Lichen planopilaris

Summary

Lichen planopilaris (MONDO:0018879) is a disease with 1 cohort gene and 11 clinical trials. Top therapeutic interventions include cravacitinib, ixekizumab, and mechlorethamine.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 15
• Clinical trials: 11

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		300	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0000962	Hyperkeratosis	Very frequent (80-99%)
HP:0001596	Alopecia	Very frequent (80-99%)
HP:0100725	Lichenification	Very frequent (80-99%)
HP:0200034	Papule	Very frequent (80-99%)
HP:0000989	Pruritus	Frequent (30-79%)
HP:0001231	Abnormal fingernail morphology	Frequent (30-79%)
HP:0004334	Dermal atrophy	Frequent (30-79%)
HP:0200042	Skin ulcer	Frequent (30-79%)
HP:0001053	Hypopigmented skin patches	Occasional (5-29%)
HP:0001059	Pterygium	Occasional (5-29%)
HP:0001806	Onycholysis	Occasional (5-29%)
HP:0002242	Abnormal intestine morphology	Occasional (5-29%)
HP:0008066	Abnormal blistering of the skin	Occasional (5-29%)
HP:0012115	Hepatitis	Occasional (5-29%)
HP:0100649	Neoplasm of the oral cavity	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	lichen planopilaris
Mondo ID	MONDO:0018879
MeSH	C535892
Orphanet	525
ICD-10-CM	L66.1
ICD-11	572258139
SNOMED CT	64540004
UMLS	C0023645
MedGen	44150
GARD	0003247
Is cancer (heuristic)	no

Also known as: follicular lichen planus · frontal fibrosing alopecia (subtype) · Kossard disease · lichen follicularis · lichen planopilaris classic type · lichen planus follicularis · LPP

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › disorder of pilosebaceous unit › hair anomaly › alopecia › lichen planopilaris

Related subtypes (25): alopecia, isolated, telogen effluvium, alopecia areata, chemotherapy-induced alopecia, alopecia mucinosa, atrichia with papular lesions, loose anagen syndrome, Satoyoshi syndrome, alopecia-intellectual disability-hypergonadotropic hypogonadism syndrome, hereditary hypotrichosis with recurrent skin vesicles, alopecia antibody deficiency, pseudopelade of Brocq, frontal fibrosing alopecia, Quinquaud’s folliculitis decalvans, Graham Little-Piccardi-Lassueur syndrome, hypotrichosis simplex, alopecia totalis, hypotrichosis simplex of the scalp, endocrine alopecia, alopecia universalis onychodystrophy vitiligo, central centrifugal cicatricial alopecia, ectodermal dysplasia alopecia preaxial polydactyly, Slti-Salem syndrome, microcephaly sparse hair intellectual disability seizures, alopecia universalis

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
1690306	NM_001098672.2(HEPHL1):c.3280C>T (p.Arg1094Ter)	HEPHL1	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
HEPHL1	HGNC:30477	ENSG00000181333	Q6MZM0	Ferroxidase HEPHL1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HEPHL1	Ferroxidase HEPHL1	Is a copper-binding glycoprotein with ferroxidase activity.

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)
HEPHL1	Other/Unknown	no		Cu_oxidase_Cu_BS, Cupredoxin, Cu-oxidase_C

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
esophagus mucosa	1
male germ line stem cell (sensu Vertebrata) in testis	1
tonsil	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HEPHL1	60	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, esophagus mucosa, tonsil

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HEPHL1	1,673

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HEPHL1	Q6MZM0	89.76

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
copper ion transport	1	1685.2×	0.001	HEPHL1
intracellular iron ion homeostasis	1	244.2×	0.004	HEPHL1

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
HEPHL1	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	HEPHL1

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)
HEPHL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	4
Not specified	4
EARLY_PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07532603	PHASE2/PHASE3	RECRUITING	A Phase 2/3 Study of Brepocitinib in Adults With Lichen Planopilaris
NCT07487948	PHASE2	RECRUITING	Safety and Biomarker Responses of Delgocitinib (JAK1,2,3/TYK2 Inhibitor) in Central Centrifugal Cicatricial Alopecia and Lichen Planopilaris
NCT03417141	PHASE2	COMPLETED	Valchlor in the Treatment of Lichen Planopilaris
NCT04409041	PHASE2	COMPLETED	Oral Low-Dose Naltrexone for Lichen Planopilaris and Frontal Fibrosing Alopecia
NCT06091956	PHASE2	COMPLETED	A Study of Deucravacitinib to Treat LPP and FFA
NCT03346668	EARLY_PHASE1	COMPLETED	Role of Neurogenic Inflammation and Topical 6% Gabapentin Therapy in Symptomatic Scarring Alopecia
NCT05030415	EARLY_PHASE1	COMPLETED	Ixekizumab in Adult Patients With Lichen Planus and Lichen Planopilaris
NCT06512753	Not specified	RECRUITING	The Effectiveness of Hydroxychloroquine Versus Methotrexate in the Treatment of Lichen Planopilaris in Routine Clinical Care: a Patient Preference Trial
NCT00691769	Not specified	COMPLETED	Expression of Fas Protein in Skin Biopsies of Participants With Scarring Alopecia
NCT03082560	Not specified	UNKNOWN	Design and Validation of a New Assessment Tool for Lichen Planopilaris
NCT06512766	Not specified	COMPLETED	a Retrospective Study on the Systemic Treatment of LPP and FFA

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CRAVACITINIB	4	3
IXEKIZUMAB	4	1
MECHLORETHAMINE	4	1
NALTREXONE	4	1
BREPOCITINIB	3	1
DELGOCITINIB	3	1
CHEMBL4747591	0	1
CHEMBL5421204	0	1