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 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 890 total — 120 pathogenic, 125 likely-pathogenic (top 4% of genes corpus-wide)
• GTEx eGene: eQTL in 2 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 42
• Drug target: yes — 3 curated mechanism-of-action drugs; 10 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 2 — Mequinol, Monobenzone
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.35 (unconstrained)
• MANE Select transcript: NM_000372
• Interaction hub: 2,296 STRING partners (top 5% of genes corpus-wide)

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

MANE Select: ENST00000263321

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 5: 1

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.

Highest expression (Bgee): pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis, upper leg skin, skin of leg, skin of abdomen.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TYR is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 2 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

2 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Not Sun Exposed Suprapubic	eqtl	1.0e-03	-0.28	11:89042605:A:C
Skin Sun Exposed Lower leg	eqtl	4.9e-03	+0.12	11:89059433:A:C

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 204 tissues 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
trigeminal ganglion	UBERON:0001675	41.24	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
mouth mucosa	UBERON:0003729	40.81	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
cortical plate	UBERON:0005343	40.20	silver quality
jejunum	UBERON:0002115	40.18	gold quality
mammary duct	UBERON:0001765	40.08	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality
globus pallidus	UBERON:0001875	39.99	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
deltoid	UBERON:0001476	39.83	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
parotid gland	UBERON:0001831	39.81	gold quality
oocyte	CL:0000023	39.80	gold quality
urethra	UBERON:0000057	39.80	gold quality
heart right ventricle	UBERON:0002080	39.79	gold quality
minor salivary gland	UBERON:0001830	39.78	gold quality
pericardium	UBERON:0002407	39.77	gold quality
layer of synovial tissue	UBERON:0007616	39.77	gold quality
endothelial cell	CL:0000115	39.75	gold quality
synovial joint	UBERON:0002217	39.70	gold quality
dorsal root ganglion	UBERON:0000044	39.68	gold quality
bronchial epithelial cell	CL:0002328	39.65	gold quality
decidua	UBERON:0002450	39.65	gold quality
bronchus	UBERON:0002185	39.64	gold quality
tendon of biceps brachii	UBERON:0008188	39.60	gold quality
inferior vagus X ganglion	UBERON:0005363	39.57	gold quality
superior surface of tongue	UBERON:0007371	39.56	gold quality
pylorus	UBERON:0001166	39.55	gold quality
renal medulla	UBERON:0000362	39.53	gold quality
pons	UBERON:0000988	39.51	gold quality
thymus	UBERON:0002370	39.50	gold quality
medulla oblongata	UBERON:0001896	39.48	gold quality
superior vestibular nucleus	UBERON:0007227	39.47	gold quality
cardia of stomach	UBERON:0001162	39.46	gold quality
colonic mucosa	UBERON:0000317	39.45	gold quality
parietal pleura	UBERON:0002400	39.45	gold quality
sperm	CL:0000019	39.40	gold quality
Brodmann (1909) area 23	UBERON:0013554	39.40	gold quality
dorsal plus ventral thalamus	UBERON:0001897	39.38	gold quality
tongue	UBERON:0001723	39.37	gold quality
cerebellar vermis	UBERON:0004720	39.37	gold quality
subthalamic nucleus	UBERON:0001906	39.35	gold quality
ventral tegmental area	UBERON:0002691	39.35	gold quality
trachea	UBERON:0003126	39.33	gold quality
parietal lobe	UBERON:0001872	39.32	gold quality
vena cava	UBERON:0004087	39.31	gold quality
pharyngeal mucosa	UBERON:0000355	39.27	gold quality
entorhinal cortex	UBERON:0002728	39.24	gold quality
substantia nigra pars compacta	UBERON:0001965	39.23	gold quality
visceral pleura	UBERON:0002401	39.23	gold quality
postcentral gyrus	UBERON:0002581	39.23	gold quality
body of tongue	UBERON:0011876	39.22	gold quality
medial globus pallidus	UBERON:0002477	39.18	gold quality
trabecular bone tissue	UBERON:0002483	39.18	gold quality
substantia nigra pars reticulata	UBERON:0001966	39.11	gold quality
tibial artery	UBERON:0007610	39.05	gold quality
nasal cavity epithelium	UBERON:0005384	39.04	gold quality
lateral nuclear group of thalamus	UBERON:0002736	39.00	gold quality
corpus epididymis	UBERON:0004359	38.98	gold quality
saliva-secreting gland	UBERON:0001044	38.96	gold quality
popliteal artery	UBERON:0002250	38.94	gold quality
tibia	UBERON:0000979	38.93	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

HPA expression

RNA tissue specificity: Tissue enriched

34 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skin 1	tissue	29.8	high
Breast	tissue	0.8	not detected
Ventral forebrain	tissue	0.8
Corpus callosum	tissue	0.7
Basal ganglia	tissue	0.6	not detected
Periaqueductal gray	tissue	0.6
Substantia nigra	tissue	0.5
Spinal cord	tissue	0.5
Hippocampal formation	tissue	0.5
Septum	tissue	0.5
Putamen	tissue	0.4
Amygdala	tissue	0.4
Midbrain	tissue	0.4
Thalamus	tissue	0.4
Hypothalamus	tissue	0.4
Cerebral cortex	tissue	0.3	not detected
Pons	tissue	0.3
Medulla oblongata	tissue	0.3
Superior colliculi	tissue	0.3
Olfactory bulb	tissue	0.3
Insular cortex	tissue	0.3
Prefrontal cortex	tissue	0.2
Testis	tissue	0.2	not detected
Entorhinal cortex	tissue	0.2
Retrosplenial and cingulate cortex	tissue	0.2
Retrosplenial cortex	tissue	0.2
Temporal cortex	tissue	0.2
Occipital cortex	tissue	0.2
Retina	tissue	0.1	high
Motor cortex	tissue	0.1
Bone marrow	tissue	0.1	not detected
Caudate putamen	tissue	0.1
Somatosensory cortex	tissue	0.1
Hair	tissue	-1.0	high

Brain sub-regions (HPA Brain Atlas): detected in 15; highest nTPM — White matter (0.7), Dorsal hippocampus (0.5), Ventral spinal cord (0.5), Subiculum (0.4), Dorsal spinal cord (0.3).

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)

Targeting TYR by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

21 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1.11e-21, LOEUF 1.35, missense Z -0.846 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000263321 — one region, missense o/e 1.13.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98880) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 58 distinct phenotype terms.

Mouse phenotype (MP)	Records
absent coat pigmentation	23
diluted coat color	14
absent eye pigmentation	14
abnormal coat/hair pigmentation	12
absent skin pigmentation	7
decreased eye pigmentation	7
ocular albinism	5
embryonic lethality before implantation, complete penetrance	4
abnormal eye pigmentation	3
premature death	3
neonatal lethality, complete penetrance	3
perinatal lethality, complete penetrance	3
embryonic lethality at implantation, complete penetrance	3
absent hair follicle melanin granules	2
mottled coat	2
induced chromosome breakage	2
abnormal hair follicle melanogenesis	2
variegated coat color	2
hypopigmentation	2
abnormal ear pigmentation	1
abnormal cell morphology	1
irregular coat pigmentation	1
belly spot	1
shiny fur	1
abnormal retina photoreceptor morphology	1

+33 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gorilla gorilla gorilla	Q9BDE0	99.8%	Diamond
Gallus gallus	P55024	97.8%	Diamond
Coturnix japonica	Q08410	97.8%	Diamond
Pelophylax nigromaculatus	Q04604	94.5%	Diamond
Pelophylax lessonae	Q0MVP0	94.5%	Diamond
Canis lupus familiaris	P54834	94.2%	Diamond
Felis catus	P55033	94.2%	Diamond
Bos taurus	Q8WN57	90.5%	Diamond
Sus scrofa	Q4R1H1	90.4%	Diamond
Streptomyces lincolnensis	P55023	82.5%	Diamond
Pelodiscus sinensis	P55026	78.8%	Diamond
Ambystoma mexicanum	P55027	75.1%	Diamond
Carassius auratus	P55028	69.0%	Diamond
Oryzias latipes	P55025	63.0%	Diamond
Streptomyces griseus subsp. griseus NBRC 13350	B1VTI5	49.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GRM5-AS1	ncRNA	100873989
GRM5	protein-coding	2915
NOX4	protein-coding	50507
CTSC	protein-coding	1075

Protein

Protein identifiers

Tyrosinase — P14679 (reviewed: P14679)

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

All UniProt accessions (2): L8B082, P14679

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-like	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)

• 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 by resolution:

PDB	Title	Method	Resolution (Å)
7RK7	The complex between TIL 1383i TCR and human Class I MHC HLA-A2 with the bound …	X-RAY DIFFRACTION	2.54

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Transporters, Predicted membrane proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of amino acid metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH enhanced · IF enhanced

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)

Position	Role
367	Cu cation
390	Cu cation
180	Cu cation
202	Cu cation
211	Cu cation
363	Cu cation

Glycosylation sites (6)

Type	Positions
N-linked (glcnac…) asparagine	86, 111, 161, 230, 337, 371

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-5662702	Melanin biosynthesis	curated
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation	curated
R-HSA-1266738	Developmental Biology	—
R-HSA-9856651	MITF-M-dependent gene expression	—
R-HSA-9730414	MITF-M-regulated melanocyte development	—
R-HSA-1430728	Metabolism	—
R-HSA-71291	Metabolism of amino acids and derivatives	—

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), 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), response to cAMP (GO:0051591), developmental pigmentation (GO:0048066), eye pigmentation (GO:0048069)

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

Reactome top-level categories

5 top-level categories:

Category	Pathways
Metabolism of amino acids and derivatives	1
MITF-M-dependent gene expression	1
Metabolism	1
Developmental Biology	1
MITF-M-regulated melanocyte development	1

GO top-level categories

34 GO namespaces:

Category	Terms
pigment biosynthetic process	2
response to light stimulus	2
response to oxygen-containing compound	2
cellular anatomical structure	2
melanin biosynthetic process	1
eye pigment metabolic process	1
sensory perception of light stimulus	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
response to purine-containing compound	1
response to organophosphorus	1
pigmentation	1
developmental pigmentation	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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 25 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
melanin biosynthetic process	BP	direct assay
response to blue light	BP	direct assay
cytoplasm	CC	direct assay
perinuclear region of cytoplasm	CC	direct assay
copper ion binding	MF	mutant phenotype
identical protein binding	MF	direct assay
tyrosinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,296 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TYR	OCA2	Q04671	955
TYR	MITF	O75030	952
TYR	MC1R	Q01726	948
TYR	PMEL	P40967	941
TYR	SLC45A2	Q9UMX9	932
TYR	MLANA	Q16655	877
TYR	SLC24A5	Q71RS6	864
TYR	GPR143	P51810	859
TYR	SOX10	P56693	794
TYR	ASIP	P42127	778
TYR	POMC	P01189	770
TYR	CTAG1A	P78358	748
TYR	RAB38	P57729	732
TYR	MAGEA3	P43357	717
TYR	PAX3	P23760	713

IntAct

Human interaction partners of TYR in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
GPR143	physical association	0.520	4

BioGRID (6 interactions; top human partners by supporting records): KRAS (Synthetic Lethality), PRKD2 (Affinity Capture-MS), RAF1 (Proximity Label-MS), SYVN1 (Affinity Capture-Western)

SIGNOR signaling

showing 2 of 3 signaling interactions:

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

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
★ DCT-TYR complex	2	TYR, DCT
★ GPR143-TYR complex	2	GPR143, TYR
★ TYR homodimer	1	TYR

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
GPR143	ligand	Signaling by Serotonin/Dopamine

Disease & clinical

Genetic variants

Variant evidence for TYR: 890 ClinVar records (245 pathogenic / likely pathogenic); 57 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	120
Likely pathogenic	125
Uncertain significance	239
Likely benign	211
Benign	12

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 245 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
3774	NM_000372.5(TYR):c.1118C>A (p.Thr373Lys)	Pathogenic	criteria provided, multiple submitters, no conflicts	30
99583	NM_000372.5(TYR):c.832C>T (p.Arg278Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	26
3772	NM_000372.5(TYR):c.242C>T (p.Pro81Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	22
3796	NM_000372.5(TYR):c.896G>A (p.Arg299His)	Pathogenic	criteria provided, multiple submitters, no conflicts	19
3775	NM_000372.5(TYR):c.1147G>A (p.Asp383Asn)	Pathogenic	criteria provided, multiple submitters, no conflicts	16
99542	NM_000372.5(TYR):c.1204C>T (p.Arg402Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	16
3771	NM_000372.5(TYR):c.929dup (p.Arg311fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	14
3787	NM_000372.5(TYR):c.732_733del (p.Cys244_Asp245delinsTer)	Pathogenic	criteria provided, multiple submitters, no conflicts	13
3790	NM_000372.5(TYR):c.164G>A (p.Cys55Tyr)	Pathogenic	criteria provided, multiple submitters, no conflicts	12
99570	NM_000372.5(TYR):c.572del (p.Gly191fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	11
3782	NM_000372.5(TYR):c.1265G>A (p.Arg422Gln)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
3793	NM_000372.5(TYR):c.61C>T (p.Pro21Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
373911	NM_000372.5(TYR):c.74dup (p.Ser26fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	9
99574	NM_000372.5(TYR):c.649del (p.Arg217fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
379657	NM_000372.5(TYR):c.976C>T (p.Gln326Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	7

Per-variant reference — Sugi Variant

Explore TYR’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 767):

Position(s)	Effect	Δscore	Sites
11:89178699	donor_gain	1.0000
11:89178773–89178774	donor_loss	0.9900	5
11:89227815	acceptor_gain	0.9900
11:89227821–89227822	acceptor_loss	0.9900	6
11:89227971–89227972	donor_loss	0.9900	6
11:89284771–89284772	acceptor_gain	0.9900	2
11:89284771–89284772	acceptor_loss	0.9900	4
11:89191416	donor_gain	0.9800
11:89227816	acceptor_gain	0.9800
11:89227970	donor_loss	0.9800	2

AlphaMissense

988 missense substitutions predicted likely pathogenic (of 3,516 scored), across 234 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D383	8	0.983	0.993
D394	8	0.979	0.992
H211	8	0.972	0.990
H367	8	0.969	0.988
H390	8	0.968	0.990
F207	8	0.963	0.994
H363	8	0.962	0.979
F386	8	0.960	0.994
H202	8	0.959	0.985
H180	8	0.953	0.974
F340	8	0.946	0.991
H389	8	0.880	0.985
D75	8	0.857	0.933
F269	8	0.835	0.937
H420	8	0.823	0.946
W238	7	0.983	0.997
W400	7	0.982	0.996
C247	7	0.978	0.992
C276	7	0.974	0.990
C289	7	0.966	0.987

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Skin Cutaneous Melanoma)

Disease associations

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

GenCC curated gene-disease

5 curated gene-disease records:

Disease	Classification	Inheritance	Records
oculocutaneous albinism type 1A	Definitive	Autosomal recessive	5
oculocutaneous albinism type 1B	Strong	Autosomal recessive	2
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

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

1 validity classifications:

Disease	Classification	Inheritance
oculocutaneous albinism type 1	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (6 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

6 panels:

Panel	Rating
Albinism or congenital nystagmus	green
DDG2P	green
Infantile nystagmus	green
Ocular and oculo-cutaneous albinism	green
Paediatric disorders	green
Pigmentary skin disorders	green

Mondo (16): oculocutaneous albinism type 1B (MONDO:0011749), oculocutaneous albinism type 1A (MONDO:0008745), oculocutaneous albinism type 1 (MONDO:0018135), oculocutaneous albinism (MONDO:0018910), ocular albinism (MONDO:0017304), retinal disorder (MONDO:0005283), albinism (MONDO:0043209), strabismus (MONDO:0003432), hypopigmentation of the skin (MONDO:0019290), temperature-sensitive oculocutaneous albinism type 1 (MONDO:0018137), myopia (MONDO:0001384), pathologic nystagmus (MONDO:0004843), foveal hypoplasia (MONDO:0044203), choroidal neovascularization (MONDO:0810000), minimal pigment oculocutaneous albinism type 1 (MONDO:0018136), Waardenburg syndrome type 2 (MONDO:0019517)

Orphanet (7): 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), Hypopigmentation of the skin (Orphanet:79376)

HPO phenotypes

42 phenotypes (HPO-id order):

HPO	Term
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
HP:0002671	Basal cell carcinoma
HP:0002861	Melanoma
HP:0003577	Congenital onset
HP:0004414	Abnormality of the pulmonary artery
HP:0005599	Hypopigmentation of hair
HP:0006739	Squamous cell carcinoma of the skin
HP:0007663	Reduced visual acuity
HP:0007703	Abnormal retinal pigmentation
HP:0007730	Iris hypopigmentation
HP:0007750	Hypoplasia of the fovea
HP:0007894	Fundus hypopigmentation
HP:0011364	White hair
HP:0200098	Absent skin pigmentation

GWAS associations

showing 30 of 57 associations:

Study	Trait	p-value
GCST006988_134	Blond vs. brown/black hair color	2e-200
GCST010302_7	Cutaneous melanoma or hair colour	4e-199
GCST005897_16	Low tan response	2e-172
GCST006075_14	Hair color	1e-100
GCST006988_23	Blond vs. brown/black hair color	3e-71
GCST010304_16	Cutaneous malignant melanoma	4e-70
GCST008870_16	Keratinocyte cancer (MTAG)	9e-62
GCST006988_153	Blond vs. brown/black hair color	8e-59
GCST008871_49	Basal cell carcinoma	7e-51
GCST010303_5	Nevus count or cutaneous melanoma	1e-48
GCST004785_55	Vitiligo	1e-43
GCST010148_16	Cutaneous squamous cell carcinoma	2e-38
GCST90013410_24	Basal cell carcinoma	5e-33
GCST006989_35	Brown vs. black hair color	2e-27
GCST006989_36	Brown vs. black hair color	5e-24
GCST008872_17	Squamous cell carcinoma	2e-23
GCST012442_29	Age-related hearing impairment	2e-21
GCST001939_2	Tanning	5e-21
GCST003327_3	Squamous cell carcinoma	2e-20
GCST003726_9	Basal cell carcinoma	3e-19
GCST000662_3	Vitiligo	2e-18
GCST000710_4	Eye color	1e-15
GCST006976_93	Macular thickness	1e-15
GCST000437_5	Melanoma	2e-14
GCST003655_4	Cutaneous squamous cell carcinoma	3e-14
GCST000371_7	Tanning	2e-13
GCST001267_8	Melanoma	2e-13
GCST001509_14	Vitiligo	2e-13
GCST004142_3	Melanoma	4e-13
GCST007451_6	Skin, hair and eye pigmentation (multivariate analysis)	7e-13

EFO canonical traits (from GWAS)

14 canonical traits:

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

12 disease descriptors:

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
D017496	Hypopigmentation	C17.800.621.440
D009216	Myopia	C11.744.636
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
D012164	Retinal Diseases	C11.768
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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the TYR protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

3 curated-mechanism drugs:

Drug	Modality	Max phase
MEQUINOL	Small molecule	4
MONOBENZONE	Small molecule	4
ARBUTIN	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,937,948 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

10 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL196	ASCORBIC ACID	4	1,043,187
CHEMBL443605	HEXYLRESORCINOL	4	10,814
CHEMBL537	HYDROQUINONE	4	297,955
CHEMBL140	CURCUMIN	3	95,185
CHEMBL50	QUERCETIN	3	75,572
CHEMBL165	RESVERATROL	3	61,047
CHEMBL232202	ARBUTIN	2	32,147
CHEMBL146	BUTYLATED HYDROXYTOLUENE	2	271,950
CHEMBL151	LUTEOLIN	2	23,845
CHEMBL150	KAEMPFEROL	1	26,246

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 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)

191 measured of 241 human assays (328 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL2079256	KI	0.8 nM
NSC_6054	KI	8 nM
CHEMBL5594635	IC50	16 nM
CHEMBL5592150	IC50	16 nM
CHEMBL5591296	IC50	16 nM
(S)-2-(5-Hydroxy-4-oxo-4H-pyran-2-ylmethoxycarbonylamino)-3-phenyl-propionic acid 5-hydroxy-4-oxo-4H-pyran-2-ylmethyl ester	IC50	60 nM
p-Coumaric Acid	IC50	140 nM
CHEBI:69084	IC50	154 nM
CHEMBL4239110	IC50	170 nM
CHEBI:69089	IC50	177 nM
3-Methoxy-xanthen-9-one	IC50	180 nM
CHEMBL5555785	IC50	220 nM
CHEMBL5542638	IC50	220 nM
CHEMBL5542520	IC50	220 nM
CHEMBL5559732	IC50	220 nM
(S)-2-[(S)-2-[(S)-2-(5-Hydroxy-4-oxo-4H-pyran-2-ylmethoxycarbonylamino)-1-oxo-3-phenyl-propylamino]-3-(1H-indol-3-yl)-propionylamino]-3-(4-hydroxy-phenyl)-propionic acid	IC50	240 nM
(1E,4E)-1,5-Bis-(4-hydroxy-3-methoxy-phenyl)-penta-1,4-dien-3-one	IC50	257 nM
1-Hydroxyxanthone	IC50	310 nM
(S)-2-{(S)-2-[(S)-2-(5-Hydroxy-4-oxo-4H-pyran-2-ylmethoxycarbonylamino)-1-oxo-3-phenyl-propylamino]-3-phenyl-propionylamino}-3-(4-hydroxy-phenyl)-propionic acid	IC50	330 nM
(S)-2-[(S)-2-[(S)-2-(5-Hydroxy-4-oxo-4H-pyran-2-ylmethoxycarbonylamino)-1-oxo-3-phenyl-propylamino]-3-(4-hydroxy-phenyl)-propionylamino]-3-(4-hydroxy-phenyl)-propionic acid	IC50	390 nM
(1E,4E)-1,5-bis(4-fluorophenyl)penta-1,4-dien-3-one	IC50	507 nM
9-oxoxanthene	IC50	623 nM
(+)-Anymol	IC50	635 nM
4-(beta-D-Cellobiopyranosyl)-2,2’,4’-trihydroxybibenzyl	IC50	680 nM
CHEMBL1794031	IC50	700 nM
4-(beta-D-Glucopyranosyl)-2,2’,4’-trihydroxybibenzyl	IC50	770 nM
(2S)-2-[(2S)-2-[(2S)-2-({[(5-hydroxy-4-oxo-4H-pyran-2-yl)methoxy]carbonyl}amino)-3-(1H-indol-3-yl)propanamido]-3-(1H-indol-3-yl)propanamido]-3-(4-hydroxyphenyl)propanoic acid	IC50	780 nM
Methyl 3-(4-Hydroxyphenyl)Acrylate	KI	780 nM
2,2’,4’-Trihydroxy-4-(beta-D-maltopyranosyl)bibenzyl	IC50	830 nM
1-Methoxy-xanthen-9-one	IC50	900 nM
4-[2-(2-pyrimidinylamino)-4-thiazolyl]benzene-1,3-diol	EC50	945 nM
CHEMBL4473314	IC50	1000 nM
SUBAMOLIDE A	IC50	1000 nM
cid_5280863	IC50	1050 nM
CHEMBL2078992	IC50	1070 nM
3-Hydroxy-xanthen-9-one	IC50	1100 nM
CHEMBL5436579	IC50	1100 nM
4-Hydroxy-xanthen-9-one	IC50	1300 nM
2-(3,4-Dihydroxy-phenyl)-5,7-dihydroxy-3-((2S,4R,5R)-3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-chromen-4-one	IC50	1320 nM
CHEMBL4763438	IC50	1400 nM
trans-2,4,3’,5’-tetramethoxystilbene	IC50	1500 nM
CHEMBL5399906	IC50	1570 nM
CHEMBL4792744	IC50	1600 nM
CHEMBL3618459	IC50	1780 nM
CHEMBL4760852	IC50	1900 nM
2,6-bis(4-hydroxybenzylidene)cyclohexanone	IC50	1940 nM
CHEMBL3618460	IC50	1980 nM
(S)-2-(5-Hydroxy-4-oxo-4H-pyran-2-ylmethoxycarbonylamino)-4-methyl-pentanoic acid 5-hydroxy-4-oxo-4H-pyran-2-ylmethyl ester	IC50	2000 nM
CHEMBL4762659	IC50	2000 nM
CHEMBL4745622	IC50	2000 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

171 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

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

Chemical	Actions (top 5)	PubMed papers
Colforsin	decreases expression, increases activity, increases expression, decreases reaction, affects cotreatment (+1 more)	4
Melanins	increases oxidation, increases reaction, affects cotreatment, decreases expression, increases abundance (+4 more)	4
Plant Extracts	decreases expression, decreases activity, affects cotreatment	3
Quercetin	increases response to substance, decreases reaction, increases activity, affects activity, affects expression (+1 more)	3
5,7-dimethoxycoumarin	affects cotreatment, increases activity, increases expression	2
caffeic acid phenethyl ester	affects response to substance, affects abundance, increases metabolic processing, increases response to substance, decreases reaction (+1 more)	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases activity, increases expression, decreases expression, decreases reaction	2
Resveratrol	affects cotreatment, decreases expression, affects localization, decreases activity	2
Copper	affects cotreatment, decreases reaction, increases expression, increases abundance, increases chemical synthesis (+2 more)	2
Valproic Acid	affects cotreatment, increases activity, increases expression	2
bisphenol F	affects cotreatment, decreases methylation	1
3,4-dihydroxyphenylpropionic acid	increases oxidation, decreases abundance	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	increases activity, decreases reaction	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	decreases abundance, increases oxidation	1
caffeic acid	decreases abundance, increases oxidation	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 299 trials:

NCT	Phase	Status	Title
NCT01955135	Phase 4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT07685886	Phase 4	NOT_YET_RECRUITING	MIRACLE-T2D Montelukast Intervention for Renal, Cardiovascular and Eye Health in Type 2 Diabetes
NCT00205881	Phase 4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	Phase 4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	Phase 4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	Phase 4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	Phase 4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	Phase 3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	Phase 3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	Phase 3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	Phase 3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00001596	Phase 2	COMPLETED	Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome
NCT01663935	Phase 2	TERMINATED	Vision Response to Dopamine Replacement
NCT01373476	Phase 2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	Phase 2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT01176435	Phase 2	COMPLETED	Trial of L-DOPA as a Treatment to Improve Vision in Albinism
NCT00013455	Phase 2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	Phase 2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	Phase 2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	Phase 2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	Phase 2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	Phase 2	WITHDRAWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	Phase 2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	Phase 2	UNKNOWN	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	Phase 2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	Phase 2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	Phase 2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	Phase 2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	Phase 1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	Phase 1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	Phase 1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	Phase 1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	Phase 1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	Phase 1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	Phase 1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	Phase 1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	Phase 1	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	Phase 1/2	TERMINATED	Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
NCT07313618	Early Phase 1	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
NCT04311112	Phase 2/3	WITHDRAWN	Safety and Efficacy of Zuretinol Acetate in Subjects With Inherited Retinal Disease
NCT04008121	Early Phase 1	RECRUITING	Feasibility and Safety of MB-102 in Ocular Angiography as Compared to Fluorescein Sodium
NCT00259701	Not specified	COMPLETED	Microvascular Reactivity.
NCT00331370	Not specified	UNKNOWN	Hypertension Related Damage to the Microcirculation in South Asian: Emergence, Predictive Power and Reversibility
NCT00618644	Not specified	WITHDRAWN	Ranibizumab for Neovascularization in Sickle Cell Retinopathy
NCT00735657	Not specified	COMPLETED	Anesthesia for Pars Plana Vitrectomy (PPV) With Insulin Needle
NCT00828425	Not specified	COMPLETED	Management of Diabetes Mellitus Patients With Retinopathy
NCT00969956	Not specified	TERMINATED	Time To Complications Occurs in Diabetes
NCT01412905	Not specified	COMPLETED	Telemedicine Retinal Screening Utilizing a Mobile Medical Unit
NCT01546766	Not specified	COMPLETED	Rapid, Non-invasive, Regional Functional Imaging of the Retina. (Diabetic Retinopathy Diagnosis Device)
NCT01552993	Not specified	TERMINATED	Registration and Treatment of Pain During Eye Examination of Prematurity
NCT01815567	Not specified	COMPLETED	DETECT and Retinal Outcomes in Hypertension
NCT02321904	Not specified	COMPLETED	Corneal Confocal Microscopy to Detect Diabetic Neuropathy in Children
NCT02466607	Not specified	COMPLETED	Study of Stimulus Parameters in Flicker Electroretinogram (ERG)
NCT02558478	Not specified	UNKNOWN	Identification of New Genes Implicated in Rare Neurosensory Diseases by Whole Exome Sequencing
NCT02702973	Not specified	UNKNOWN	Characteristic Analysis of Retinopathy Associated With High Doses of Interferon α-2b Therapy

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TYR across ~30M SureChEMBL compounds — explore on Sugi Predict.