Skin sensitivity to sun
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Summary
Skin sensitivity to sun (MONDO:0005434) is a disease with 8 cohort genes (85 GWAS associations across 13 studies).
At a glance
- Cohort genes: 8
- GWAS associations: 85
- ClinVar variants: 3
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | skin sensitivity to sun |
| Mondo ID | MONDO:0005434 |
| EFO | EFO:0004795 |
| UMLS | C0349506 |
| MedGen | 87601 |
| Is cancer (heuristic) | no |
Data availability: 3 ClinVar variants · 85 GWAS associations (13 studies).
Disease family
Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › dermatitis › radiodermatitis › photosensitivity disease › skin sensitivity to sun
Related subtypes (3): photoallergic dermatitis, phototoxic dermatitis, polymorphic light eruption
Genetics & variants
GWAS landscape
85 GWAS associations across 13 studies. Top hits map to 11 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| chr15:27985101 | 1e-192 | T | 2.3 | |
| chr16:89919342 | 2e-163 | CA | 2.72 | |
| rs16891982 | 1e-58 | SLC45A2 | C | 0.58 |
| rs1805007 | 2e-55 | MC1R | T | 2.94 |
| chr16:90040361 | 7e-50 | G | 2.01 | |
| chr16:89154148 | 1e-42 | T | 1.59 | |
| rs35412 | 6e-36 | SLC45A2 | C | 0.54 |
| chr16:89546737 | 1e-28 | T | 1.39 | |
| rs4911414 | 2e-24 | RPS2P1 - ASIP; RPS2P1 - ASIP | G | 1.76 |
| chr16:89669483 | 5e-23 | CTG | 0.64 | |
| rs7713279 | 6e-23 | ADAMTS12 - RXFP3 | G | 0.3 |
| rs12931267 | 8e-23 | FANCA | G | 0.44 |
| rs35406 | 2e-22 | SLC45A2 | G | 0.5 |
| rs12203592 | 8e-20 | IRF4 | T | 0.23 |
| chr16:13934224 | 6e-19 | T | 1.34 | |
| rs13177787 | 1e-18 | ADAMTS12 - RXFP3 | T | 0.34 |
| rs10080040 | 5e-18 | SLC45A2 | T | 0.61 |
| rs11742467 | 5e-17 | ADAMTS12 - RXFP3 | G | 0.27 |
| rs1946267 | 2e-16 | ADAMTS12 - RXFP3 | A | 0.18 |
| rs2278007 | 9e-16 | SLC45A2 | G | 0.45 |
| rs7380538 | 1e-15 | SLC45A2 | A | 0.38 |
| chr16:89775768 | 2e-14 | G | 0.61 | |
| rs12913832 | 4e-14 | HERC2 | G | 0.2 |
| rs1833923 | 2e-13 | ADAMTS12 - RXFP3 | A | 0.19 |
| chr15:27871170 | 4e-13 | A | 3.42 | |
| rs1184030188 | 4e-13 | SLC45A2 | C | 0.53 |
| chr11:89178195 | 5e-13 | T | 2.88 | |
| rs6451047 | 1e-12 | SLC45A2 | T | 0.82 |
| rs2331343 | 2e-12 | ADAMTS12 - RXFP3 | G | 0.36 |
| rs2591719 | 3e-12 | ADAMTS12 | A | 0.34 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST90077603 | Backman JD | 2021 | 173,164 | 249,406 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90081589 | Backman JD | 2021 | 173,164 | 249,406 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90077604 | Backman JD | 2021 | 93,163 | 329,407 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90081590 | Backman JD | 2021 | 93,163 | 329,407 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90077602 | Backman JD | 2021 | 89,584 | 332,986 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90081588 | Backman JD | 2021 | 89,584 | 332,986 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90077605 | Backman JD | 2021 | 75,919 | 346,651 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90081591 | Backman JD | 2021 | 75,919 | 346,651 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90255686 | Farre X | 2023 | 0 | 0 | Skin Phototype and Disease: A Comprehensive Genetic Approach to Pigmentary Traits Pleiotropy Using PRS in the GCAT Cohort. |
| GCST90255687 | Farre X | 2023 | 0 | 0 | Skin Phototype and Disease: A Comprehensive Genetic Approach to Pigmentary Traits Pleiotropy Using PRS in the GCAT Cohort. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|---|
| Tier 1: coding | 3 |
| Tier 2: splice/UTR | 4 |
| Tier 3: regulatory | 1 |
| Tier 4: intronic/intergenic | 42 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 28 |
| low_freq (0.01-0.05) | 11 |
| rare (<0.01) | 9 |
| unknown | 2 |
Functional consequences
| Consequence | Count |
|---|---|
| intron_variant | 18 |
| unknown | 12 |
| intergenic_variant | 11 |
| 3_prime_UTR_variant | 4 |
| missense_variant | 3 |
| intergenic_variant; intergenic_variant | 1 |
| regulatory_region_variant | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| chr15:27985101 | 0.009 | 1e-192 | Tier 4: intronic/intergenic | |||||
| chr16:89919342 | 0.005 | 2e-163 | Tier 4: intronic/intergenic | |||||
| rs16891982 | 5 | 33951588 | C>A,G | 0.15 | missense_variant | SLC45A2 | 1e-58 | Tier 1: coding |
| rs1805007 | 16 | 89919709 | C>A,G,T | 0.06 | missense_variant | MC1R | 2e-55 | Tier 1: coding |
| chr16:90040361 | 0.003 | 7e-50 | Tier 4: intronic/intergenic | |||||
| chr16:89154148 | 0.006 | 1e-42 | Tier 4: intronic/intergenic | |||||
| rs35412 | 5 | 33967040 | C>G,T | 0.103 | intron_variant | SLC45A2 | 6e-36 | Tier 4: intronic/intergenic |
| chr16:89546737 | 0.008 | 1e-28 | Tier 4: intronic/intergenic | |||||
| rs4911414 | 20;20 | 34141638 | T>A,G | 0.08 | intergenic_variant; intergenic_variant | RPS2P1 - ASIP; RPS2P1 - ASIP | 2e-24 | Tier 4: intronic/intergenic |
| chr16:89669483 | 0.005 | 5e-23 | Tier 4: intronic/intergenic | |||||
| rs7713279 | 5 | 33928797 | T>A,G | 0.228 | intergenic_variant | ADAMTS12 - RXFP3 | 6e-23 | Tier 4: intronic/intergenic |
| rs12931267 | 16 | 89752324 | C>G | 0.091 | intron_variant | FANCA | 8e-23 | Tier 4: intronic/intergenic |
| rs35406 | 5 | 33946038 | A>C,G,T | 0.068 | 3_prime_UTR_variant | SLC45A2 | 2e-22 | Tier 2: splice/UTR |
| rs12203592 | 6 | 396321 | C>G,T | 0.141 | intron_variant | IRF4 | 8e-20 | Tier 4: intronic/intergenic |
| chr16:13934224 | 0.007 | 6e-19 | Tier 4: intronic/intergenic | |||||
| rs13177787 | 5 | 33926949 | T>A,C | 0.129 | intergenic_variant | ADAMTS12 - RXFP3 | 1e-18 | Tier 4: intronic/intergenic |
| rs10080040 | 5 | 33950346 | T>A | 0.034 | intron_variant | SLC45A2 | 5e-18 | Tier 4: intronic/intergenic |
| rs11742467 | 5 | 33899585 | G>A | 0.195 | intergenic_variant | ADAMTS12 - RXFP3 | 5e-17 | Tier 4: intronic/intergenic |
| rs1946267 | 5 | 33921705 | A>G,T | 0.197 | intergenic_variant | ADAMTS12 - RXFP3 | 2e-16 | Tier 4: intronic/intergenic |
| rs2278007 | 5 | 33951446 | A>C,G | 0.025 | 3_prime_UTR_variant | SLC45A2 | 9e-16 | Tier 2: splice/UTR |
| rs7380538 | 5 | 33946450 | A>G | 0.034 | 3_prime_UTR_variant | SLC45A2 | 1e-15 | Tier 2: splice/UTR |
| chr16:89775768 | 0.003 | 2e-14 | Tier 4: intronic/intergenic | |||||
| rs12913832 | 15 | 28120472 | A>C,G | 0.358 | intron_variant | HERC2 | 4e-14 | Tier 4: intronic/intergenic |
| rs1833923 | 5 | 33903329 | C>A | 0.476 | intergenic_variant | ADAMTS12 - RXFP3 | 2e-13 | Tier 4: intronic/intergenic |
| chr15:27871170 | 4e-13 | Tier 4: intronic/intergenic | ||||||
| rs1184030188 | 5 | 33966428 | 0.04 | intron_variant | SLC45A2 | 4e-13 | Tier 4: intronic/intergenic | |
| chr11:89178195 | 5e-13 | Tier 4: intronic/intergenic | ||||||
| rs6451047 | 5 | 33956911 | T>A,C,G | 0.015 | intron_variant | SLC45A2 | 1e-12 | Tier 4: intronic/intergenic |
| rs2331343 | 5 | 33921589 | T>C,G | 0.07 | intergenic_variant | ADAMTS12 - RXFP3 | 2e-12 | Tier 4: intronic/intergenic |
| rs2591719 | 5 | 33835538 | G>A,C,T | 0.081 | intron_variant | ADAMTS12 | 3e-12 | Tier 4: intronic/intergenic |
ClinVar germline variants
3 retrieved; paginated sample, class counts are floors:
1 conflicting classifications of pathogenicity; other; risk factor, 1 conflicting classifications of pathogenicity, 1 pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 981245 | NM_001983.4(ERCC1):c.321+61_525+132del | ERCC1 | Pathogenic | no assertion criteria provided |
| 978472 | NM_001983.4(ERCC1):c.466C>T (p.Arg156Trp) | ERCC1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 9 | NM_000410.4(HFE):c.845G>A (p.Cys282Tyr) | HFE | Conflicting classifications of pathogenicity; other; risk factor | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 16 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| TYR | Orphanet:352734 | Minimal pigment oculocutaneous albinism type 1 |
| TYR | Orphanet:352737 | Temperature-sensitive oculocutaneous albinism type 1 |
| TYR | Orphanet:79431 | Oculocutaneous albinism type 1A |
| TYR | Orphanet:79434 | Oculocutaneous albinism type 1B |
| TYR | Orphanet:895 | Waardenburg syndrome type 2 |
| SLC45A2 | Orphanet:79435 | Oculocutaneous albinism type 4 |
| ERCC1 | Orphanet:1466 | COFS syndrome |
| ERCC1 | Orphanet:90322 | Cockayne syndrome type 2 |
| HERC2 | Orphanet:329195 | Developmental delay with autism spectrum disorder and gait instability |
| HFE | Orphanet:443057 | Sporadic porphyria cutanea tarda |
| HFE | Orphanet:443062 | Familial porphyria cutanea tarda |
| HFE | Orphanet:465508 | Symptomatic form of HFE-related hemochromatosis |
| HFE | Orphanet:586 | Cystic fibrosis |
| HFE | Orphanet:648581 | Digenic hemochromatosis |
| MC1R | Orphanet:618 | Familial melanoma |
| MC1R | Orphanet:79432 | Oculocutaneous albinism type 2 |
Cohort genes → proteins
8 cohort genes, 8 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| gwas_only | 6 |
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| TYR | HGNC:12442 | ENSG00000077498 | P14679 | Tyrosinase | gwas |
| RALY | HGNC:15921 | ENSG00000125970 | Q9UKM9 | RNA-binding protein Raly | gwas |
| SLC45A2 | HGNC:16472 | ENSG00000164175 | Q9UMX9 | Membrane-associated transporter protein | gwas |
| ERCC1 | HGNC:3433 | ENSG00000012061 | P07992 | DNA excision repair protein ERCC-1 | clinvar |
| HERC2 | HGNC:4868 | ENSG00000128731 | O95714 | E3 ubiquitin-protein ligase HERC2 | gwas |
| HFE | HGNC:4886 | ENSG00000010704 | Q30201 | Hereditary hemochromatosis protein | clinvar |
| MC1R | HGNC:6929 | ENSG00000258839 | Q01726 | Melanocyte-stimulating hormone receptor | gwas |
| ASIP | HGNC:745 | ENSG00000101440 | P42127 | Agouti-signaling protein | gwas |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| TYR | Tyrosinase | This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. |
| RALY | RNA-binding protein Raly | RNA-binding protein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the liver. |
| SLC45A2 | Membrane-associated transporter protein | Proton-associated glucose and sucrose transporter. |
| ERCC1 | DNA excision repair protein ERCC-1 | Non-catalytic component of a structure-specific DNA repair endonuclease responsible for the 5’-incision during DNA repair. |
| HERC2 | E3 ubiquitin-protein ligase HERC2 | E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. |
| HFE | Hereditary hemochromatosis protein | Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin. |
| MC1R | Melanocyte-stimulating hormone receptor | G protein-coupled receptor that binds melanocyte-stimulating hormones (alpha, beta, and gamma-MSH) and adrenocorticotropic hormone/ACTH, which are peptide products of the POMC precursor protein. |
| ASIP | Agouti-signaling protein | Signaling protein that functions as an antagonist of melanocyte-stimulating-hormone receptor MC1R, thereby playing a role in the regulation of melanogenesis. |
Protein-family classification
Druggable: 4 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.5
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 |
|---|---|---|---|
| Transporter | 1 | 9.7× | 0.578 |
| Antibody/Immunoglobulin | 1 | 3.6× | 0.578 |
| GPCR | 1 | 3.0× | 0.578 |
| Enzyme (other) | 1 | 1.5× | 0.753 |
| Transcription factor | 1 | 1.0× | 0.773 |
| Other/Unknown | 3 | 0.7× | 0.919 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| TYR | Enzyme (other) | yes | 1.14.18.1 | Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin |
| RALY | Other/Unknown | no | RRM_dom, Nucleotide-bd_a/b_plait_sf, hnRNP_C | |
| SLC45A2 | Transporter | yes | MFS, MFS_trans_sf | |
| ERCC1 | Other/Unknown | no | ERCC1/RAD10/SWI10, RuvA_2-like, Restrct_endonuc-II-like | |
| HERC2 | Transcription factor | no | Reg_chr_condens, Znf_ZZ, HECT_dom | |
| HFE | Antibody/Immunoglobulin | yes | MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set | |
| MC1R | GPCR | yes | GPCR_Rhodpsn, MSH_rcpt, Melcrt_ACTH_rcpt | |
| ASIP | Other/Unknown | no | Agouti, Agouti_dom, Agouti_dom_sf |
Expression context
Cohort genes with no expression data: 0.
6 cohort genes 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) | 8 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | 2 |
| pigmented layer of retina | 2 |
| granulocyte | 2 |
| apex of heart | 2 |
| upper leg skin | 1 |
| ganglionic eminence | 1 |
| ventricular zone | 1 |
| primordial germ cell in gonad | 1 |
| parotid gland | 1 |
| right atrium auricular region | 1 |
| cerebellar cortex | 1 |
| right hemisphere of cerebellum | 1 |
| sural nerve | 1 |
| olfactory bulb | 1 |
| stromal cell of endometrium | 1 |
| type B pancreatic cell | 1 |
| left testis | 1 |
| right uterine tube | 1 |
| left ovary | 1 |
| right ovary | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| TYR | 59 | tissue_specific | marker | pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis, upper leg skin |
| RALY | 294 | ubiquitous | marker | ganglionic eminence, granulocyte, ventricular zone |
| SLC45A2 | 100 | tissue_specific | marker | male germ line stem cell (sensu Vertebrata) in testis, pigmented layer of retina, primordial germ cell in gonad |
| ERCC1 | 285 | ubiquitous | marker | apex of heart, parotid gland, right atrium auricular region |
| HERC2 | 146 | marker | sural nerve, right hemisphere of cerebellum, cerebellar cortex | |
| HFE | 238 | ubiquitous | marker | type B pancreatic cell, olfactory bulb, stromal cell of endometrium |
| MC1R | 180 | broad | yes | granulocyte, right uterine tube, left testis |
| ASIP | 158 | tissue_specific | yes | apex of heart, left ovary, right ovary |
Protein interactions among cohort
Intra-cohort edges: 8.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| TYR | 3,663 |
| RALY | 3,651 |
| HERC2 | 2,843 |
| ERCC1 | 2,085 |
| HFE | 1,569 |
| SLC45A2 | 1,295 |
| MC1R | 1,169 |
| ASIP | 473 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| ASIP | MC1R | string_interaction |
| ASIP | RALY | string_interaction |
| ASIP | SLC45A2 | string_interaction |
| ASIP | TYR | string_interaction |
| MC1R | RALY | string_interaction |
| MC1R | SLC45A2 | string_interaction |
| MC1R | TYR | string_interaction |
| SLC45A2 | TYR | string_interaction |
Structural data
PDB: 7 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| HERC2 | O95714 | 15 |
| ERCC1 | P07992 | 14 |
| MC1R | Q01726 | 5 |
| ASIP | P42127 | 4 |
| HFE | Q30201 | 2 |
| TYR | P14679 | 1 |
| RALY | Q9UKM9 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| SLC45A2 | Q9UMX9 | 77.96 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 26. Enrichment computed across 8 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Melanin biosynthesis | 2 | 761.3× | 6e-05 | TYR, SLC45A2 |
| Transferrin endocytosis and recycling | 1 | 61.4× | 0.087 | HFE |
| HDR through Single Strand Annealing (SSA) | 1 | 48.8× | 0.087 | ERCC1 |
| Fanconi Anemia Pathway | 1 | 46.4× | 0.087 | ERCC1 |
| Regulation of MITF-M-dependent genes involved in pigmentation | 1 | 44.3× | 0.087 | TYR |
| Dual Incision in GG-NER | 1 | 43.3× | 0.087 | ERCC1 |
| Formation of Incision Complex in GG-NER | 1 | 42.3× | 0.087 | ERCC1 |
| Transcriptional and post-translational regulation of MITF-M expression and activity | 1 | 29.7× | 0.087 | MC1R |
| Dual incision in TC-NER | 1 | 28.8× | 0.087 | ERCC1 |
| Nonhomologous End-Joining (NHEJ) | 1 | 28.0× | 0.087 | HERC2 |
| SUMOylation of DNA damage response and repair proteins | 1 | 24.4× | 0.087 | HERC2 |
| Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks | 1 | 24.4× | 0.087 | HERC2 |
| G2/M DNA damage checkpoint | 1 | 20.0× | 0.089 | HERC2 |
| Processing of DNA double-strand break ends | 1 | 19.0× | 0.089 | HERC2 |
| MITF-M-regulated melanocyte development | 1 | 19.0× | 0.089 | MC1R |
| Class A/1 (Rhodopsin-like receptors) | 1 | 12.4× | 0.114 | MC1R |
| Peptide ligand-binding receptors | 1 | 12.4× | 0.114 | MC1R |
| G alpha (s) signalling events | 1 | 12.2× | 0.114 | MC1R |
| Metabolism of amino acids and derivatives | 1 | 11.3× | 0.117 | SLC45A2 |
| GPCR ligand binding | 1 | 10.7× | 0.117 | MC1R |
| GPCR downstream signalling | 1 | 7.2× | 0.162 | MC1R |
| Signaling by GPCR | 1 | 6.7× | 0.166 | MC1R |
| Antigen processing: Ubiquitination & Proteasome degradation | 1 | 6.2× | 0.171 | HERC2 |
| Developmental Biology | 1 | 2.4× | 0.379 | MC1R |
| Metabolism | 1 | 1.9× | 0.434 | SLC45A2 |
| Signal Transduction | 1 | 1.7× | 0.463 | MC1R |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| melanin biosynthetic process | 3 | 486.1× | 2e-06 | TYR, MC1R, ASIP |
| melanin biosynthetic process from tyrosine | 2 | 1053.2× | 6e-05 | TYR, SLC45A2 |
| positive regulation of melanin biosynthetic process | 2 | 351.1× | 3e-04 | MC1R, ASIP |
| UV-damage excision repair | 2 | 324.1× | 3e-04 | ERCC1, MC1R |
| UV protection | 2 | 300.9× | 3e-04 | ERCC1, MC1R |
| pigmentation | 2 | 175.5× | 8e-04 | TYR, MC1R |
| negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I | 1 | 2106.5× | 0.006 | HFE |
| eye pigment biosynthetic process | 1 | 1053.2× | 0.010 | TYR |
| regulation of iron ion transport | 1 | 1053.2× | 0.010 | HFE |
| sucrose transport | 1 | 702.2× | 0.010 | SLC45A2 |
| response to iron ion starvation | 1 | 702.2× | 0.010 | HFE |
| pyrimidine dimer repair by nucleotide-excision repair | 1 | 526.6× | 0.010 | ERCC1 |
| obsolete syncytium formation | 1 | 526.6× | 0.010 | ERCC1 |
| telomeric DNA-containing double minutes formation | 1 | 526.6× | 0.010 | ERCC1 |
| positive regulation of t-circle formation | 1 | 526.6× | 0.010 | ERCC1 |
| negative regulation of protection from non-homologous end joining at telomere | 1 | 526.6× | 0.010 | ERCC1 |
| negative regulation of CD8-positive, alpha-beta T cell activation | 1 | 526.6× | 0.010 | HFE |
| response to blue light | 1 | 421.3× | 0.012 | TYR |
| lysosomal lumen pH elevation | 1 | 421.3× | 0.012 | SLC45A2 |
| mitotic recombination | 1 | 351.1× | 0.012 | ERCC1 |
| negative regulation of telomere maintenance | 1 | 351.1× | 0.012 | ERCC1 |
| post-embryonic hemopoiesis | 1 | 351.1× | 0.012 | ERCC1 |
| negative regulation of T cell cytokine production | 1 | 300.9× | 0.012 | HFE |
| negative regulation of melanin biosynthetic process | 1 | 300.9× | 0.012 | ASIP |
| cellular response to iron ion | 1 | 300.9× | 0.012 | HFE |
| positive regulation of feeding behavior | 1 | 300.9× | 0.012 | MC1R |
| cell population proliferation | 2 | 25.7× | 0.012 | TYR, ERCC1 |
| developmental pigmentation | 1 | 263.3× | 0.013 | SLC45A2 |
| epigenetic programming in the zygotic pronuclei | 1 | 234.1× | 0.013 | ASIP |
| visual perception | 2 | 19.9× | 0.013 | TYR, SLC45A2 |
Therapeutics
Drug target analysis
Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 6
Druggability breadth: 3 of 8 evidence-associated genes (38%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| TYR | ASCORBIC ACID |
| MC1R | BREMELANOTIDE |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| TYR | 10 | 4 |
| MC1R | 6 | 4 |
| RALY | 0 | 0 |
| SLC45A2 | 0 | 0 |
| ERCC1 | 0 | 0 |
| HERC2 | 0 | 0 |
| HFE | 0 | 0 |
| ASIP | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| ASCORBIC ACID | 4 | TYR |
| HEXYLRESORCINOL | 4 | TYR |
| HYDROQUINONE | 4 | TYR |
| BREMELANOTIDE | 4 | MC1R |
| SETMELANOTIDE | 4 | MC1R |
| AFAMELANOTIDE | 4 | MC1R |
| CURCUMIN | 3 | TYR |
| RESVERATROL | 3 | TYR |
| QUERCETIN | 3 | TYR |
| BUTYLATED HYDROXYTOLUENE | 2 | TYR |
| LUTEOLIN | 2 | TYR |
| ARBUTIN | 2 | TYR |
| INTERMEDINE | 2 | MC1R |
| PL-8177 | 2 | MC1R |
| KAEMPFEROL | 1 | TYR |
| DERSIMELAGON PHOSPHATE | 1 | MC1R |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| MC1R | 319 | Functional:164, Binding:155 |
| TYR | 211 | Binding:209, ADMET:2 |
| ERCC1 | 28 | Binding:28 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| TYR | 1.14.18.1 | tyrosinase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| TYR | 211 |
| MC1R | 319 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 8; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
16 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.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| ASCORBIC ACID | 4 | TYR |
| HEXYLRESORCINOL | 4 | TYR |
| HYDROQUINONE | 4 | TYR |
| BREMELANOTIDE | 4 | MC1R |
| SETMELANOTIDE | 4 | MC1R |
| AFAMELANOTIDE | 4 | MC1R |
| CURCUMIN | 3 | TYR |
| RESVERATROL | 3 | TYR |
| QUERCETIN | 3 | TYR |
| BUTYLATED HYDROXYTOLUENE | 2 | TYR |
| LUTEOLIN | 2 | TYR |
| ARBUTIN | 2 | TYR |
| INTERMEDINE | 2 | MC1R |
| PL-8177 | 2 | MC1R |
| KAEMPFEROL | 1 | TYR |
| DERSIMELAGON PHOSPHATE | 1 | MC1R |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | TYR, MC1R |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | HFE |
| D | Druggable family + AlphaFold only, no drug | 1 | SLC45A2 |
| E | Difficult family or no structure, no drug | 4 | RALY, ERCC1, HERC2, ASIP |
Undrugged target profiles
6 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| RALY | 0 | MC1R |
| SLC45A2 | 0 | TYR, MC1R |
| ASIP | 0 | MC1R |
| ERCC1 | 28 | — |
| HERC2 | 0 | — |
| HFE | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.