Actinic keratosis

Summary

Actinic keratosis (MONDO:0005173) is a disease with 127 GWAS associations across 11 studies and 196 clinical trials. Top therapeutic interventions include ingenol mebutate, imiquimod, and fluorouracil. A subtype of pre-malignant neoplasm — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• GWAS associations: 127
• Clinical trials: 196

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	actinic keratosis
Mondo ID	MONDO:0005173
EFO	EFO:0002496
MeSH	D055623
DOID	DOID:8866
ICD-10-CM	L57.0
ICD-11	1803982621
NCIT	C3148
SNOMED CT	201101007
UMLS	C0022602
MedGen	9627
Is cancer (heuristic)	no

Also known as: actinic (solar) keratosis · actinic keratosis · actinic keratosis (disease) · solar keratosis

Data availability: 127 GWAS associations (11 studies) · 1 HPO phenotype · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › pre-malignant neoplasm › actinic keratosis

Genetics & variants

GWAS landscape

127 GWAS associations across 11 studies. Top hits map to 24 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr16:89645437	1e-323		G	0.22
rs12203592	1e-323	IRF4	C	0.45
rs1805007	4e-319	MC1R	C	0.42
rs16891982	2e-311	SLC45A2	C	0.6
rs6059655	1e-218	RALY	A	0.27
rs1126809	4e-171	TYR	G	0.15
rs62211989	7e-125	TPM3P2 - PIGPP3	G	0.28
rs12913832	3e-107	HERC2	A	0.13
rs12350739	1e-95	BNC2 - RN7SL720P	G	0.11
rs4268748	2e-61	DEF8	C	1.25
rs6791479	1e-40	TPRG1 - TP63	T	0.07
rs1426654	8e-37	SLC24A5	A	0.45
chr8:116610180	6e-34		T	0.06
chr3:188102104	1e-33		G	0.08
chr3:71527191	5e-33		T	0.06
chr13:113543884	3e-32		C	0.06
chr6:31285537	8e-32		T	0.07
rs117744081	3e-28	CPVL	A	0.16
chr6:90958231	6e-26		C	0.05
rs2425025	7e-25	MMP24OS, MMP24	G	1.27
rs12126004	2e-23	CTXND2 - SETDB1	T	0.05
rs2737206	3e-23	TRPS1	T	0.06
rs72928978	6e-23	TPCN2	G	0.07
chr1:204486205	1e-22		G	0.05
rs11571818	3e-22	BRCA2	T	0.24
rs7742789	8e-22	ZNF318 - ABCC10	C	0.05
rs11611584	1e-20	KRT6A - KRT5	C	0.08
rs117132860	1e-20	AHR	G	0.2
rs6007506	1e-20	KIAA0930	C	0.05
rs9549317	4e-20	ATP11A	A	0.06

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90476204	Verma A	2024	97,501	314,618	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90095184	Kim Y	2022	21,462	70,778	Genome-wide association study of actinic keratosis identifies new susceptibility loci implicated in pigmentation and immune regulation pathways.
GCST90129628	Kim Y	2022	16,352	46,758	Genome-wide association study of actinic keratosis identifies new susceptibility loci implicated in pigmentation and immune regulation pathways.
GCST90080354	Backman JD	2021	3,010	384,062	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084340	Backman JD	2021	3,010	384,062	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90436621	Zhou W	2018	2,594	403,439	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90476203	Verma A	2024	2,177	55,636	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90044525	Jiang L	2021	2,033	454,315	A generalized linear mixed model association tool for biobank-scale data.
GCST90480468	Verma A	2024	246	120,611	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90482354	Verma A	2024	246	120,611	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	6
Tier 2: splice/UTR	2
Tier 3: regulatory	2
Tier 4: intronic/intergenic	40

MAF distribution

Bucket	Variants
common (>=0.05)	44
low_freq (0.01-0.05)	5
rare (<0.01)	1
unknown	0

Functional consequences

Consequence	Count
intron_variant	19
unknown	17
missense_variant	6
intergenic_variant	4
TF_binding_site_variant	1
splice_polypyrimidine_tract_variant	1
regulatory_region_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr16:89645437				0.285			1e-323	Tier 4: intronic/intergenic
rs12203592	6	396321	C>G,T	0.16	intron_variant	IRF4	1e-323	Tier 4: intronic/intergenic
rs1805007	16	89919709	C>A,G,T	0.063	missense_variant	MC1R	4e-319	Tier 1: coding
rs16891982	5	33951588	C>A,G	0.038	missense_variant	SLC45A2	2e-311	Tier 1: coding
rs6059655	20	34077942	A>G	0.092	intron_variant	RALY	1e-218	Tier 4: intronic/intergenic
rs1126809	11	89284793	G>A	0.283	missense_variant	TYR	4e-171	Tier 1: coding
rs62211989	20	33950585	G>C	0.058	intergenic_variant	TPM3P2 - PIGPP3	7e-125	Tier 4: intronic/intergenic
rs12913832	15	28120472	A>C,G	0.241	intron_variant	HERC2	3e-107	Tier 4: intronic/intergenic
rs12350739	9	16885019	G>A,C,T	0.435	TF_binding_site_variant	BNC2 - RN7SL720P	1e-95	Tier 3: regulatory
rs4268748	16	89960104	T>C	0.05	intron_variant	DEF8	2e-61	Tier 4: intronic/intergenic
rs6791479	3	189487243	T>A,C	0.431	intergenic_variant	TPRG1 - TP63	1e-40	Tier 4: intronic/intergenic
rs1426654	15	48134287	A>C,G,T	0.201	missense_variant	SLC24A5	8e-37	Tier 1: coding
chr8:116610180				0.447			6e-34	Tier 4: intronic/intergenic
chr3:188102104				0.359			1e-33	Tier 4: intronic/intergenic
chr3:71527191				0.472			5e-33	Tier 4: intronic/intergenic
chr13:113543884				0.499			3e-32	Tier 4: intronic/intergenic
chr6:31285537				0.388			8e-32	Tier 4: intronic/intergenic
rs117744081	7	29092663	A>G	0.032	missense_variant	CPVL	3e-28	Tier 1: coding
chr6:90958231				0.451			6e-26	Tier 4: intronic/intergenic
rs2425025	20	35259351	G>A	0.05	intron_variant	MMP24OS, MMP24	7e-25	Tier 4: intronic/intergenic
rs12126004	1	150917401	T>A,C	0.468	intron_variant	CTXND2 - SETDB1	2e-23	Tier 4: intronic/intergenic
rs2737206	8	115599675	T>A,C,G	0.386	intron_variant	TRPS1	3e-23	Tier 4: intronic/intergenic
rs72928978	11	69063896	G>A	0.117	missense_variant	TPCN2	6e-23	Tier 1: coding
chr1:204486205				0.317			1e-22	Tier 4: intronic/intergenic
rs11571818	13	32394673	T>A,C	0.009	splice_polypyrimidine_tract_variant	BRCA2	3e-22	Tier 2: splice/UTR
rs7742789	6	43378065	C>T	0.305	intron_variant	ZNF318 - ABCC10	8e-22	Tier 4: intronic/intergenic
rs11611584	12	52512251	C>A	0.086	intron_variant	KRT6A - KRT5	1e-20	Tier 4: intronic/intergenic
rs117132860	7	17095084	G>A,C,T	0.019	intron_variant	AHR	1e-20	Tier 4: intronic/intergenic
rs6007506	22	45226133	C>A,T	0.344	intron_variant	KIAA0930	1e-20	Tier 4: intronic/intergenic
rs9549317	13	112881428	A>C,G	0.444	intron_variant	ATP11A	4e-20	Tier 4: intronic/intergenic

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

Drugs indicated for this disease

5 approved, 5 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Diclofenac	Approved (phase 4)
Fluorouracil	Approved (phase 4)
Imiquimod	Approved (phase 4)
Ingenol Mebutate	Approved (phase 4)
Tirbanibulin	Approved (phase 4)
Aminolevulinic Acid	Phase 3 (in late-stage trials)
Ingenol Disoxate	Phase 3 (in late-stage trials)
Methyl Aminolevulinate	Phase 3 (in late-stage trials)
Nitrogen	Phase 3 (in late-stage trials)
Salicylic Acid	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Benzoyl Peroxide, Calcipotriene, Cholecalciferol, Digoxin, Furosemide, Isotretinoin, Melatonin, Paclitaxel, Petrolatum, Tretinoin.

Clinical trials & evidence

Clinical trials

Clinical trials: 196.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	53
PHASE2	41
Not specified	41
PHASE1	26
PHASE4	23
PHASE1/PHASE2	7
EARLY_PHASE1	3
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00110682	PHASE4	COMPLETED	Study of Imiquimod 5% Cream in Addition to Cryotherapy in the Management of Actinic Keratoses
NCT00695578	PHASE4	COMPLETED	Clinical Trial to Evaluate Biafine Cream Versus Standard Care in Subjects With Actinic Keratosis Post Cryotherapy
NCT00696488	PHASE4	COMPLETED	Measuring Adherence To Topical 5-Fluorouracil in a Clinic Population
NCT00777127	PHASE4	COMPLETED	Long-term Effects of Imiquimod and Diclofenac in Actinic Keratoses
NCT01000636	PHASE4	COMPLETED	Gene Expression in Renal Transplant Patients With Field Actinic Keratosis Undergoing Metvix® Photodynamic Therapy (PDT)
NCT01203878	PHASE4	TERMINATED	Treatment of Actinic Keratoses of the Face With Imiquimod 3.75% Cream Followed by Photodynamic Therapy
NCT01229319	PHASE4	UNKNOWN	Imiquimod 3.75% Cream in Combination With Cryotherapy in the Treatment of Hypertrophic Actinic Keratoses
NCT01413763	PHASE4	UNKNOWN	Potential Effect of Topical Imiquimod on Atrial Ectopy in Patients With Actinic Keratosis
NCT01453179	PHASE4	COMPLETED	Long-term Effects of Imiquimod and Diclofenac in Actinic Keratoses (LEIDA 2)
NCT01656226	PHASE4	UNKNOWN	Long Term Efficacy and Safety of Eryfotona AK-NMSC® in Patients With Actinic Keratosis
NCT01926496	PHASE4	COMPLETED	Risk of Squamous Cell Carcinoma on Skin Areas Treated With Ingenol Mebutate Gel, 0.015% and Imiquimod Cream, 5%
NCT02406014	PHASE4	COMPLETED	Efficacy and Safety of Ingenol Mebutate Gel 0.015% Compared to Diclofenac Sodium Gel 3% in Subjects With Actinic Keratoses on the Face or Scalp
NCT02446223	PHASE4	COMPLETED	Evaluate the Efficacy and Safety of Large-Scale Field-Directed Topical Therapy of Actinic Keratosis of the Chest w/Ingenol Mebutate 0.015%
NCT02464709	PHASE4	COMPLETED	Daylight PDT for Actinic Keratoses: a Multicentre Study Comparing Two Photosensitizers (BF-200 ALA Versus MAL)
NCT02647151	PHASE4	UNKNOWN	Efficacy and Safety of Treatment of Actinic Keratoses With Photodynamic Therapy Between MAL Cream and ALA Gel
NCT02716714	PHASE4	COMPLETED	Clinical Trial of Ingenol Mebutate Gel 0.015% & 0.05% in Actinic Keratosis
NCT02866695	PHASE4	COMPLETED	Safety and Efficacy of Ingenol Mebutate Gel 0.015% for Treatment of AK on the Face in Solid Organ Transplant Recipients
NCT02984072	PHASE4	COMPLETED	Menthol for PDT Pain Relief
NCT02990221	PHASE4	COMPLETED	Efficacy of Ingenol Mebutate on Actinic Keratoses and Field Cancerization vs Cryotherapy
NCT03327831	PHASE4	COMPLETED	Study of Daylight Photodynamic Therapy With Aminolevulinic Acid for Actinic Keratoses
NCT03731988	PHASE4	COMPLETED	Efficacy of Ablative Fractional Laser-assisted Photodynamic Therapy According to the Laser Density for Actinic Keratosis
NCT05741294	PHASE4	COMPLETED	A Study of Tirbanibulin on the Wellbeing of Participants With Actinic Keratoses
NCT05900258	PHASE4	COMPLETED	Tirbanibulin 1% Ointment for the Treatment of Chronically Sun-damaged Skin on the Face
NCT07144345	PHASE3	RECRUITING	Study of Reformulated Levulan Kerastick Plus PDT for Actinic Keratosis on Face and Scalp
NCT07144852	PHASE3	RECRUITING	Study of Reformulated Levulan Kerastick Plus PDT for Actinic Keratosis on Upper Extremities
NCT00294320	PHASE3	COMPLETED	Evaluation of Two Different Non-invasive Techniques to Monitor the Clearance of Actinic Keratosis Lesions
NCT00304239	PHASE3	COMPLETED	Metvix PDT Versus Vehicle PDT With Aktilite CL128 Lamp in Patients With Actinic Keratosis on the Face and Scalp
NCT00306800	PHASE3	COMPLETED	Metvix PDT Versus Vehicle PDT With Aktilite CL128 Lamp in Patients With Actinic Keratosis on the Face and Scalp
NCT00308854	PHASE3	COMPLETED	Photodynamic Therapy With PD P 506 A Compared With Placebo-PDT for the Treatment of AK
NCT00308867	PHASE3	COMPLETED	PD P 506 A-PDT Versus Placebo-PDT and Cryosurgery for the Treatment of AK
NCT00472459	PHASE3	COMPLETED	Photodynamic Therapy (PDT) With Metvix® 160 Milligrams/Gram Cream in Organ Transplant Participants With Non-melanoma Skin Cancer
NCT00603798	PHASE3	COMPLETED	Safety and Effectiveness Study of Imiquimod Creams for the Treatment of Actinic Keratoses (AKs)
NCT00859105	PHASE3	COMPLETED	A Randomized, Double-Blind, Parallel-Group, Vehicle-Controlled Therapeutic Equivalence Study of Three Imiquimod Cream 5% Treatments for Patients With Actinic Keratosis
NCT00894647	PHASE3	COMPLETED	Safety and Effectiveness Study of Actinic Keratosis Treatment Following Cryosurgery
NCT00915551	PHASE3	COMPLETED	A Multi-Center Study to Evaluate the Efficacy and Safety of PEP005 (Ingenol Mebutate) Gel, When Used to Treat Actinic Keratoses on the Head (Face or Scalp)
NCT00916006	PHASE3	COMPLETED	A Multi-center Study to Evaluate the Efficacy and Safety of PEP005 (Ingenol Mebutate) Gel, When Used to Treat Actinic Keratoses on the Head (Face or Scalp)
NCT00917306	PHASE3	COMPLETED	A Multi-center Study to Evaluate the Safety and Efficacy of PEP005 (Ingenol Mebutate) Gel, When Used to Treat Actinic Keratoses on Non-head Locations (Trunk and Extremities)
NCT00926952	PHASE3	COMPLETED	Short Incubation Methylaminolevulinate Photodynamic Therapy Without Occlusion
NCT00987246	PHASE3	COMPLETED	Study on the Efficacy of LAS41005 in the Treatment of Actinic Keratosis
NCT01260987	PHASE2/PHASE3	COMPLETED	Fractional CO2 Laser Assisted Photodynamic Therapy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
INGENOL MEBUTATE	4	16
IMIQUIMOD	4	11
FLUOROURACIL	4	10
DICLOFENAC	4	7
AMINOLEVULINIC ACID	4	6
IMIPRAMINE	4	4
METHYL AMINOLEVULINATE	4	4
CALCIPOTRIENE	4	2
PRILOCAINE	4	2
TIRBANIBULIN	4	2
ISOTRETINOIN	4	1
MENTHOL	4	1
NIACINAMIDE	4	1
SALICYLIC ACID	4	1
TRETINOIN	4	1
INGENOL DISOXATE	3	4
ALANINE	3	2
INGENOL	3	1
LEVOMENTHOL	3	1
BIMIRALISIB	2	1
RESIQUIMOD	2	1
VEHICLE	0	3
CHEMBL4854670	0	2
CHEMBL4532249	0	1
CHEMBL4563773	0	1
CHEMBL4796961	0	1