Keratosis pilaris atrophicans

Summary

Keratosis pilaris atrophicans (MONDO:0018855) is a disease with 1 cohort gene and 8 clinical trials.

At a glance

• Cohort genes: 1
• ClinVar variants: 7
• Clinical trials: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	keratosis pilaris atrophicans
Mondo ID	MONDO:0018855
MeSH	C537412
OMIM	604093
Orphanet	498
DOID	DOID:0080751
ICD-11	273325594
SNOMED CT	400059005
UMLS	C0263428
MedGen	75520
GARD	0018694
Is cancer (heuristic)	no

Also known as: amelogenesis imperfecta, hypoplastic-hypomaturation, X-linked 2 · Atrophodermia reticulata · Atrophodermia reticulata symmetrica faciei · Atrophodermia vermiculata · burnett Schwartz Berberian syndrome · folliculitis ulerythematosa · folliculitis ulerythematosa reticulata · honeycomb atrophy · keratosis pilaris · keratosis pilaris atrophicans · keratosis pilaris atrophicans facies · KPA · ulerythema ophryogenes · ulerythema ophryogenes with multiple congenital anomalies · ulerythema ophryogenesis

Data availability: 7 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › epidermal disease › keratosis pilaris atrophicans

Related subtypes (24): porokeratosis, Darier disease, absence of fingerprints-congenital milia syndrome, hyperkeratosis lenticularis perstans, keratolytic winter erythema, Hailey-Hailey disease, VPS13A-related neurodegenerative disease, acanthosis nigricans-insulin resistance-muscle cramps-acral enlargement syndrome, keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome, seborrhea-like dermatitis with psoriasiform elements, psoriasis 14, pustular, palmoplantar pustulosis, hereditary poikiloderma, congenital erosive and vesicular dermatosis, neonatal inflammatory skin and bowel disease, 13q12.3 microdeletion syndrome, zinc-responsive necrolytic acral erythema, ichthyosis, erythrokeratoderma, hereditary palmoplantar keratoderma, inherited epidermolysis bullosa, punctate acrokeratoderma freckle-like pigmentation, aquagenic palmoplantar keratoderma, phrynoderma

Subtypes (4): keratosis follicularis spinulosa decalvans, atrophoderma vermiculata, ulerythema ophryogenesis, keratosis pilaris atrophicans faciei

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

7 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
930178	NM_002332.3(LRP1):c.300C>T (p.Asp100=)	LRP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2433514	NM_002332.3(LRP1):c.8999A>G (p.His3000Arg)	LRP1	Uncertain significance	criteria provided, single submitter
2433515	NM_002332.3(LRP1):c.7896C>A (p.Asp2632Glu)	LRP1	Uncertain significance	criteria provided, single submitter
3575004	NM_002332.3(LRP1):c.1284G>A (p.Ser428=)	LRP1	Uncertain significance	criteria provided, single submitter
3891589	NM_002332.3(LRP1):c.1214T>C (p.Ile405Thr)	LRP1	Uncertain significance	criteria provided, single submitter
3891590	NM_002332.3(LRP1):c.506G>A (p.Gly169Asp)	LRP1	Uncertain significance	criteria provided, single submitter
4813295	NM_002332.3(LRP1):c.9845A>G (p.His3282Arg)	LRP1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
LRP1	Moderate	Autosomal recessive	keratosis pilaris atrophicans	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LRP1	Orphanet:2340	Keratosis follicularis spinulosa decalvans
LRP1	Orphanet:79100	Atrophoderma vermiculata

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
LRP1	HGNC:6692	ENSG00000123384	Q07954	Prolow-density lipoprotein receptor-related protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LRP1	Prolow-density lipoprotein receptor-related protein 1	Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells.

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)
LRP1	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF

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
ascending aorta	1
descending thoracic aorta	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRP1	293	ubiquitous	marker	stromal cell of endometrium, descending thoracic aorta, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LRP1	2,662

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LRP1	Q07954	7

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
Scavenging of heme from plasma	1	878.5×	0.007	LRP1
Binding and Uptake of Ligands by Scavenger Receptors	1	543.8×	0.007	LRP1
Metabolism of fat-soluble vitamins	1	380.7×	0.007	LRP1
Visual phototransduction	1	259.6×	0.007	LRP1
Retinoid metabolism and transport	1	248.3×	0.007	LRP1
Metabolism of vitamins and cofactors	1	116.5×	0.013	LRP1
Sensory Perception	1	95.2×	0.014	LRP1
Vesicle-mediated transport	1	34.8×	0.032	LRP1
Metabolism	1	11.6×	0.086	LRP1

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
positive regulation of transcytosis	1	16852.0×	0.001	LRP1
positive regulation of lipid transport	1	8426.0×	0.001	LRP1
positive regulation of reverse cholesterol transport	1	8426.0×	0.001	LRP1
astrocyte activation involved in immune response	1	4213.0×	0.001	LRP1
negative regulation of platelet-derived growth factor receptor-beta signaling pathway	1	4213.0×	0.001	LRP1
regulation of extracellular matrix disassembly	1	3370.4×	0.001	LRP1
positive regulation of lysosomal protein catabolic process	1	3370.4×	0.001	LRP1
amyloid-beta clearance by transcytosis	1	2407.4×	0.002	LRP1
amyloid-beta clearance by cellular catabolic process	1	2106.5×	0.002	LRP1
positive regulation of amyloid-beta clearance	1	2106.5×	0.002	LRP1
regulation of extracellular matrix organization	1	1872.4×	0.002	LRP1
transcytosis	1	1685.2×	0.002	LRP1
negative regulation of smooth muscle cell migration	1	1532.0×	0.002	LRP1
enzyme-linked receptor protein signaling pathway	1	1296.3×	0.002	LRP1
lipoprotein transport	1	991.3×	0.002	LRP1
amyloid-beta clearance	1	936.2×	0.002	LRP1
aorta morphogenesis	1	887.0×	0.002	LRP1
apoptotic cell clearance	1	887.0×	0.002	LRP1
positive regulation of endocytosis	1	802.5×	0.002	LRP1
lysosomal transport	1	702.2×	0.002	LRP1
positive regulation of cholesterol efflux	1	624.1×	0.002	LRP1
negative regulation of SMAD protein signal transduction	1	601.9×	0.002	LRP1
retinoid metabolic process	1	495.6×	0.003	LRP1
cellular response to amyloid-beta	1	391.9×	0.004	LRP1
negative regulation of Wnt signaling pathway	1	343.9×	0.004	LRP1
receptor internalization	1	324.1×	0.004	LRP1
positive regulation of protein localization to plasma membrane	1	271.8×	0.004	LRP1
phagocytosis	1	240.7×	0.005	LRP1
receptor-mediated endocytosis	1	221.7×	0.005	LRP1
transport across blood-brain barrier	1	179.3×	0.006	LRP1

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
LRP1	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	LRP1

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)
LRP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 8.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6
PHASE4	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00944216	PHASE4	TERMINATED	Efficacy and Safety of Salkera Emollient Foam in the Treatment of Moderate to Severe Keratosis Pilaris, a Prospective Study
NCT04797663	PHASE4	COMPLETED	Long-pulsed 1064 nm Nd-YAG Laser Versus TCA 20% in Treatment of Keratosis Pilaris
NCT07078461	Not specified	RECRUITING	Investigating the Safety and Efficacy of the 1927-nm Thulium Laser in Keratosis Pilaris
NCT01281644	Not specified	COMPLETED	Treatment of Keratosis Pilaris With 810 nm Diode Laser
NCT03243617	Not specified	COMPLETED	Cosmetic Study of AO+Mist in Improving the Appearance of Skin Afflicted With Keratosis Pilaris
NCT05535517	Not specified	UNKNOWN	Development and Validation of an Investigator Global Assessment Score for Keratosis Pilaris
NCT05666011	Not specified	UNKNOWN	Laser to Aid in Treatment of Keratosis Pilaris on Arms
NCT06032078	Not specified	UNKNOWN	Evaluation of the Responsiveness of Investigator Global Assessment Score for Keratosis Pilaris