Familial pityriasis rubra pilaris

Summary

Familial pityriasis rubra pilaris (MONDO:0008251) is a disease caused by CARD14 (GenCC Definitive), with 1 cohort gene and 34 clinical trials. Top therapeutic interventions include cravacitinib, sodium chloride, and alefacept.

At a glance

• Prevalence: 1-9 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CARD14 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 14
• Clinical trials: 34

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		48	Worldwide	Validated
Point prevalence	1-9 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

14 HPO clinical features (Orphanet curated; top 14 by frequency):

HPO ID	Term	Frequency
HP:0000982	Palmoplantar keratoderma	Very frequent (80-99%)
HP:0001019	Erythroderma	Very frequent (80-99%)
HP:0007400	Irregular hyperpigmentation	Very frequent (80-99%)
HP:0200034	Papule	Very frequent (80-99%)
HP:0000989	Pruritus	Frequent (30-79%)
HP:0001072	Thickened skin	Frequent (30-79%)
HP:0001597	Abnormality of the nail	Frequent (30-79%)
HP:0008392	Subungual hyperkeratosis	Frequent (30-79%)
HP:0000163	Abnormal oral cavity morphology	Occasional (5-29%)
HP:0000964	Eczematoid dermatitis	Occasional (5-29%)
HP:0002664	Neoplasm	Occasional (5-29%)
HP:0008064	Ichthyosis	Occasional (5-29%)
HP:0100725	Lichenification	Occasional (5-29%)
HP:0200039	Pustule	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	familial pityriasis rubra pilaris
Mondo ID	MONDO:0008251
MeSH	C531784
OMIM	173200
Orphanet	2897
UMLS	C2930842
MedGen	443914
GARD	0024612
MedDRA	10035116
Is cancer (heuristic)	no

Also known as: Devergie’s disease · hereditary pityriasis rubra pilaris · pityriasis rubra pilaris · pityriasis rubra pilaris–familial type · PRP

Data availability: 1 ClinVar variant · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › epidermal disease › erythrokeratoderma › pityriasis rubra pilaris › familial pityriasis rubra pilaris

Related subtypes (2): adult onset pityriasis rubra pilaris, juvenile onset pityriasis rubra pilaris

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1805648	NM_001366385.1(CARD14):c.1790G>T (p.Arg597Leu)	CARD14	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 1 · 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
CARD14	Definitive	Autosomal dominant	familial pityriasis rubra pilaris	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CARD14	Orphanet:2897	Pityriasis rubra pilaris

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
CARD14	HGNC:16446	ENSG00000141527	Q9BXL6	Caspase recruitment domain-containing protein 14	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CARD14	Caspase recruitment domain-containing protein 14	Acts as a scaffolding protein that can activate the inflammatory transcription factor NF-kappa-B and p38/JNK MAP kinase signaling pathways.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CARD14	Scaffold/PPI	no		CARD, PDZ, Guanylate_kin-like_dom

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
lower esophagus mucosa	1
skin of abdomen	1
skin of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CARD14	179	tissue_specific	yes	lower esophagus mucosa, skin of leg, skin of abdomen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CARD14	1,902

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CARD14	Q9BXL6	75.89

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
activation of NF-kappaB-inducing kinase activity	1	1685.2×	0.005	CARD14
regulation of immune response	1	495.6×	0.007	CARD14
tumor necrosis factor-mediated signaling pathway	1	330.4×	0.007	CARD14
positive regulation of protein phosphorylation	1	276.3×	0.007	CARD14
obsolete positive regulation of NF-kappaB transcription factor activity	1	205.5×	0.008	CARD14
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.018	CARD14
negative regulation of apoptotic process	1	34.8×	0.033	CARD14
apoptotic process	1	28.7×	0.035	CARD14

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
CARD14	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	CARD14

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)
CARD14	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 34.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	16
PHASE4	5
PHASE2	4
PHASE1	4
PHASE2/PHASE3	2
PHASE3	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07497620	PHASE4	NOT_YET_RECRUITING	Bimzelx (Bimekizumab) For The Treatment Of Adult Onset PRP
NCT00815633	PHASE4	TERMINATED	A Pilot Study of Alefacept for the Treatment of Pityriasis Rubra Pilaris
NCT04320498	PHASE4	COMPLETED	Short Term Results of Platelet-rich Plasma in the Treatment of Chronic Anal Fissure
NCT04586361	PHASE4	UNKNOWN	Prospective Analysis of Introperative RegenLab PRP and Hyaluronic Acid in Patients With Knee ACL Tear
NCT05827484	PHASE4	COMPLETED	The Effect of Combined Use of Anti-fibrotic Agent With Platelet Rich Plasma on Skeletal Muscle Healing After Acute Injuries
NCT05412381	PHASE3	RECRUITING	PRP in ACLR to Prevent PTOA
NCT03371888	PHASE2/PHASE3	COMPLETED	The Platelet-Rich Plasma in the Therapy of Temporomandibular Disorders
NCT05160441	PHASE3	COMPLETED	Comparing Platelet Rich Plasma and Corticosteroid for Military & Civilian Patients With Glenohumeral Osteoarthritis
NCT06298110	PHASE2/PHASE3	UNKNOWN	The Effect of PRP on Wound Healing in High Risk Patients Undergoing Abdominal Hysterectomy
NCT06444399	PHASE2	RECRUITING	Deucravacitinib (BMS-986165) for Pityriasis Rubra Pilaris
NCT07470359	PHASE2	RECRUITING	Comparison of Functional Outcomes Following Arthroscopic ACL Reconstruction With Peroneus Longus Autograft With and Without Intra-articular Platelet-Rich Plasma Injection.
NCT03485976	PHASE2	COMPLETED	Ixekizumab in the Treatment of Pityriasis Rubra Pilaris (PRP)
NCT03975153	PHASE2	COMPLETED	Guselkumab in the Treatment of Pityriasis Rubra Pilaris (PRP)
NCT06680856	PHASE1/PHASE2	COMPLETED	Allogeneic Platelet Rich Plasma (PRP) to Treat Diabetic Foot Ulcers
NCT03342573	PHASE1	COMPLETED	Cosentyx (Secukinumab) for the Treatment of Adult Onset Pityriasis Rubra Pilaris
NCT04519047	PHASE1	UNKNOWN	IA Injection of Rejoint Gel and PRP in Patients With Unilateral Knee OA
NCT04640662	PHASE1	COMPLETED	The Effects of Platelet-Rich Plasma Versus Prolotherapy On Rotator Cuff Tendinopathy: A Randomized Controlled Trial.
NCT07456215	PHASE1	COMPLETED	The Effect of Platelet Rich Plasma (PRP) Application on Rotator Cuff Tear.
NCT04556825	Not specified	ACTIVE_NOT_RECRUITING	Arthroscopic Treatment Combined With PRP Injection for Refractory Elbow Epicondylitis
NCT05279560	Not specified	ACTIVE_NOT_RECRUITING	Ovarian PRP (Platelet Rich Plasma) Injection for Follicular Activation
NCT06028009	Not specified	ACTIVE_NOT_RECRUITING	PRP Injections for Genitourinary Syndrome of Menopause
NCT06472323	Not specified	RECRUITING	The Efficacy and Safety of Pulsed Radiofrequency Combined With Platelet-rich Plasma for the Trigeminal Neuralgia
NCT07084272	Not specified	NOT_YET_RECRUITING	PRP Yield and Platelet Distribution With EDTA
NCT07589478	Not specified	NOT_YET_RECRUITING	Augmentation of Arthroscopic Rotator Cuff Repair With Reimplantation of Subacromial Bursa Tissue and Platelet-Rich Plasma
NCT03633266	Not specified	UNKNOWN	Anti-VEGF Instead of Intraoperative PRP in Proliferative Diabetic Retinopathy
NCT03830775	Not specified	WITHDRAWN	A Prospective Randomized Double Blinded Controlled Trial of Non-Operative Management of TFCC Injuries
NCT03937765	Not specified	TERMINATED	The Effect of Platelet Rich Plasma on Pain at Skin Graft Donor Sites
NCT03987256	Not specified	UNKNOWN	ECRB Tendinopathy: Needling ± PRP After Failure of Rehabilitation
NCT04765930	Not specified	UNKNOWN	Combined Q-switched Nd:YAG Laser and Platelet Rich Plasma Versus Q- Switched Nd:YAG Laser Alone in Melasma
NCT04811287	Not specified	TERMINATED	PRP as Adjuvant Treatment to CTR for Severe CTS Tunnel Syndrome
NCT04976361	Not specified	COMPLETED	Macular Vessels Density Before and After PRP in Patients With Proliferative Diabetic Retinopathy
NCT05234840	Not specified	COMPLETED	Platelet-Rich Plasma Epidural Injection an Emerging Strategy in Lumbar Disc Herniation
NCT05241964	Not specified	UNKNOWN	Platelet-rich Plasma(PRP) Injection in ED
NCT05944757	Not specified	UNKNOWN	Compare of PRP Autologous Serum and Autologous Serum by Intrastromal Injection in Different Eye Disease Conditions

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CRAVACITINIB	4	3
SODIUM CHLORIDE	4	2
ALEFACEPT	4	1
BIMEKIZUMAB	4	1
GUSELKUMAB	4	1
HYALURONIC ACID	4	1
IXEKIZUMAB	4	1