{
  "version": "0.1.0",
  "reviewed": "2026-09-22",
  "scope": "Selected human, feline, canine and fruit-fly evidence for generation research. Not a complete gene catalogue or a validated genotype-to-appearance predictor.",
  "sources": [
    {"id":"visser2012","title":"Visser et al. (2012) — HERC2 regulation of OCA2","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3290780/","type":"Primary research"},
    {"id":"praetorius2013","title":"Praetorius et al. (2013) — IRF4 and tyrosinase","url":"https://doi.org/10.1016/j.cell.2013.10.022","type":"Primary research"},
    {"id":"eye-color","title":"MedlinePlus Genetics — Eye color","url":"https://medlineplus.gov/genetics/understanding/traits/eyecolor/","type":"NIH reference"},
    {"id":"oca2","title":"MedlinePlus Genetics — OCA2","url":"https://medlineplus.gov/genetics/gene/oca2/","type":"NIH reference"},
    {"id":"tyr","title":"MedlinePlus Genetics — TYR","url":"https://medlineplus.gov/genetics/gene/tyr/","type":"NIH reference"},
    {"id":"mitf","title":"MedlinePlus Genetics — MITF","url":"https://medlineplus.gov/genetics/gene/mitf/","type":"NIH reference"},
    {"id":"pax6","title":"MedlinePlus Genetics — PAX6","url":"https://medlineplus.gov/genetics/gene/pax6/","type":"NIH reference"},
    {"id":"six3","title":"MedlinePlus Genetics — SIX3","url":"https://medlineplus.gov/genetics/gene/six3/","type":"NIH reference"},
    {"id":"anatomy","title":"InformedHealth / NCBI Bookshelf — How does the eye work?","url":"https://www.ncbi.nlm.nih.gov/books/NBK279248/","type":"Anatomy reference"},
    {"id":"pupils2015","title":"Banks et al. (2015) — Animal pupil shapes","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4643806/","type":"Primary research"},
    {"id":"cat-kit2014","title":"David et al. (2014) — KIT, white coat and blue iris in cats","url":"https://pubmed.ncbi.nlm.nih.gov/25085922/","type":"Primary research"},
    {"id":"cat-pax32024","title":"Different Founding Effects Underlie Dominant Blue Eyes in the Domestic Cat (2024)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11240321/","type":"Primary research"},
    {"id":"dog-alx42018","title":"Deane-Coe et al. (2018) — A duplication associated with blue eyes in dogs","url":"https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007648","type":"Primary research"},
    {"id":"ey1995","title":"Halder et al. (1995) — eyeless and Drosophila eye development","url":"https://pubmed.ncbi.nlm.nih.gov/7892602/","type":"Primary research"}
  ],
  "genes": [
    {"symbol":"HERC2","category":"Pigmentation","species":"Homo sapiens","role":"A regulatory region inside HERC2 can influence transcription of the nearby OCA2 gene.","variant":"rs12913832","evidence":"In the studied human melanocytes, the T allele supported stronger enhancer–promoter contact and higher OCA2 expression than C. These are the paper’s T/C allele labels.","context":"Human epidermal melanocytes and cellular reporter assays; Visser et al., 2012.","appearance":"Relevant to iris pigmentation. The rendered color is an illustrative choice, not a predicted color for a person.","mapping":"Illustrated in Eye Lab","limits":"One regulatory example cannot predict the combined effect of a person’s variants. T/C notation here must not be mixed with A/G reports without strand conversion.","sources":["visser2012","eye-color"]},
    {"symbol":"OCA2","category":"Pigmentation","species":"Homo sapiens","role":"Encodes a melanosomal protein involved in pigmentation.","variant":null,"evidence":"OCA2 supports melanin production. Its expression is influenced by regulatory elements, including the studied HERC2 region.","context":"Human pigmentation; NIH gene reference and HERC2/OCA2 study.","appearance":"Pigment quantity contributes to iris appearance, alongside tissue structure and other genes.","mapping":"Pathway context","limits":"This generator does not convert an OCA2 expression measurement or variant into a calibrated amount of iris pigment.","sources":["oca2","visser2012"]},
    {"symbol":"IRF4","category":"Pigmentation","species":"Homo sapiens","role":"A transcription factor involved in a melanocyte regulatory pathway that influences TYR.","variant":"rs12203592","evidence":"The T allele reduces enhancer activity and IRF4 expression in the studied pigmentation pathway; IRF4 cooperates with MITF to regulate TYR.","context":"Human pigmentation association and experimental melanocyte work; Praetorius et al., 2013.","appearance":"Relevant to pigmentation. The example illustrates the direction of a mechanism, not a quantitative eye-color outcome.","mapping":"Illustrated in Eye Lab","limits":"No combined HERC2 + IRF4 prediction is implemented. Effects depend on tissue and genetic context.","sources":["praetorius2013","eye-color"]},
    {"symbol":"TYR","category":"Pigmentation","species":"Homo sapiens","role":"Encodes tyrosinase, an enzyme used in early steps of melanin production.","variant":null,"evidence":"Tyrosinase activity is necessary for normal melanin synthesis.","context":"Human gene reference; IRF4/MITF pathway research.","appearance":"Pigment synthesis affects eye, skin and hair pigmentation.","mapping":"Reference only","limits":"Variants can have health effects beyond color. No specific TYR variant is simulated.","sources":["tyr","praetorius2013"]},
    {"symbol":"MITF","category":"Pigmentation","species":"Homo sapiens","role":"A transcription factor involved in pigment-cell development and function, including melanin pathways.","variant":null,"evidence":"MITF regulates other genes in pigment cells and has roles in the retinal pigment epithelium.","context":"Human gene reference and pigmentation studies.","appearance":"Provides a regulatory connection between cell identity and pigmentation.","mapping":"Reference only","limits":"MITF is not an independent iris-pattern or color dial. No variant or dosage is mapped to mesh parameters.","sources":["mitf","visser2012","praetorius2013"]},
    {"symbol":"PAX6","category":"Development","species":"Homo sapiens","role":"A transcription factor required for aspects of eye development, with roles in other organs too.","variant":null,"evidence":"Disrupted PAX6 function can affect the iris and multiple other eye structures.","context":"Human developmental genetics; NIH gene reference.","appearance":"Relevant to how eye structures develop, rather than only their surface color.","mapping":"Reference only","limits":"A PAX6 slider would imply an unsupported shape prediction. The generator does not model embryonic development or pathogenic variants.","sources":["pax6"]},
    {"symbol":"SIX3","category":"Development","species":"Homo sapiens","role":"A transcription factor involved in early forebrain and eye development.","variant":null,"evidence":"SIX3 helps regulate developmental programs involved in structures including the lens and retina.","context":"Human developmental genetics; NIH gene reference.","appearance":"Relevant to formation of the eye and surrounding developmental context.","mapping":"Reference only","limits":"Changing a developmental regulator is not equivalent to safely selecting a finished eye shape. No SIX3 variant is simulated.","sources":["six3"]},
    {"symbol":"KIT","category":"Pigmentation","species":"Felis catus","role":"A gene involved in melanocyte biology; regulatory-region insertions are associated with dominant white and white spotting in domestic cats.","variant":"FERV1 insertions at the W locus","evidence":"The studied KIT insertion states were associated with dominant white/blue iris or white spotting, depending on the insertion.","context":"Cat pedigrees and a survey of 270 cats from 30 breeds; David et al., 2014.","appearance":"One documented context relevant to a blue cat iris; used as a cited conceptual basis for low-pigment cat concepts.","mapping":"Cited concept","limits":"Not all blue cat eyes have this cause. The generator does not infer a KIT genotype or calculate iris color from expression. Associated traits extend beyond the eye.","sources":["cat-kit2014"]},
    {"symbol":"PAX3","category":"Pigmentation","species":"Felis catus","role":"A developmental regulator linked to melanoblast biology and some dominant-blue-eye lineages in cats.","variant":"A reported intronic retroviral insertion in an Altai-related lineage","evidence":"A 2024 study proposed a PAX3 regulatory-region insertion as an allele underlying a specific dominant-blue-eye lineage.","context":"Selected domestic-cat lineages; this is not a general explanation for every blue-eyed cat.","appearance":"An alternative source-backed concept for blue feline irises.","mapping":"Cited concept","limits":"A reported candidate mechanism is not a measured expression-to-color formula. No inference of genotype from the generated image is made.","sources":["cat-pax32024"]},
    {"symbol":"ALX4","category":"Pigmentation","species":"Canis lupus familiaris","role":"A developmental gene near a duplication associated with blue eyes and heterochromia in dogs.","variant":"98.6-kb duplication near ALX4","evidence":"A 2018 study found a strong association. Altered ALX4 regulation was proposed as a mechanism, requiring further functional investigation.","context":"Canine association study; includes Siberian huskies and other dogs.","appearance":"A cited conceptual basis for a blue canine iris.","mapping":"Cited concept","limits":"Association and a proposed regulatory explanation are kept distinct from experimentally measured gene-expression effects.","sources":["dog-alx42018"]},
    {"symbol":"ey","category":"Development","species":"Drosophila melanogaster","role":"eyeless encodes a Pax6-related transcription factor in fruit-fly eye development.","variant":null,"evidence":"Experimental work established a role in initiating eye-development programs in the studied fly context.","context":"Drosophila developmental research; Halder et al., 1995.","appearance":"Developmental context for compound-eye concepts; exterior facet count remains an artistic parameter.","mapping":"Reference only","limits":"This does not supply a rule for generating functional eyes in arbitrary body locations or species. No experimental intervention is specified.","sources":["ey1995"]}
  ],
  "anatomy": [
    {"part":"Sclera","description":"The outer supporting coat of the eyeball. Modeled as a curved shell with an anterior opening.","source":"anatomy"},
    {"part":"Iris","description":"The colored tissue surrounding the pupil. Modeled with radial structure, a collarette and pigment variation.","source":"anatomy"},
    {"part":"Pupil","description":"An opening in the iris. Dilation is a physiological state; the size control is not a gene-expression measurement.","source":"anatomy"},
    {"part":"Cornea","description":"The transparent front surface. Modeled as a separate curved layer; the preview is not an optical simulation of vision.","source":"anatomy"}
  ]
}