TYR

Summary

TYR (tyrosinase, HGNC:12442) is a protein-coding gene on chromosome 11q14.3, encoding Tyrosinase (P14679). This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds.

The enzyme encoded by this gene catalyzes the first 2 steps, and at least 1 subsequent step, in the conversion of tyrosine to melanin. The enzyme has both tyrosine hydroxylase and dopa oxidase catalytic activities, and requires copper for function. Mutations in this gene result in oculocutaneous albinism, and nonpathologic polymorphisms result in skin pigmentation variation. The human genome contains a pseudogene similar to the 3’ half of this gene.

Source: NCBI Gene 7299 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oculocutaneous albinism type 1 (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 57
• Clinical variants (ClinVar): 845 total — 133 pathogenic, 114 likely-pathogenic
• Phenotypes (HPO): 43
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000372

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12442
Approved symbol	TYR
Name	tyrosinase
Location	11q14.3
Locus type	gene with protein product
Status	Approved
Aliases	OCAIA, OCA1A, OCA1
Ensembl gene	ENSG00000077498
Ensembl biotype	protein_coding
OMIM	606933
Entrez	7299

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000263321, ENST00000526139, ENST00000528243

RefSeq mRNA: 1 — MANE Select: NM_000372 NM_000372

CCDS: CCDS8284

Canonical transcript exons

ENST00000263321 — 5 exons

Exon	Start	End
ENSE00000842732	89227823	89227970
ENSE00001153836	89295143	89295759
ENSE00002200807	89177875	89178772
ENSE00003505677	89191202	89191418
ENSE00003681170	89284773	89284954

Expression profiles

Bgee: expression breadth broad, 59 present calls, max score 84.83.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 8.0616 / max 1859.9847, expressed in 69 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116160	4.2954	61
116161	3.7662	56

Top tissues by expression

204 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	84.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.03	gold quality
upper leg skin	UBERON:0004262	75.56	gold quality
skin of leg	UBERON:0001511	75.12	gold quality
skin of abdomen	UBERON:0001416	74.26	gold quality
zone of skin	UBERON:0000014	73.96	gold quality
calcaneal tendon	UBERON:0003701	68.10	gold quality
penis	UBERON:0000989	67.27	silver quality
mammalian vulva	UBERON:0000997	66.03	silver quality
buccal mucosa cell	CL:0002336	58.31	gold quality
tendon	UBERON:0000043	57.56	gold quality
lower lobe of lung	UBERON:0008949	54.46	silver quality
eye	UBERON:0000970	51.95	silver quality
descending thoracic aorta	UBERON:0002345	50.81	gold quality
ascending aorta	UBERON:0001496	47.91	gold quality
thoracic aorta	UBERON:0001515	47.91	gold quality
skin of hip	UBERON:0001554	45.66	silver quality
lateral globus pallidus	UBERON:0002476	44.96	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
lower esophagus mucosa	UBERON:0035834	43.07	silver quality
aorta	UBERON:0000947	42.77	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	42.29	gold quality
ganglionic eminence	UBERON:0004023	42.13	gold quality
right coronary artery	UBERON:0001625	41.93	silver quality
oviduct epithelium	UBERON:0004804	41.68	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
biceps brachii	UBERON:0001507	41.25	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	20.21
E-GEOD-135922	yes	8.81
E-ENAD-20	no	1124.40
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BHLHA15, CDH3, CREB1, HNF1A, LEF1, MITF, NEUROD1, OTX2, PAX3, PAX6, PITX2, POU3F2, POU5F1, POU6F2, PPARG, SOX10, SOX9, TBPL1, TCF4, TFE3, TFEB, TP53, USF1

miRNA regulators (miRDB)

21 targeting TYR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-10397-3P	97.78	65.70	601
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-6824-5P	97.41	68.43	583
HSA-MIR-27A-5P	97.01	65.63	528
HSA-MIR-7161-3P	96.79	68.79	798
HSA-MIR-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969
HSA-MIR-3690	96.44	65.18	737
HSA-MIR-571	95.38	66.54	671

Literature-anchored findings (GeneRIF, showing 40)

• induction of retention in the early secretory pathway by abnormal acidification of melanoma cells (PMID:11812790)
• We report a novel missense substitution, R239W(CGG –> TGG) of the tyrosinase gene in a patient with tyrosinase-negative OCA. (PMID:11858948)
• role of P protein and tyrosinase in oculocutaneous albinism (PMID:12028586)
• Data suggest that maintenance of a chronically hyperpigmented phenotype in chronically photoexposed human skin is the result of a stable increase in the number of tyrosinase positive melanocytes at these sites. (PMID:12519123)
• Data reveal DCoH/HNF-1 alpha expression and transcriptional activity in human epidermal melanocytes in vitro and in situ and identified tyrosinase, the key enzyme for pigmentation, as a new transcriptional target. (PMID:12565907)
• We show that TYR has measurable effects on skin pigmentation differences between the west African and west European parental populations (PMID:12579416)
• This melanoma-associated marker was detected in melanoma cell lines. (PMID:12710945)
• no mutations in oculocutaneou albinism (PMID:12727022)
• A candidate gene for pigmentation. (PMID:12817591)
• Antigen-specific T lymphocyte reactivity to MelanA/MART-1 and tyrosinase peptides was not observed ex vivo in our patients, and only one patient demonstrated responses to MelanA/MART-1 and tyrosinase peptides following in vitro re-stimulation. (PMID:12925214)
• These results suggest that phosphorylation of tyrosinase by PKC-beta induces a complex formation between tyrosinase and TRP-1. (PMID:14623273)
• results shows that organellar pH, proteasome activity, and down-regulation of tyrosinase-related protein 1(TYRP1) expression all contribute to the lack of pigmentation in tyrosinase-positive amelanotic melanoma cells (PMID:14634018)
• DNA variations - mutations and polymorphisms - in about 150 patients with Oculocutaneous albinism (PMID:15146472)
• IVS2-10deltt-7t-a was present in 3 out of 18 alleles in three families (16%), P310insC was present in three alleles in three families (16%) and R278X was found in three alleles (16%), and G97V (290 G-T) was found in 1 out of 18 alleles (PMID:15381243)
• Our study reports the distribution of two novel frameshift and a previously reported nonsense mutations in four OCA1 families from the Indian population. (PMID:15635296)
• Data show that oculocutaneous albinism soluble tyrosinase is an endoplasmic reticulum-associated degradation substrate that, unlike other albino tyrosinases, associates with calreticulin and BiP/GRP78, but not calnexin. (PMID:15677452)
• Endothelin-1 increased tyrosinase levels in melanocytes but suppressed enzyme activity. (PMID:15838343)
• fibroblasts in vitro, particularly when deliberately stressed, have the ability to increase dopa oxidase(tyrosinase) activity in melanocytes of the hair, the skin and the eye (PMID:15854130)
• Sequensce databases contribute to demonstrating novel mutations in tyrosinase of albinism in Indians and Japanese. (PMID:15885985)
• glycan-specific oxidoreductase ERp57 was cross-linked to type I membrane glycoprotein tyrosinase when calnexin and calreticulin were associated (PMID:15958486)
• OCA1 in the Tili population is due to the occurrence of a founder mutation in the TYR as indicated by haplotype analysis. Higher prevalence of the mutation in the population group is due to marriage within the same community. (PMID:16056219)
• the tyrosinase autoantigen was immunorecognized with the same molecular pattern by sera from vitiligo and melanoma patients (PMID:16272362)
• demonstrated that these cells possess tyrosinase as well as L-tyrosine hydroxylase (TH) activity and synthesize melanosomes (PMID:16447258)
• Human Placental protein/peptide fraction mediated increase in tyrosinase expression occurred through transcriptional upregulation to stimulate melanogenesis in primary melanocyte. (PMID:16477373)
• a tyrosinase mutation may have a role in type 1A oculocutaneous albinism (case report) (PMID:16517127)
• TYR is not a modifier of the CYP1B1-associated PCG (primary congenital glaucoma) phenotype in the Saudi Arabian population. (PMID:16565383)
• the transmembrane anchor of a protein may crucially, albeit indirectly, control the folding pathway of the ectodomain, as shown with tyrosinase (PMID:16737954)
• Missense mutations in the tyrosinase gene is asociated with oculocutaneous albinism type 1 (PMID:16907708)
• No genetic susceptibility or increased risk attributed to the tyrosinase gene family in Vogt-Koyanagi-Harada disease in Japanese. (PMID:17200659)
• The expression levels of tyrosinase mRNA and protein were also reduced by paeonol. (PMID:17265558)
• tyrosinase has a role in progression of metastatic melanoma (PMID:17496782)
• tyrosinase has a role in progression of melanoma (PMID:17496783)
• tyrosinase and membrane associated transporter protein polymorphisms may have roles in oculocutaneous albinism type 1 and type 4 in the German population (PMID:17516931)
• data show that chloride ion inhibited tyrosinase in a competitive manner (PMID:17718595)
• Anemonin, an active compound of C. crassifolia, inhibits melanin synthesis by inhibiting the transcription of the genes encoding TYR, TRP1, and TRP2. (PMID:17766092)
• analysis of the mammalian tyrosinase active site with loss of function mutations (PMID:17850513)
• Measurement of Melan-A, gp100, MAGE-3, MIA and tyrosinase represents a prognostic factor and a method for early detection of metastasis and treatment response of melanoma patients. (PMID:18181974)
• The absence of evidence for projection abnormalities in human OCA1a carriers contrasts with the previously reported evidence for abnormalities in cat-carriers of tyrosinase-related albinism. (PMID:18296661)
• Most patients with AROA (autosomal recessive ocular albinism) represent phenotypically mild variants of oculocutaneous albinism , well over half of which is OCA1. (PMID:18326704)
• Tyrosinase-, gp100-, or TRP-2-specific CD8(+) T cells could not be identified in the peripheral blood of individuals with vitiligo. (PMID:18337837)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tyr	ENSDARG00000039077
mus_musculus	Tyr	ENSMUSG00000004651
rattus_norvegicus	Tyr	ENSRNOG00000016421
caenorhabditis_elegans		WBGENE00010661

Paralogs (2): DCT (ENSG00000080166), TYRP1 (ENSG00000107165)

Protein

Protein identifiers

Tyrosinase — P14679 (reviewed: P14679)

Alternative names: LB24-AB, Monophenol monooxygenase, SK29-AB, Tumor rejection antigen AB

All UniProt accessions (2): P14679, L8B082

UniProt curated annotations — full annotation on UniProt →

Function. This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reactions leading to melanin production from tyrosine. In addition to hydroxylating tyrosine to DOPA (3,4-dihydroxyphenylalanine), also catalyzes the oxidation of DOPA to DOPA-quinone, and possibly the oxidation of DHI (5,6-dihydroxyindole) to indole-5,6 quinone.

Subunit / interactions. Forms an OPN3-dependent complex with DCT in response to blue light in melanocytes.

Subcellular location. Melanosome membrane. Melanosome.

Post-translational modifications. Glycosylated.

Disease relevance. Albinism, oculocutaneous, 1A (OCA1A) [MIM:203100] An autosomal recessive disorder in which the biosynthesis of melanin pigment is absent in skin, hair, and eyes. It is characterized by complete lack of tyrosinase activity due to production of an inactive enzyme. Patients present with a life-long absence of melanin pigment after birth, and manifest increased sensitivity to ultraviolet radiation with predisposition to skin cancer. Visual anomalies include decreased acuity, nystagmus, strabismus and photophobia. The disease is caused by variants affecting the gene represented in this entry. Albinism, oculocutaneous, 1B (OCA1B) [MIM:606952] An autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in skin, hair, and eyes. It is characterized by partial lack of tyrosinase activity. Patients have white hair at birth that rapidly turns yellow or blond. They manifest the development of minimal-to-moderate amounts of cutaneous and ocular pigment. Some patients may have with white hair in the warmer areas (scalp and axilla) and progressively darker hair in the cooler areas (extremities). This variant phenotype is due to a loss of tyrosinase activity above 35-37 degrees C. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 2 copper ions per subunit.

Induction. Increased expression after UVB irradiation.

Polymorphism. Genetic variants in TYR define the skin/hair/eye pigmentation variation locus 3 (SHEP3) [MIM:601800]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair. Compound heterozygosity for the R402Q polymorphism and a mutant allele of TYR is a common cause of autosomal recessive ocular albinism. The R402Q polymorphism is also found in Waardenburg syndrome type II with ocular albinism in association with a deletion in the MITF gene.

Similarity. Belongs to the tyrosinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P14679-1	1	yes
P14679-2	2

RefSeq proteins (1): NP_000363* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002227	Tyrosinase_Cu-bd	Domain
IPR008922	Di-copper_centre_dom_sf	Homologous_superfamily
IPR050316	Tyrosinase/Hemocyanin	Family

Pfam: PF00264

Enzyme classification (BRENDA):

• EC 1.14.18.1 — tyrosinase (BRENDA: 187 organisms, 724 substrates, 1610 inhibitors, 691 Km, 303 kcat entries)

Substrate kinetics (BRENDA)

153 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-DOPA	0.016–1930	104
CATECHOL	0.01–2250	60
L-TYROSINE	0.014–145	56
4-METHYLCATECHOL	0.1–2000	33
DOPAMINE	0.11–122	23
TYRAMINE	0.0077–9.53	16
P-CRESOL	0.001–130	15
CHLOROGENIC ACID	0.06–129.5	14
D-TYROSINE	1.2–15	14
PYROGALLOL	0.3–3000	12
CAFFEIC ACID	0.037–174.5	11
CATECHIN	0.479–33.7	11
O2	0.015–421	11
4-TERT-BUTYLCATECHOL	0.263–2.8	9
D-DOPA	0.026–28.7	9

Catalyzed reactions (Rhea), 3 shown:

• L-tyrosine + O2 = L-dopaquinone + H2O (RHEA:18117)
• 2 L-dopa + O2 = 2 L-dopaquinone + 2 H2O (RHEA:34287)
• 2 5,6-dihydroxyindole-2-carboxylate + O2 = 2 indole-5,6-quinone-2-carboxylate + 2 H2O (RHEA:68388)

UniProt features (145 total): sequence variant 119, binding site 6, glycosylation site 6, sequence conflict 6, splice variant 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7RK7	X-RAY DIFFRACTION	2.54

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14679-F1	89.79	0.81

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (6): 367; 390; 180; 202; 211; 363

Glycosylation sites (6): 86, 111, 161, 230, 337, 371

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5662702	Melanin biosynthesis
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation

MSigDB gene sets: 251 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, MODULE_52, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, SWEET_KRAS_ONCOGENIC_SIGNATURE, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_THYMUS_DEVELOPMENT, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, MODULE_335, MODULE_16, LHX3_01, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_2NM_UP, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_2_UP

GO Biological Process (11): melanin biosynthetic process from tyrosine (GO:0006583), eye pigment biosynthetic process (GO:0006726), visual perception (GO:0007601), cell population proliferation (GO:0008283), response to UV (GO:0009411), response to blue light (GO:0009637), response to vitamin D (GO:0033280), melanin biosynthetic process (GO:0042438), pigmentation (GO:0043473), thymus development (GO:0048538), response to cAMP (GO:0051591)

GO Molecular Function (8): tyrosinase activity (GO:0004503), copper ion binding (GO:0005507), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), monooxygenase activity (GO:0004497), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872)

GO Cellular Component (7): cytoplasm (GO:0005737), lysosome (GO:0005764), Golgi-associated vesicle (GO:0005798), melanosome membrane (GO:0033162), melanosome (GO:0042470), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
MITF-M-dependent gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
pigment biosynthetic process	2
response to light stimulus	2
response to oxygen-containing compound	2
melanin biosynthetic process	1
eye pigment metabolic process	1
sensory perception of light stimulus	1
cellular process	1
response to vitamin	1
response to lipid	1
melanin metabolic process	1
secondary metabolite biosynthetic process	1
phenol-containing compound biosynthetic process	1
biological_process	1
hematopoietic or lymphoid organ development	1
gland development	1
response to purine-containing compound	1
response to organophosphorus	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, another compound as one donor, and incorporation of one atom of oxygen	1
transition metal ion binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
oxidoreductase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
lytic vacuole	1
cytoplasmic vesicle	1
melanosome	1
chitosome	1
pigment granule membrane	1
pigment granule	1
cytoplasm	1

Protein interactions and networks

STRING

3652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TYR	OCA2	Q04671	984
TYR	MITF	O75030	978
TYR	PMEL	P40967	961
TYR	MC1R	Q01726	959
TYR	SLC45A2	Q9UMX9	947
TYR	MLANA	Q16655	926
TYR	MAGEA3	P43357	875
TYR	SLC24A5	Q71RS6	870
TYR	SOX10	P56693	869
TYR	CTAG1A	P78358	861
TYR	GPR143	P51810	853
TYR	PAX3	P23760	819
TYR	DCT	P40126	797
TYR	TRPM1	Q7Z4N2	783
TYR	ASIP	P42127	782

IntAct

5 interactions, top by confidence:

A	B	Type	Score
GPR143	TYR	psi-mi:“MI:0915”(physical association)	0.520
GPR143	TYR	psi-mi:“MI:0403”(colocalization)	0.520
TYR	GPR143	psi-mi:“MI:2364”(proximity)	0.520

BioGRID (6): TYR (Affinity Capture-MS), TYR (Synthetic Lethality), Edem3 (Affinity Capture-Western), TYR (Affinity Capture-Western), TYR (Proximity Label-MS), SYVN1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1S3ZX38, A0A2G3AC72, B0Y6R2, F9FAJ9, G4N2X9, G4N4J5, G5EB19, O02768, O19183, O61213, O62664, O62698, O62725, O97554, O97598, P05979, P11344, P14679, P22437, P23219, P27607, P35354, P35355, P54834, P55024, P55033, P70682, P79208, Q01603, Q05769, Q2FSF4, Q2QRV3, Q3ATL6, Q4WPX2, Q4WY82, Q5GQ66, Q61419, Q63921, Q6RET3, Q8AVF5

Diamond homologs: B1VTI5, P06845, P07524, P11344, P12031, P14679, P54834, P55022, P55023, P55024, P55026, P55033, Q00234, Q04604, Q08410, Q0MVP0, Q8MIU0, Q9BDE0, O57405, O93505, P07147, P17643, P29812, P40126, P55025, P55027, P55028, Q2VPW6, Q4R1H1, Q8WN57, Q95119, A0A142I737, A0A261GVB1, A0A8J9R8H5, A0A8J9RRY2, B8NM74, H2A0L0, H2A0L1, P12659, P33180

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MITF	“up-regulates quantity by expression”	TYR	“transcriptional regulation”
PRKCB	up-regulates	TYR	phosphorylation

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

845 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	133
Likely pathogenic	114
Uncertain significance	225
Likely benign	202
Benign	13

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027642	NM_000372.5(TYR):c.1056del (p.Gly353_Ile354insTer)	Pathogenic
1066111	NM_000372.5(TYR):c.132T>A (p.Ser44Arg)	Pathogenic
1298523	NM_000372.5(TYR):c.1037-10_1041del	Pathogenic
1299540	NM_000372.5(TYR):c.859dup (p.Ser287fs)	Pathogenic
1323729	NM_000372.5(TYR):c.715C>T (p.Arg239Trp)	Pathogenic
1338375	NM_000372.5(TYR):c.221_222del (p.Val74fs)	Pathogenic
1354013	NM_000372.5(TYR):c.368T>C (p.Ile123Thr)	Pathogenic
1369307	NM_000372.5(TYR):c.706T>C (p.Trp236Arg)	Pathogenic
1379731	NM_000372.5(TYR):c.255T>A (p.Tyr85Ter)	Pathogenic
1390436	NM_000372.5(TYR):c.71G>A (p.Cys24Tyr)	Pathogenic
1392319	NM_000372.5(TYR):c.661G>T (p.Glu221Ter)	Pathogenic
1403532	NC_000011.9:g.(?88960971)(88961158_?)del	Pathogenic
1431974	NM_000372.5(TYR):c.890dup (p.Leu297fs)	Pathogenic
144105	NM_000372.5(TYR):c.551C>G (p.Ser184Ter)	Pathogenic
1447050	NM_000372.5(TYR):c.94G>T (p.Glu32Ter)	Pathogenic
1453014	NM_000372.5(TYR):c.216del (p.Val74fs)	Pathogenic
1454922	NC_000011.9:g.(?89017921)(89018142_?)del	Pathogenic
1454923	NC_000011.9:g.(?88911122)(89018142_?)del	Pathogenic
1456850	NM_000372.5(TYR):c.825_828del (p.Cys276fs)	Pathogenic
1458013	NM_000372.5(TYR):c.1036+2T>G	Pathogenic
1477155	NM_000372.5(TYR):c.1036G>A (p.Gly346Arg)	Pathogenic
1699463	NM_000372.5(TYR):c.1237del (p.Glu413fs)	Pathogenic
1976135	NM_000372.5(TYR):c.841G>T (p.Glu281Ter)	Pathogenic
1996947	NM_000372.5(TYR):c.667C>T (p.Gln223Ter)	Pathogenic
2095363	NM_000372.5(TYR):c.631C>T (p.His211Tyr)	Pathogenic
2108001	NM_000372.5(TYR):c.359G>A (p.Arg120Lys)	Pathogenic
2119989	NM_000372.5(TYR):c.1141_1160del (p.Ala381fs)	Pathogenic
212705	NM_000372.5(TYR):c.580del (p.Ile194fs)	Pathogenic
2137222	NM_000372.5(TYR):c.124G>A (p.Asp42Asn)	Pathogenic
2137224	NM_000372.5(TYR):c.229C>G (p.Arg77Gly)	Pathogenic

SpliceAI

1503 predictions. Top by Δscore:

Variant	Effect	Δscore
11:89227814:A:AG	acceptor_gain	1.0000
11:89284771:A:AG	acceptor_gain	1.0000
11:89284772:G:GA	acceptor_gain	1.0000
11:89284772:GT:G	acceptor_gain	1.0000
11:89284772:GTA:G	acceptor_gain	1.0000
11:89284772:GTAT:G	acceptor_gain	1.0000
11:89178699:A:G	donor_gain	0.9900
11:89191197:TACAG:T	acceptor_gain	0.9900
11:89191198:ACAGA:A	acceptor_gain	0.9900
11:89191201:GATT:G	acceptor_gain	0.9900
11:89227814:AAT:A	acceptor_gain	0.9900
11:89227815:A:G	acceptor_gain	0.9900
11:89227820:CA:C	acceptor_loss	0.9900
11:89227821:A:G	acceptor_loss	0.9900
11:89227821:AG:A	acceptor_gain	0.9900
11:89227822:G:T	acceptor_loss	0.9900
11:89227822:GG:G	acceptor_gain	0.9900
11:89227966:GACAG:G	donor_loss	0.9900
11:89227967:ACAG:A	donor_loss	0.9900
11:89227968:CAG:C	donor_loss	0.9900
11:89227969:AG:A	donor_loss	0.9900
11:89227970:GG:G	donor_loss	0.9900
11:89227971:G:T	donor_loss	0.9900
11:89227972:T:C	donor_loss	0.9900
11:89284767:CTGCA:C	acceptor_gain	0.9900
11:89284768:TGCAG:T	acceptor_gain	0.9900
11:89284769:GCA:G	acceptor_loss	0.9900
11:89284769:GCAG:G	acceptor_gain	0.9900
11:89284770:CAG:C	acceptor_gain	0.9900
11:89284771:A:AT	acceptor_gain	0.9900

AlphaMissense

3516 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:89178665:T:A	W238R	0.997
11:89178665:T:C	W238R	0.997
11:89178313:A:C	R120S	0.996
11:89178313:A:T	R120S	0.996
11:89178667:G:C	W238C	0.996
11:89178667:G:T	W238C	0.996
11:89284786:T:A	W400R	0.996
11:89284786:T:C	W400R	0.996
11:89178312:G:C	R120T	0.995
11:89191277:C:A	R299S	0.995
11:89178572:T:C	F207L	0.994
11:89178574:T:A	F207L	0.994
11:89178574:T:G	F207L	0.994
11:89191397:A:C	S339R	0.994
11:89191399:C:A	S339R	0.994
11:89191399:C:G	S339R	0.994
11:89227942:T:C	F386L	0.994
11:89227944:C:A	F386L	0.994
11:89227944:C:G	F386L	0.994
11:89178588:G:C	R212T	0.993
11:89191413:T:C	L344P	0.993
11:89191418:G:A	G346R	0.993
11:89191418:G:C	G346R	0.993
11:89227934:A:G	D383G	0.993
11:89178191:T:A	W80R	0.992
11:89178191:T:C	W80R	0.992
11:89178193:G:C	W80C	0.992
11:89178193:G:T	W80C	0.992
11:89178581:T:A	W210R	0.992
11:89178581:T:C	W210R	0.992

dbSNP variants (sampled 300 via entrez): RS1000004636 (11:89271054 C>A,T), RS1000033772 (11:89255357 T>C), RS1000050446 (11:89193524 A>G,T), RS1000060781 (11:89214774 C>T), RS1000098918 (11:89294311 G>A), RS1000123176 (11:89209336 G>A,C), RS1000134407 (11:89187138 T>C), RS1000143523 (11:89234782 T>C), RS1000148629 (11:89191311 C>T), RS1000168464 (11:89220561 C>T), RS1000182790 (11:89238243 G>A), RS1000223384 (11:89184010 T>G), RS1000248047 (11:89223970 A>G), RS1000308650 (11:89260964 T>C), RS1000344306 (11:89217915 T>C)

Disease associations

OMIM: gene MIM:606933 | disease phenotypes: MIM:606952, MIM:203100, MIM:614456, MIM:136520, MIM:160700, MIM:310700

GenCC curated gene-disease

Disease	Classification	Inheritance
oculocutaneous albinism type 1A	Definitive	Autosomal recessive
oculocutaneous albinism type 1B	Strong	Autosomal recessive
minimal pigment oculocutaneous albinism type 1	Supportive	Autosomal recessive
temperature-sensitive oculocutaneous albinism type 1	Supportive	Autosomal recessive
Waardenburg syndrome type 2	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
oculocutaneous albinism type 1	Definitive	AR

Mondo (20): oculocutaneous albinism type 1B (MONDO:0011749), oculocutaneous albinism type 1A (MONDO:0008745), oculocutaneous albinism (MONDO:0018910), oculocutaneous albinism type 1 (MONDO:0018135), ocular albinism (MONDO:0017304), albinism (MONDO:0043209), hearing loss disorder (MONDO:0005365), breast cancer (MONDO:0007254), melanoma, cutaneous malignant, susceptibility to, 8 (MONDO:0013759), temperature-sensitive oculocutaneous albinism type 1 (MONDO:0018137), autosomal recessive ocular albinism (MONDO:0040653), foveal hypoplasia (MONDO:0044203), choroidal neovascularization (MONDO:0810000), strabismus (MONDO:0003432), hypopigmentation of the skin (MONDO:0019290)

Orphanet (9): Oculocutaneous albinism type 1 (Orphanet:352731), Temperature-sensitive oculocutaneous albinism type 1 (Orphanet:352737), Oculocutaneous albinism type 1B (Orphanet:79434), Oculocutaneous albinism type 1A (Orphanet:79431), Oculocutaneous albinism (Orphanet:55), Ocular albinism (Orphanet:284804), MITF-related melanoma and renal cell carcinoma predisposition syndrome (Orphanet:293822), Hypopigmentation of the skin (Orphanet:79376), NON RARE IN EUROPE: Idiopathic infantile nystagmus (Orphanet:651)

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000077	Abnormality of the kidney
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000539	Abnormality of refraction
HP:0000545	Myopia
HP:0000577	Exotropia
HP:0000587	Abnormal optic nerve morphology
HP:0000613	Photophobia
HP:0000635	Blue irides
HP:0000639	Nystagmus
HP:0000649	Abnormality of visual evoked potentials
HP:0000962	Hyperkeratosis
HP:0000995	Melanocytic nevus
HP:0001010	Hypopigmentation of the skin
HP:0001022	Albinism
HP:0001053	Hypopigmented skin patches
HP:0001072	Thickened skin
HP:0001100	Heterochromia iridis
HP:0001107	Ocular albinism
HP:0001480	Freckling
HP:0002211	White forelock
HP:0002216	Premature graying of hair
HP:0002251	Aganglionic megacolon

GWAS associations

57 associations (top):

Study	Trait	p-value
GCST000114_1	Skin pigmentation	4.000000e-10
GCST000116_1	Skin sensitivity to sun	2.000000e-06
GCST000117_2	Blue vs. green eyes	3.000000e-12
GCST000119_3	Freckles	2.000000e-11
GCST000371_7	Tanning	2.000000e-13
GCST000437_5	Melanoma	2.000000e-14
GCST000662_3	Vitiligo	2.000000e-18
GCST000710_2	Eye color	3.000000e-09
GCST000710_4	Eye color	1.000000e-15
GCST001267_8	Melanoma	2.000000e-13
GCST001509_14	Vitiligo	2.000000e-13
GCST001814_19	Age-related macular degeneration	4.000000e-06
GCST001814_6	Age-related macular degeneration	9.000000e-06
GCST001933_3	Sunburns	2.000000e-08
GCST001939_2	Tanning	5.000000e-21
GCST002514_5	Melanoma	6.000000e-08
GCST003327_3	Squamous cell carcinoma	2.000000e-20
GCST003479_7	Hair color	2.000000e-08
GCST003655_4	Cutaneous squamous cell carcinoma	3.000000e-14
GCST003726_9	Basal cell carcinoma	3.000000e-19
GCST004142_3	Melanoma	4.000000e-13
GCST004785_55	Vitiligo	1.000000e-43
GCST005580_52	Intraocular pressure	2.000000e-12
GCST005580_57	Intraocular pressure	3.000000e-12
GCST005896_1	Non-melanoma skin cancer	3.000000e-10
GCST005897_41	Low tan response	2.000000e-172
GCST006075_14	Hair color	1.000000e-100
GCST006940_16	Neurociticism	7.000000e-10
GCST006976_43	Macular thickness	1.000000e-15
GCST006988_158	Blond vs. brown/black hair color	3.000000e-71

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0003949	eye color
EFO:0003963	freckles
EFO:0004279	suntan
EFO:1001927	cutaneous squamous cell carcinoma
EFO:0004695	intraocular pressure measurement
EFO:0009260	non-melanoma skin carcinoma
EFO:0007660	neuroticism measurement
EFO:0003924	hair color
EFO:0009764	eye colour measurement
EFO:0004632	nevus count
EFO:0010176	keratinocyte carcinoma
EFO:0008111	diet measurement
EFO:0007796	parental longevity
EFO:0009762	healthspan

MeSH disease descriptors (13)

Descriptor	Name	Tree numbers
D000417	Albinism	C11.270.040; C16.320.290.040; C16.320.565.100.102; C16.320.850.080; C17.800.621.440.102; C17.800.827.080; C18.452.648.100.102
D016117	Albinism, Ocular	C11.270.040.090; C16.320.290.040.090; C16.320.565.100.102.090; C16.320.850.080.090; C17.800.621.440.102.090; C17.800.827.080.090; C18.452.648.100.102.090
D016115	Albinism, Oculocutaneous	C11.270.040.545; C16.320.290.040.100; C16.320.565.100.102.100; C16.320.850.080.100; C17.800.621.440.102.100; C17.800.827.080.100; C18.452.648.100.102.100
D020256	Choroidal Neovascularization	C11.941.160.244; C23.550.589.500.145
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D017496	Hypopigmentation	C17.800.621.440
D009216	Myopia	C11.744.636
D020417	Nystagmus, Congenital	C10.292.562.675.300; C11.590.400.300; C16.614.643
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
D013285	Strabismus	C10.292.562.887; C11.590.810
C537728	Oculocutaneous albinism type 1 (supp.)
C537729	Oculocutaneous albinism type 1B (supp.)
C536463	Waardenburg syndrome type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1973 (SINGLE PROTEIN), CHEMBL6177911 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,919,294 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL196	ASCORBIC ACID	4	1,033,030
CHEMBL443605	HEXYLRESORCINOL	4	10,669
CHEMBL537	HYDROQUINONE	4	296,240
CHEMBL140	CURCUMIN	3	93,882
CHEMBL165	RESVERATROL	3	60,144
CHEMBL50	QUERCETIN	3	74,559
CHEMBL146	BUTYLATED HYDROXYTOLUENE	2	269,416
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL232202	ARBUTIN	2	31,891
CHEMBL150	KAEMPFEROL	1	25,940

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 1.-.-.- Oxidoreductases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
neorauflavane	Inhibition	7.52	pIC50
compound 7 [PMID: 21334791]	Inhibition	6.43	pIC50

Binding affinities (BindingDB)

1 measured of 8 human assays (10 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
cycloorbicoside G	IC50	54600 nM

ChEMBL bioactivities

173 potent at pChembl≥5 of 295 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.80	IC50	16	nM	CHEMBL5594635
7.80	IC50	16	nM	CHEMBL5592150
7.80	IC50	16	nM	CHEMBL5591296
7.64	IC50	23	nM	NORARTOCARPETIN
7.22	IC50	60	nM	CHEMBL24152
7.16	IC50	70	nM	CHEMBL394855
7.10	IC50	80	nM	MORACHALCONE A
7.05	IC50	90	nM	GLABRIDIN
7.05	IC50	90	nM	OXYRESVERATROL
6.92	IC50	120	nM	BUTYLATED HYDROXYTOLUENE
6.85	IC50	140	nM	CHEMBL5562348
6.82	IC50	150	nM	CHEMBL5558420
6.81	IC50	154	nM	GLYASPERIN D
6.77	IC50	170	nM	CHEMBL4239110
6.77	IC50	170	nM	CHEMBL4743159
6.75	IC50	177	nM	GLYASPERIN C
6.75	IC50	180	nM	CHEMBL5555033
6.66	IC50	220	nM	CHEMBL5555785
6.66	IC50	220	nM	CHEMBL5542638
6.66	IC50	220	nM	CHEMBL5542520
6.66	IC50	220	nM	CHEMBL5559732
6.62	IC50	240	nM	CHEMBL317040
6.60	Ki	250	nM	CHEMBL4743159
6.60	Ki	250	nM	CHEMBL5408197
6.48	IC50	330	nM	CHEMBL98925
6.46	Ki	350	nM	CHEMBL3978212
6.46	IC50	350	nM	CHEMBL5566780
6.43	IC50	370	nM	CHEMBL499124
6.41	IC50	390	nM	CHEMBL98924
6.37	IC50	430	nM	CHEMBL491410
6.26	Ki	550	nM	CHEMBL5399906
6.25	IC50	560	nM	HEXYLRESORCINOL
6.17	IC50	680	nM	CHEMBL1760463
6.16	IC50	700	nM	CHEMBL1794031
6.14	IC50	720	nM	CHEMBL5556099
6.14	IC50	730	nM	CHEMBL489989
6.11	IC50	780	nM	CHEMBL430491
6.11	IC50	770	nM	CHEMBL1760462
6.08	IC50	830	nM	CHEMBL1760464
6.07	IC50	850	nM	CHEMBL5557086
6.05	IC50	900	nM	CHEMBL4743159
6.05	IC50	890	nM	CHEMBL5557324
6.04	Ki	920	nM	CHEMBL4743159
6.01	IC50	980	nM	CHEMBL458395
6.00	IC50	1000	nM	KAEMPFEROL
6.00	IC50	1000	nM	CHEMBL4473314
6.00	IC50	1000	nM	SUBAMOLIDE A
5.99	Ki	1020	nM	CHEMBL5632644
5.97	IC50	1070	nM	CHEMBL2078992
5.96	IC50	1100	nM	CHEMBL4743159

PubChem BioAssay actives

198 with measured affinity, of 881 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[2-(2-methyl-5-propan-2-ylphenoxy)-2-oxoethyl] 3,5-dihydroxybenzoate	2112482: Inhibition of tyrosinase (unknown origin)	ic50	0.0160	uM
[2-(2-methyl-5-propan-2-ylphenoxy)-2-oxoethyl] 3,4,5-trihydroxybenzoate	2112482: Inhibition of tyrosinase (unknown origin)	ic50	0.0160	uM
[2-(2-methyl-5-propan-2-ylphenoxy)-2-oxoethyl] (E)-3-(2,4-dihydroxyphenyl)prop-2-enoate	2112482: Inhibition of tyrosinase (unknown origin)	ic50	0.0160	uM
2-(2,4-dihydroxyphenyl)-5,7-dihydroxychromen-4-one	1504875: Inhibition of tyrosinase (unknown origin) using L-dihydroxyphenylalanine as substrate preincubated for 30 mins followed by substrate addition measured for 7 mins by spectrophotometric analysis	ic50	0.0230	uM
(E)-1,3-bis(2,4-dihydroxyphenyl)prop-2-en-1-one	1611934: Inhibition of tyrosinase (unknown origin)	ic50	0.0700	uM
(E)-1-[2,4-dihydroxy-3-(3-methylbut-2-enyl)phenyl]-3-(2,4-dihydroxyphenyl)prop-2-en-1-one	1611934: Inhibition of tyrosinase (unknown origin)	ic50	0.0800	uM
4-[(3R)-8,8-dimethyl-3,4-dihydro-2H-pyrano[2,3-f]chromen-3-yl]benzene-1,3-diol	1484036: Inhibition of tyrosinase (unknown origin) using L-tyrosine as substrate preincubated for 5 mins followed by substrate addition	ic50	0.0900	uM
4-[(E)-2-(3,5-dihydroxyphenyl)ethenyl]benzene-1,3-diol	1717732: Inhibition of human tyrosinase expressed in HEK293 cells using L-tyrosine and DOPA as substrate	ic50	0.0900	uM
butylated hydroxytoluene	2112482: Inhibition of tyrosinase (unknown origin)	ic50	0.1200	uM
N-[(2E)-2-[(2,4-dihydroxyphenyl)methylidene]-1-oxo-3H-inden-4-yl]acetamide	2067611: Inhibition of tyrosinase in human MNT-1 cells using L-DOPA as substrate preincubated for 10 mins followed by substrate addition measured after 180 mins by absorbance based spectramax microplate reader assay	ic50	0.1400	uM
N-[(2E)-2-[(2,4-dihydroxyphenyl)methylidene]-1-oxo-3H-inden-4-yl]propanamide	2067611: Inhibition of tyrosinase in human MNT-1 cells using L-DOPA as substrate preincubated for 10 mins followed by substrate addition measured after 180 mins by absorbance based spectramax microplate reader assay	ic50	0.1500	uM
4-[(3R)-5,7-dimethoxy-6-(3-methylbut-2-enyl)-3,4-dihydro-2H-chromen-3-yl]benzene-1,3-diol	1301471: Inhibition of tyrosinase (unknown origin) using L-tyrosine as substrate assessed as oxidation of L-tyrosine after 15 mins	ic50	0.1540	uM
(E)-1-[2,4-dihydroxy-3-[(E)-4-hydroxy-3-methylbut-2-enyl]phenyl]-3-(2,4-dihydroxyphenyl)prop-2-en-1-one	1611934: Inhibition of tyrosinase (unknown origin)	ic50	0.1700	uM
N-[4-(2,4-dihydroxyphenyl)-1,3-thiazol-2-yl]-2-methylpropanamide	2067611: Inhibition of tyrosinase in human MNT-1 cells using L-DOPA as substrate preincubated for 10 mins followed by substrate addition measured after 180 mins by absorbance based spectramax microplate reader assay	ic50	0.1700	uM
4-[(3R)-7-hydroxy-5-methoxy-6-(3-methylbut-2-enyl)-3,4-dihydro-2H-chromen-3-yl]benzene-1,3-diol	1301471: Inhibition of tyrosinase (unknown origin) using L-tyrosine as substrate assessed as oxidation of L-tyrosine after 15 mins	ic50	0.1770	uM
N-[(2E)-2-[(2,4-dihydroxyphenyl)methylidene]-1-oxo-3H-inden-4-yl]butanamide	2067611: Inhibition of tyrosinase in human MNT-1 cells using L-DOPA as substrate preincubated for 10 mins followed by substrate addition measured after 180 mins by absorbance based spectramax microplate reader assay	ic50	0.1800	uM
[(E)-[4-[[1-[(3,4-dichlorophenyl)methyl]triazol-4-yl]methoxy]phenyl]methylideneamino]thiourea	2078306: Competitive inhibition of His-tagged human tyrosinase expressed in HEK293 cells	ic50	0.2200	uM
[(E)-[4-[[1-[(4-fluorophenyl)methyl]triazol-4-yl]methoxy]phenyl]methylideneamino]thiourea	2078306: Competitive inhibition of His-tagged human tyrosinase expressed in HEK293 cells	ic50	0.2200	uM
[(E)-[4-[[1-[(3-methylphenyl)methyl]triazol-4-yl]methoxy]phenyl]methylideneamino]thiourea	2078306: Competitive inhibition of His-tagged human tyrosinase expressed in HEK293 cells	ic50	0.2200	uM
[(E)-[4-[[1-[(4-methylphenyl)methyl]triazol-4-yl]methoxy]phenyl]methylideneamino]thiourea	2078306: Competitive inhibition of His-tagged human tyrosinase expressed in HEK293 cells	ic50	0.2200	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[(5-hydroxy-4-oxopyran-2-yl)methoxycarbonylamino]-3-phenylpropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid	215966: Inhibitory activity against mushroom tyrosinase	ic50	0.2400	uM
(2E)-2-[(2,4-dihydroxyphenyl)methylidene]-4-hydroxy-3H-inden-1-one	2002044: Inhibition of C-terminal His-tagged truncated form of human tyrosinase (1 to 456 residues) expressed in HEK293T cells using L-DOPA as substrate assessed as inhibition constant incubated for 1 hr by microplate reader analysis	ki	0.2500	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[(5-hydroxy-4-oxopyran-2-yl)methoxycarbonylamino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid	215966: Inhibitory activity against mushroom tyrosinase	ic50	0.3300	uM
N-[(2E)-2-[(2,4-dihydroxyphenyl)methylidene]-1-oxo-3H-inden-4-yl]-2-methylpropanamide	2067611: Inhibition of tyrosinase in human MNT-1 cells using L-DOPA as substrate preincubated for 10 mins followed by substrate addition measured after 180 mins by absorbance based spectramax microplate reader assay	ic50	0.3500	uM
1-hydroxy-5-[(Z)-(6-hydroxy-3-oxo-1-benzofuran-2-ylidene)methyl]pyridin-2-one	1331359: Inhibition of recombinant human tyrosinase expressed in baculovirus infected Sf9 cells assessed as diphenolase activity using L-DOPA as substrate by UV-vis spectrophotometry	ki	0.3500	uM
4-[2-(2,4-dihydroxyphenyl)ethyl]benzene-1,3-diol	590115: Inhibition of Tyrosinase	ic50	0.3700	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[(5-hydroxy-4-oxopyran-2-yl)methoxycarbonylamino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid	215966: Inhibitory activity against mushroom tyrosinase	ic50	0.3900	uM
(2S,3R,4S,5R)-2-[4-[2-(2,4-dihydroxyphenyl)ethyl]-3-hydroxyphenoxy]oxane-3,4,5-triol	590115: Inhibition of Tyrosinase	ic50	0.4300	uM
(2Z)-2-[(2,4-dihydroxyphenyl)methylidene]-7-hydroxy-1-benzofuran-3-one	2002044: Inhibition of C-terminal His-tagged truncated form of human tyrosinase (1 to 456 residues) expressed in HEK293T cells using L-DOPA as substrate assessed as inhibition constant incubated for 1 hr by microplate reader analysis	ki	0.5500	uM
Hexylresorcinol	1248348: Inhibition of tyrosinase (unknown origin) using L-DOPA as substrate assessed as formation of dopachrome by spectrophotometric analysis	ic50	0.5600	uM
(2S,3R,4S,5S,6R)-2-[(2R,3S,4R,5R,6S)-6-[4-[2-(2,4-dihydroxyphenyl)ethyl]-3-hydroxyphenoxy]-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol	590115: Inhibition of Tyrosinase	ic50	0.6800	uM
(2E)-4-amino-2-[(2,4-dihydroxyphenyl)methylidene]-3H-inden-1-one	2067611: Inhibition of tyrosinase in human MNT-1 cells using L-DOPA as substrate preincubated for 10 mins followed by substrate addition measured after 180 mins by absorbance based spectramax microplate reader assay	ic50	0.7200	uM
(2S,3R,4S,5R)-2-[4-[2-(2,4-dihydroxyphenyl)ethyl]-3-[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxyphenoxy]oxane-3,4,5-triol	590115: Inhibition of Tyrosinase	ic50	0.7300	uM
(2S,3R,4S,5S,6R)-2-[4-[2-(2,4-dihydroxyphenyl)ethyl]-3-hydroxyphenoxy]-6-(hydroxymethyl)oxane-3,4,5-triol	590115: Inhibition of Tyrosinase	ic50	0.7700	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[(5-hydroxy-4-oxopyran-2-yl)methoxycarbonylamino]-3-(1H-indol-3-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid	215966: Inhibitory activity against mushroom tyrosinase	ic50	0.7800	uM
(2R,3R,4S,5S,6R)-2-[(2R,3S,4R,5R,6S)-6-[4-[2-(2,4-dihydroxyphenyl)ethyl]-3-hydroxyphenoxy]-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol	590115: Inhibition of Tyrosinase	ic50	0.8300	uM
(2S)-2-amino-N-[(2E)-2-[(2,4-dihydroxyphenyl)methylidene]-1-oxo-3H-inden-4-yl]propanamide	2067611: Inhibition of tyrosinase in human MNT-1 cells using L-DOPA as substrate preincubated for 10 mins followed by substrate addition measured after 180 mins by absorbance based spectramax microplate reader assay	ic50	0.8500	uM
(2E)-2-[(2,4-dihydroxyphenyl)methylidene]-4-(methylamino)-3H-inden-1-one	2067611: Inhibition of tyrosinase in human MNT-1 cells using L-DOPA as substrate preincubated for 10 mins followed by substrate addition measured after 180 mins by absorbance based spectramax microplate reader assay	ic50	0.8900	uM
(2S)-2-(2,4-dihydroxyphenyl)-5,7-dihydroxy-2,3-dihydrochromen-4-one	1611934: Inhibition of tyrosinase (unknown origin)	ic50	0.9800	uM
(3Z,4R,5R)-4-hydroxy-5-methoxy-5-methyl-3-tetradecylideneoxolan-2-one	1717710: Inhibition of tyrosinase in human neonatal foreskin epidermal melanocyte cells using L-tyrosine and L-DOPA as substrate preincubated for 2 days followed by cell lysis and subsequent substrate addition and measured after 3 hr by spectrophotometric method	ic50	1.0000	uM
3,5,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one	1301471: Inhibition of tyrosinase (unknown origin) using L-tyrosine as substrate assessed as oxidation of L-tyrosine after 15 mins	ic50	1.0000	uM
(3Z,4R)-4-hydroxy-5-methylidene-3-tetradecylideneoxolan-2-one	1717710: Inhibition of tyrosinase in human neonatal foreskin epidermal melanocyte cells using L-tyrosine and L-DOPA as substrate preincubated for 2 days followed by cell lysis and subsequent substrate addition and measured after 3 hr by spectrophotometric method	ic50	1.0000	uM
[4-(4-hydroxyphenyl)piperazin-1-yl]-(2-methoxyphenyl)methanone	2138731: Binding affinity to human tyrosinase using l-DOPA as substrate assessed as inhibition constant by Michaelis-Menten plot analysis	ki	1.0200	uM
methyl 2-[3-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-2,5-dioxo-4,4-diphenylimidazolidin-1-yl]acetate	1653002: Inhibition of tyrosinase (unknown origin)	ic50	1.0700	uM
4-[2-(propan-2-ylamino)-1,3-thiazol-4-yl]benzene-1,3-diol	1978470: Inhibition of human tyrosinase using L-DOPA as substrate incubated for 10 to 20 mins by MBTH dye based assay	ic50	1.1000	uM
2-hydroxy-5-propan-2-ylcyclohepta-2,4,6-trien-1-one	1167965: Competitive inhibition of tyrosinase in human G-361 cells incubated for 10 mins measured for 2 hrs by MBTH-based spectrophotometry	ic50	1.1500	uM
N-[4-(2,4-dihydroxyphenyl)-1,3-thiazol-2-yl]-2,2-dimethylpropanamide	1717730: Inhibition of human tyrosinase using L- DOPA as substrate by MBTH based assay	ic50	1.4000	uM
(2S,3R,4S,5S,6R)-2-[(2R,3S,4R,5R,6R)-6-[(2R)-4-(2,4-dihydroxyphenyl)butan-2-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol	1248348: Inhibition of tyrosinase (unknown origin) using L-DOPA as substrate assessed as formation of dopachrome by spectrophotometric analysis	ic50	1.5100	uM
4-[2-(3,5-dihydroxyphenyl)ethyl]benzene-1,3-diol	276018: Inhibition of tyrosinase	ic50	1.6000	uM
(2S,3R,4S,5R)-2-[2-[2-(2,4-dihydroxyphenyl)ethyl]-5-hydroxyphenoxy]oxane-3,4,5-triol	590115: Inhibition of Tyrosinase	ic50	1.6000	uM

CTD chemical–gene interactions

68 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Colforsin	increases expression, decreases reaction, affects cotreatment, decreases activity, decreases expression (+1 more)	4
Melanins	increases abundance, increases chemical synthesis, increases oxidation, increases reaction, decreases expression (+4 more)	4
Plant Extracts	affects cotreatment, decreases expression, decreases activity	3
Quercetin	increases response to substance, decreases reaction, increases activity, affects activity, affects expression (+1 more)	3
5,7-dimethoxycoumarin	increases activity, increases expression, affects cotreatment	2
caffeic acid phenethyl ester	increases response to substance, decreases reaction, increases oxidation, affects response to substance, affects abundance (+1 more)	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases activity, increases expression, decreases expression	2
Resveratrol	affects cotreatment, decreases expression, affects localization, decreases activity	2
Copper	increases abundance, increases chemical synthesis, increases oxidation, increases reaction, affects cotreatment (+2 more)	2
Valproic Acid	increases activity, increases expression, affects cotreatment	2
bisphenol F	affects cotreatment, decreases methylation	1
3,4-dihydroxyphenylpropionic acid	decreases abundance, increases oxidation	1
ferulic acid	increases oxidation, decreases abundance	1
beta-ionone	increases expression	1
amentoflavone	decreases activity	1
kojic acid	increases expression	1
ethyl-p-hydroxybenzoate	affects response to substance	1
4-hydroxy-2-nonenal	decreases expression	1
bathocuproine sulfonate	decreases reaction, increases activity	1
cinnamic acid	increases oxidation, decreases abundance	1
cupric chloride	decreases reaction, increases activity	1
ethylenediamine	decreases reaction, increases oxidation	1
resorcinol	decreases activity	1
9-cis-retinal	increases expression, decreases reaction	1
hydroquinone	increases expression	1
3-phenylpropionic acid	increases oxidation, decreases abundance	1
caffeic acid	increases oxidation, decreases abundance	1
artemisic acid	decreases expression	1
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide	decreases activity	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects cotreatment, decreases expression	1

ChEMBL screening assays

211 unique, capped per target: 209 binding, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1013463	Binding	Inhibition of tyrosinase at 5 uM	Synthesis and in vitro biological activity of retinyl polyhydroxybenzoates, novel hybrid retinoid derivatives. — Bioorg Med Chem Lett
CHEMBL4010827	ADMET	Drug metabolism assessed as tyrosinase (unknown origin)-mediated redox transformation by measuring sonnerphenolic C formation at 10 mM in presence of vitamin C by HPLC analysis	Chemical synthesis, redox transformation, and identification of sonnerphenolic C, an antioxidant in Acer nikoense. — Bioorg Med Chem Lett

Cellosaurus cell lines

15 cell lines: 7 induced pluripotent stem cell, 4 embryonic stem cell, 4 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4GS	chHES-478	Embryonic stem cell	Female
CVCL_A7R2	SEES3-1V human TYR, clone1	Embryonic stem cell	Male
CVCL_A7R3	SEES3-1V human TYR, clone2	Embryonic stem cell	Male
CVCL_A7R4	SEES3-1V human TYR, clone3	Embryonic stem cell	Male
CVCL_AM55	GM11292	Transformed cell line	Female
CVCL_AM58	GM11296	Transformed cell line	Male
CVCL_AM59	GM11297	Transformed cell line	Male
CVCL_AM60	GM11345	Transformed cell line	Female
CVCL_C1XT	WTSIi253-A-2	Induced pluripotent stem cell	Male
CVCL_D3BH	Tyr1	Induced pluripotent stem cell

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00001596	PHASE2	COMPLETED	Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome
NCT01663935	PHASE2	TERMINATED	Vision Response to Dopamine Replacement
NCT01176435	PHASE2	COMPLETED	Trial of L-DOPA as a Treatment to Improve Vision in Albinism
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT00467831	PHASE1/PHASE2	TERMINATED	Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
NCT07313618	EARLY_PHASE1	RECRUITING	Safety and Efficacy of a Single Suprachoroidal Injection of JWK010 Gene Therapy in Subjects With Oculocutaneous Albinism Type 1 (OCA1)
NCT00001153	Not specified	COMPLETED	Visual Function and Ocular Pigmentation in Albinism
NCT00808106	Not specified	COMPLETED	Clinical, Cellular, and Molecular Investigation Into Oculocutaneous Albinism
NCT02200263	Not specified	COMPLETED	The Effects of Lutein and Zeaxanthin Supplementation on Vision in Patients With Albinism
NCT04068961	Not specified	COMPLETED	New Strategies of Genetic Study of Patients With Oculocutaneous Albinism
NCT06138509	Not specified	RECRUITING	Peripheral Serotonin and Albinism