| domain | entity/finding | evidence-ready interpretation | suggested ontology IDs/terms |
|---|---|---|---|
| disease identifier | Porokeratosis | Heterogeneous group of keratinization disorders defined histologically by the cornoid lamella; evidence is aggregated from disease-level reviews plus primary variant-specific studies (pqac-00000019, pqac-00000020, pqac-00000004) | MONDO: verify exact class; MeSH: Porokeratosis; ICD-10: verify specific coding used locally |
| synonym/nomenclature | Porokeratoses | Preferred umbrella term when referring to the disease spectrum rather than a single clinicopathologic variant (pqac-00000019, pqac-00000014) | MeSH term mapping to Porokeratosis; disease synonym: porokeratoses |
| variant | Disseminated superficial actinic porokeratosis (DSAP) | Most common clinical variant in reviewed series; multiple small annular atrophic/keratotic macules-papules on sun-exposed skin, often adult onset, female-predominant in reviews (pqac-00000004, pqac-00000018, pqac-00000020) | HPO: Actinic keratosis-like lesion; Abnormality of the skin; Multiple skin lesions; UBERON: skin of upper limb, skin of lower limb |
| variant | Disseminated superficial porokeratosis (DSP) | Disseminated non-actinic form, often childhood onset, involving sun-exposed and non-exposed areas (pqac-00000018, pqac-00000020) | HPO: Generalized skin lesions; Childhood onset; UBERON: trunk skin |
| variant | Porokeratosis of Mibelli (PM) | Often begins in childhood; enlarging annular plaques with raised keratotic border, commonly limbs/trunk; higher malignant potential than DSAP (pqac-00000005, pqac-00000018, pqac-00000020) | HPO: Plaque; Hyperkeratotic papule; Childhood onset; UBERON: limb skin |
| variant | Linear porokeratosis (LP) | Usually congenital/early onset, linear or Blaschkoid distribution; among the highest malignant-transformation risks in reviews (pqac-00000017, pqac-00000018, pqac-00000021) | HPO: Linear skin lesion; Blaschkoid distribution; Congenital onset |
| variant | Verrucous porokeratosis / porokeratosis ptychotropica | Pruritic or burning verrucous plaques, often anogenital/intertriginous, diagnostically difficult, prolonged course (pqac-00000000, pqac-00000006) | HPO: Pruritus; Burning sensation; Verrucous lesion; UBERON: perianal skin, genital skin |
| variant | Punctate palmoplantar porokeratosis / PPPD spectrum | Punctate keratotic lesions of palms/soles; low but non-zero premalignant concern in reviews (pqac-00000017, pqac-00000021) | HPO: Palmoplantar hyperkeratosis; Punctate keratosis; UBERON: skin of palm, skin of sole |
| variant | Porokeratoma | Solitary well-demarcated porokeratotic plaque/nodule, usually sporadic; PMVK implicated in a minority of studied index cases (pqac-00000001, pqac-00000016) | HPO: Solitary skin nodule; Hyperkeratotic plaque |
| gene | MVK | Core causal gene in porokeratosis spectrum; mevalonate-pathway enzyme; AD inheritance with incomplete penetrance in familial disease; implicated strongly in DSAP and other variants (pqac-00000014, pqac-00000012, pqac-00000013) | HGNC: MVK; GO: mevalonate pathway, cholesterol biosynthetic process |
| gene | PMVK | Core causal gene; loss-of-function variants reported in AD porokeratosis; also found in sporadic porokeratoma subset (pqac-00000011, pqac-00000012, pqac-00000016) | HGNC: PMVK; GO: phosphomevalonate kinase activity, isoprenoid biosynthetic process |
| gene | MVD | Core causal gene in porokeratosis; part of mevalonate/isoprenoid biosynthesis and implicated in second-hit models (pqac-00000012, pqac-00000022) | HGNC: MVD; GO: diphosphomevalonate decarboxylase activity |
| gene | FDPS | Core causal gene in porokeratosis reviews; supports mevalonate-pathway disease model (pqac-00000014, pqac-00000024) | HGNC: FDPS; GO: farnesyl diphosphate biosynthetic process |
| gene, emerging | FDFT1 | Emerging 2024 mechanism: gene-specific somatic epigenetic mosaicism reported for a non-hereditary localized form; important but should be labeled emerging until independently consolidated across cohorts (pqac-00000014) | HGNC: FDFT1; label as emerging/candidate mechanistic gene |
| gene, candidate/emerging | SLC17A9 | Candidate/legacy DSAP-associated gene/locus in some pedigrees; not part of the canonical mevalonate-pathway core and should be labeled candidate/emerging (pqac-00000012, pqac-00000019) | HGNC: SLC17A9; label as candidate susceptibility/causal gene pending broader consensus |
| inheritance | Autosomal dominant with incomplete penetrance | Best-supported familial inheritance pattern across common inherited forms; one review cites ~22% penetrance for DSAP (pqac-00000014, pqac-00000019, pqac-00000020) | HP: Autosomal dominant inheritance; HP: Reduced penetrance |
| molecular mechanism | Mevalonate/isoprenoid pathway dysfunction | Unifying current model: deficiency of enzymes in cholesterol/isoprenoid biosynthesis perturbs keratinocyte differentiation, apoptosis control, and local epidermal homeostasis (pqac-00000014, pqac-00000013, pqac-00000024) | GO: cholesterol biosynthetic process; isoprenoid biosynthetic process; regulation of keratinocyte differentiation |
| molecular mechanism | Second-hit / mosaic clonal expansion | Localized lesions can reflect postzygotic or somatic second-hit events driving clonal lesional epidermis over a germline background (pqac-00000022, pqac-00000019) | GO: somatic mutation; clonal cell proliferation |
| molecular mechanism | Premature keratinocyte apoptosis beneath cornoid lamella | Classic downstream histopathologic process with granular layer loss and abnormal terminal differentiation (pqac-00000020, pqac-00000022) | GO: apoptotic process; keratinocyte differentiation; epidermis development |
| cell/anatomy | Keratinocyte | Principal implicated cell type in pathogenesis and malignant transformation models (pqac-00000019, pqac-00000020, pqac-00000022) | CL: keratinocyte |
| cell/anatomy | Epidermis / spinous-granular layers | Primary tissue compartment showing cornoid lamella, granular layer attenuation, dyskeratosis, and abnormal keratinization (pqac-00000005, pqac-00000006, pqac-00000020) | UBERON: epidermis; GO CC: cornified envelope |
| phenotype | Annular keratotic plaque/papule with raised rim | Core clinical morphology across variants (pqac-00000004, pqac-00000018, pqac-00000020) | HPO: Annular skin lesion; Hyperkeratotic papule; Plaque |
| phenotype | Atrophic center | Common central lesional feature, especially in DSAP and PM-type lesions (pqac-00000004, pqac-00000016) | HPO: Cutaneous atrophy |
| phenotype | Pruritus | Common but variable symptom; up to one-third in DSAP review data and prominent in ptychotropic/verrucous forms (pqac-00000018, pqac-00000000) | HPO: Pruritus |
| phenotype | Burning sensation | Reported particularly in verrucous/ptychotropic disease (pqac-00000000) | HPO: Burning sensation |
| phenotype | Symmetric photo-distributed lesions | Characteristic DSAP distribution on extensor extremities and back/shoulders (pqac-00000004, pqac-00000018, pqac-00000020) | HPO: Photosensitivity-related skin finding; UBERON: skin of upper limb, skin of lower limb, back skin |
| diagnostic hallmark | Cornoid lamella | Histopathologic hallmark and defining diagnostic feature of porokeratosis spectrum (pqac-00000004, pqac-00000019, pqac-00000020) | SNOMED/pathology concept: cornoid lamella; GO/UBERON not directly applicable |
| diagnostic method | Dermoscopy | Often shows a peripheral keratotic rim corresponding to the cornoid lamella; helpful for clinical diagnosis and monitoring suspicious change (pqac-00000004, pqac-00000005, pqac-00000022) | NCIT: Dermoscopy |
| trigger/risk factor | Ultraviolet radiation / sun exposure | Major trigger and exacerbating factor, especially for DSAP; seasonal worsening and predilection for sun-exposed sites support gene-environment interaction (pqac-00000004, pqac-00000019, pqac-00000020) | CHEBI/Exposome: ultraviolet radiation exposure |
| trigger/risk factor | Immunosuppression | Important acquired trigger/risk state, including organ transplantation and immunosuppressive therapy (pqac-00000017, pqac-00000020, pqac-00000005) | NCIT: Immunosuppression |
| trigger/risk factor | Mechanical trauma / friction / scratching | Reported aggravating factors, especially in intertriginous/verrucous forms (pqac-00000000, pqac-00000017, pqac-00000020) | Exposome term: skin trauma; friction exposure |
| trigger/risk factor | Medication-associated porokeratosis | Reported with several drugs in review literature; evidence is largely case-based (pqac-00000020) | NCIT: Drug exposure |
| trigger/risk factor | Infection-associated cases | Case-level associations reported for HPV, HSV, HCV, leishmania; causality uncertain (pqac-00000020) | NCBI Taxonomy terms as appropriate; label as reported trigger association |
| cancer complication | Keratinocyte carcinoma, especially squamous cell carcinoma | Main serious complication; overall malignant transformation estimated about 6.8-11.6% in one review, with higher risk in LP and PM than DSAP (pqac-00000003, pqac-00000017, pqac-00000020) | NCIT: Squamous Cell Carcinoma of the Skin; Basal Cell Carcinoma |
| prognostic factor | Large, long-standing, non-sun-exposed or acral lesions; older age; prior irradiation; immunosuppression | Factors associated with increased malignant risk in reviews (pqac-00000003, pqac-00000020) | NCIT: Risk factor |
| intervention | Topical lovastatin plus cholesterol | Pathogenesis-directed therapy based on mevalonate-pathway defect; studied prospectively in DSAP and now a principal modern intervention of interest (pqac-00000010, pqac-00000007, pqac-00000008) | NCIT: Lovastatin; CHEBI: cholesterol; NCIT: Topical Cream Dosage Form |
| intervention | Topical lovastatin monotherapy | Randomized DSAP trial suggests benefit may not require added cholesterol in all patients, though comparative evidence is still limited (pqac-00000008, pqac-00000010) | NCIT: Lovastatin |
| intervention | Surgical excision / shave-curettage | Best suited to localized lesions and suspicious or transformed lesions; several case-based reports show good local control (pqac-00000003, pqac-00000023) | NCIT: Surgical Excision; Curettage |
| intervention | Cryotherapy | Common local destructive therapy with variable efficacy and recurrence risk (pqac-00000006, pqac-00000023) | NCIT: Cryotherapy |
| intervention | Topical 5-fluorouracil | Traditional topical option; some complete responses reported but evidence mainly case based (pqac-00000003, pqac-00000023) | NCIT: Fluorouracil |
| intervention | Topical imiquimod | Used especially in PM and some localized variants; response inconsistent (pqac-00000006, pqac-00000023) | NCIT: Imiquimod |
| intervention | Topical/systemic retinoids including acitretin | Frequently used for disseminated or hyperkeratotic disease; outcomes variable and relapse common (pqac-00000003, pqac-00000023) | NCIT: Acitretin; Retinoid Therapy |
| intervention | Photodynamic therapy / laser-based treatments | Employed in DSAP and localized lesions with modest or variable response and procedure-related adverse effects (pqac-00000011, pqac-00000023) | NCIT: Photodynamic Therapy; Carbon Dioxide Laser Therapy |
| prevention/surveillance | Sun protection and long-term skin cancer surveillance | Supported by the disease’s photo-triggering and premalignant potential; biopsy is recommended for suspicious change (pqac-00000004, pqac-00000020, pqac-00000023) | NCIT: Sunscreen/Sun Protection Counseling; Skin Examination |
| evidence caveat | Population prevalence/incidence | Robust population-based incidence and prevalence are not well established in retrieved sources; avoid over-precise epidemiologic coding without registry confirmation (pqac-00000019, pqac-00000018) | annotation note: evidence gap |
| evidence caveat | Protective factors | No validated genetic protective factors were identified in the retrieved evidence base (pqac-00000014, pqac-00000019) | annotation note: none established |
| evidence caveat | Model organisms / other species | No disease-faithful animal model or robust natural veterinary counterpart was validated in the retrieved materials; current evidence is mainly human clinical/lesional tissue based (pqac-00000022, pqac-00000019) | annotation note: evidence gap |


*Table: This table summarizes ontology-ready disease, gene, phenotype, mechanism, trigger, complication, and intervention annotations for porokeratosis. It is designed to support knowledge-base population while clearly labeling candidate or emerging findings and evidence gaps.*