID:0080251
UMLS	C4540331
MedGen	1626376
GARD	0018669
Is cancer (heuristic)	no

Also known as: EKVP5

Data availability: 5 ClinVar variants · 1 GenCC gene-disease record.

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 › erythrokeratodermia variabilis › erythrokeratodermia variabilis et progressiva 5

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

5 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
3891539	NM_002282.3(KRT83):c.72_78del (p.Pro25fs)	KRT83	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
446111	NM_002282.3(KRT83):c.811del (p.Ser271fs)	KRT83	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3116740	NM_002282.3(KRT83):c.1361C>T (p.Thr454Met)	KRT83	Uncertain significance	criteria provided, multiple submitters, no conflicts
3891538	NM_002282.3(KRT83):c.1167C>A (p.Cys389Ter)	KRT83	Uncertain significance	criteria provided, single submitter
309520	NM_002282.3(KRT83):c.760A>G (p.Ile254Val)	KRT83	Benign/Likely 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
KRT83	Supportive	Autosomal dominant	erythrokeratodermia variabilis	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KRT83	Orphanet:316	Progressive symmetric erythrokeratodermia
KRT83	Orphanet:573	Monilethrix

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
KRT83	HGNC:6460	ENSG00000170523	P78385	Keratin, type II cuticular Hb3	gencc,clinvar

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)
KRT83	Other/Unknown	no		Keratin_II, Growth_fac_rcpt_cys_sf, IF_conserved

Expression context

Cohort genes with no expression data: 0.

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
diaphragm	1
male germ line stem cell (sensu Vertebrata) in testis	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KRT83	73	tissue_specific	yes	diaphragm, type B pancreatic cell, 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
KRT83	1,053

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KRT83	P78385	74.81

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	KRT83
Keratinization	1	55.7×	0.027	KRT83
Developmental Biology	1	14.5×	0.069	KRT83

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
hair cycle	1	936.2×	0.004	KRT83
intermediate filament organization	1	240.7×	0.005	KRT83
keratinization	1	234.1×	0.005	KRT83
epidermis development	1	210.7×	0.005	KRT83

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
KRT83	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
KRT83	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	KRT83

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)
KRT83	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: KRT83