DCT

Summary

DCT (dopachrome tautomerase, HGNC:2709) is a protein-coding gene on chromosome 13q32.1, encoding L-dopachrome tautomerase (P40126). Plays a role in melanin biosynthesis.

Predicted to enable dopachrome isomerase activity. Involved in response to blue light. Located in intracellular membrane-bounded organelle and plasma membrane. Implicated in oculocutaneous albinism.

Source: NCBI Gene 1638 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oculocutaneous albinism type 8 (Strong, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 107 total — 8 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 10
• MANE Select transcript: NM_001922

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2709
Approved symbol	DCT
Name	dopachrome tautomerase
Location	13q32.1
Locus type	gene with protein product
Status	Approved
Aliases	TRP-2, TRP2
Ensembl gene	ENSG00000080166
Ensembl biotype	protein_coding
OMIM	191275
Entrez	1638

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000377028, ENST00000446125, ENST00000472871, ENST00000483392, ENST00000490854

RefSeq mRNA: 6 — MANE Select: NM_001922 NM_001129889, NM_001322182, NM_001322184, NM_001322185, NM_001322186, NM_001922

CCDS: CCDS45060, CCDS9470

Canonical transcript exons

ENST00000377028 — 8 exons

Exon	Start	End
ENSE00000512607	94460091	94460226
ENSE00000684928	94462010	94462189
ENSE00001006902	94478961	94479682
ENSE00001250044	94468746	94469045
ENSE00001834686	94436811	94440076
ENSE00003477416	94466558	94466658
ENSE00003494913	94443436	94443637
ENSE00003598194	94465633	94465799

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 99.23.

FANTOM5 (CAGE): breadth broad, TPM avg 8.2491 / max 2771.4301, expressed in 441 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137839	6.2348	86
137846	0.7398	355
137838	0.5576	64
137837	0.1971	38
137830	0.1904	43
137833	0.1087	42
137836	0.0554	24
137834	0.0423	28
137835	0.0353	10
137831	0.0302	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	99.23	gold quality
upper arm skin	UBERON:0004263	97.54	gold quality
secondary oocyte	CL:0000655	97.18	gold quality
nipple	UBERON:0002030	96.86	gold quality
skin of hip	UBERON:0001554	96.66	gold quality
oocyte	CL:0000023	95.69	gold quality
mammalian vulva	UBERON:0000997	93.51	gold quality
penis	UBERON:0000989	93.48	gold quality
pigmented layer of retina	UBERON:0001782	88.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.10	gold quality
zone of skin	UBERON:0000014	85.30	gold quality
skin of leg	UBERON:0001511	83.49	gold quality
skin of abdomen	UBERON:0001416	83.47	gold quality
right uterine tube	UBERON:0001302	77.07	gold quality
hair follicle	UBERON:0002073	75.63	silver quality
buccal mucosa cell	CL:0002336	73.31	silver quality
pancreatic ductal cell	CL:0002079	71.86	silver quality
tibialis anterior	UBERON:0001385	69.11	silver quality
ventricular zone	UBERON:0003053	68.38	gold quality
gingiva	UBERON:0001828	68.19	gold quality
sperm	CL:0000019	67.12	silver quality
male germ cell	CL:0000015	65.84	silver quality
ileal mucosa	UBERON:0000331	64.08	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	63.06	gold quality
tongue squamous epithelium	UBERON:0006919	62.96	gold quality
pituitary gland	UBERON:0000007	62.76	gold quality
oral cavity	UBERON:0000167	62.53	gold quality
nucleus accumbens	UBERON:0001882	62.26	gold quality
adenohypophysis	UBERON:0002196	62.18	gold quality
gingival epithelium	UBERON:0001949	62.03	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-ENAD-20	yes	8617.50
E-ANND-2	yes	7684.52
E-MTAB-8142	yes	6268.22
E-MTAB-6108	yes	4679.02
E-MTAB-7407	yes	2643.70
E-MTAB-11121	yes	1268.55
E-ANND-5	yes	718.30
E-GEOD-180759	yes	195.70
E-GEOD-135922	yes	26.01
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, CTNNB1, ESR1, LEF1, MITF, NEUROD1, OTX2, PAX3, SOX10, SOX9, TCF4, TFE3

miRNA regulators (miRDB)

97 targeting DCT, 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-4795-3P	100.00	74.62	4024
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524

Literature-anchored findings (GeneRIF, showing 26)

• Data suggest that OTX2 may regulate retinal pigment epithelium (RPE)-specific target genes, such as DOPAchrome tautomerase (DCT), thereby maintaining the homeostasis of RPE. (PMID:12559959)
• Because TRP-2(181-190) overlaps with the known HLA-A*0201-presented epitope TRP-2(180-188), an 11mer peptide encompassing both epitopes might be of specific value for vaccination of a broad population of melanoma patients. (PMID:15856458)
• Transgenic Dct regulates neural progenitor cell proliferation in a mouse model. (PMID:16857183)
• No genetic susceptibility or increased risk attributed to the tyrosinase gene family in Vogt-Koyanagi-Harada disease in Japanese. (PMID:17200659)
• Anemonin, an active compound of C. crassifolia, inhibits melanin synthesis by inhibiting the transcription of the genes encoding TYR, TRP1, and TRP2. (PMID:17766092)
• we studied a possible role of dopachrome tautomerase in the oxidative stress response in the amelanotic WM35 melanoma cell line. (PMID:18206123)
• We observe strong evidence for positive selection for DCT in Asians (PMID:18312627)
• Tyrosinase-, gp100-, or TRP-2-specific CD8(+) T cells could not be identified in the peripheral blood of individuals with vitiligo [TRP-2]. (PMID:18337837)
• TRP-2 acts on quinone metabolites other than DOPAchrome, e.g., in the catecholamine pathway, and limits their deleterious effects. (PMID:18674612)
• tyrosinase-related protein 2 (TRP-2) transcript is not detected in the peripheral blood mononuclear cells (PBMC) of vitiligo patients (PMID:19284502)
• Expression profiling demonstrated that the DCT-expressing cell population expressed adrenergic and muscarinic receptors and displayed transcriptional profiles distinct from dermal melanocytes (PMID:19855129)
• Trp2 SNP2 allele is a risk factor for the development and severity of degenerative disc disease in a Chinese Han population. (PMID:20356546)
• human TRP2 counteracts apoptotic cell death induction, possibly by means of its L-dopachrome tautomerase activity, and negatively affects the p53 pathway (PMID:20520707)
• The results suggested that the miRNAs may be involved in MITF regulation of TYR, TYRP1 and TYRP2, which provides a new clue for understanding the role of miRNAs in melanocyte dysfunctional disease. (PMID:22898827)
• Data suggest that macrophage migration inhibitory factor (MIF) and d-dopachrome tautomerase (d-DT) act cooperatively to inhibit steady-state phosphorylation and activation of AMPK in LKB1 wild type and LKB1 mutant non-small cell lung carcinomas cells. (PMID:22988252)
• Report dopachrome tautomerase expression in mealanocytic tumors. (PMID:24709887)
• The effect of DCT on UVR DNA damage responses and survival pathways in melanocytes was examined by knockdown experiments using melanoma cells, neonatal melanoblasts in monoculture and in co-culture with keratinocytes. (PMID:25346513)
• Data indicate that the caveolin-1 (CAV1) control on dopachrome tautomerase (DCT) gene expression, DCT post-translational processing, and subcellular distribution is cell phenotype-dependent. (PMID:27053106)
• High DCT expression is associated with HPV16 Infection. (PMID:28095444)
• High DCT expression is associated with progressive multiple sclerosis. (PMID:28923927)
• TGF-beta and GLI2-specific TRP2 repression in melanoma cells involves direct mechanisms that occur in addition to MITF downregulation by TGF-beta and GLI2. Two functional GLI2 binding sites identified within the TRP2 promoter that are critical for TGF-beta and GLI2 responsiveness, one of them overlapping a CREB binding site. GLI2 and CREB competing for the same cis-element is associated with opposite transcriptional ou… (PMID:31208857)
• Evaluation of the effect of narrow band-ultraviolet B on the expression of tyrosinase, TYRP-1, and TYRP-2 mRNA in vitiligo skin and their correlations with clinical improvement: A retrospective study. (PMID:33314655)
• Biallelic mutations in L-dopachrome tautomerase (DCT) cause infantile nystagmus and oculocutaneous albinism. (PMID:33959807)
• Identification of TYR, TYRP1, DCT and LARP7 as related biomarkers and immune infiltration characteristics of vitiligo via comprehensive strategies. (PMID:34107850)
• Protein Biochemistry and Molecular Modeling of the Intra-Melanosomal Domain of Human Recombinant Tyrp2 Protein and OCA8-Related Mutant Variants. (PMID:35163231)
• Dopachrome tautomerase is a retinoblastoma-specific gene, and its proximal promoter is preferentially active in human retinoblastoma cells. (PMID:36274817)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dct	ENSDARG00000006008
mus_musculus	Dct	ENSMUSG00000022129
rattus_norvegicus	Dct	ENSRNOG00000008671
caenorhabditis_elegans		WBGENE00010060
caenorhabditis_elegans	tyr-4	WBGENE00016419

Paralogs (2): TYR (ENSG00000077498), TYRP1 (ENSG00000107165)

Protein

Protein identifiers

L-dopachrome tautomerase — P40126 (reviewed: P40126)

Alternative names: L-dopachrome Delta-isomerase, Tyrosinase-related protein 2

All UniProt accessions (2): P40126, A0A0A0MTD3

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in melanin biosynthesis. Catalyzes the conversion of L-dopachrome into 5,6-dihydroxyindole-2-carboxylic acid (DHICA).

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

Subcellular location. Melanosome membrane. Melanosome.

Post-translational modifications. Glycosylated.

Disease relevance. Albinism, oculocutaneous, 8 (OCA8) [MIM:619165] A form of oculocutaneous albinism, a disorder of pigmentation characterized by reduced biosynthesis of melanin in the skin, hair and eyes. OCA8 is an autosomal recessive form characterized by mild hair and skin hypopigmentation, associated with ocular features including nystagmus, reduced visual acuity, iris transillumination, and hypopigmentation of the retina. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 2 Zn(2+) ions per subunit.

Induction. Induced by blue light (415nm).

Pathway. Pigment biosynthesis; melanin biosynthesis.

Similarity. Belongs to the tyrosinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P40126-1	1	yes
P40126-2	2, TRP-2-6b

RefSeq proteins (6): NP_001123361, NP_001309111, NP_001309113, NP_001309114, NP_001309115, NP_001913* (*=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

Catalyzed reactions (Rhea), 1 shown:

• L-dopachrome = 5,6-dihydroxyindole-2-carboxylate (RHEA:13041)

UniProt features (20 total): binding site 6, glycosylation site 6, sequence variant 2, topological domain 2, signal peptide 1, chain 1, splice variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4HX1	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40126-F1	89.33	0.82

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): 396; 189; 211; 220; 369; 373

Glycosylation sites (6): 170, 178, 237, 300, 342, 377

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: 198 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, YAATNRNNNYNATT_UNKNOWN, MYOGENIN_Q6, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_NEUROGENESIS, MODULE_335, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, RIZKI_TUMOR_INVASIVENESS_3D_DN, LHX3_01, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_CELL_PROLIFERATION_IN_FOREBRAIN, GOBP_POSITIVE_REGULATION_OF_NEUROBLAST_PROLIFERATION

GO Biological Process (10): positive regulation of neuroblast proliferation (GO:0002052), melanin biosynthetic process from tyrosine (GO:0006583), epidermis development (GO:0008544), response to blue light (GO:0009637), ventricular zone neuroblast division (GO:0021847), developmental pigmentation (GO:0048066), cell development (GO:0048468), neuroblast proliferation (GO:0007405), melanin biosynthetic process (GO:0042438), pigmentation (GO:0043473)

GO Molecular Function (6): dopachrome isomerase activity (GO:0004167), copper ion binding (GO:0005507), oxidoreductase activity (GO:0016491), protein binding (GO:0005515), isomerase activity (GO:0016853), metal ion binding (GO:0046872)

GO Cellular Component (7): cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), melanosome membrane (GO:0033162), melanosome (GO:0042470), cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410)

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
catalytic activity	2
cytoplasm	2
neuroblast proliferation	1
positive regulation of neurogenesis	1
regulation of neuroblast proliferation	1
positive regulation of neural precursor cell proliferation	1
melanin biosynthetic process	1
tissue development	1
response to light stimulus	1
forebrain ventricular zone progenitor cell division	1
forebrain neuroblast division	1
pigmentation	1
cell differentiation	1
anatomical structure development	1
cellular developmental process	1
generation of neurons	1
neural precursor cell proliferation	1
melanin metabolic process	1
secondary metabolite biosynthetic process	1
pigment biosynthetic process	1
phenol-containing compound biosynthetic process	1
biological_process	1
intramolecular oxidoreductase activity, transposing C=C bonds	1
transition metal ion binding	1
binding	1
cation binding	1
membrane	1
cell periphery	1
melanosome	1
chitosome	1
pigment granule membrane	1
pigment granule	1
intracellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

1657 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCT	MITF	O75030	951
DCT	SOX10	P56693	829
DCT	TYR	P14679	797
DCT	PMEL	P40967	789
DCT	POMC	P01189	756
DCT	MC1R	Q01726	752
DCT	PAX3	P23760	740
DCT	HSPA4	P34932	737
DCT	DDT	P30046	696
DCT	GPR143	P51810	663
DCT	GRM1	Q13255	661
DCT	ASIP	P42127	661
DCT	MLANA	Q16655	660
DCT	RAB27A	P51159	660
DCT	SLC45A2	Q9UMX9	645

IntAct

7 interactions, top by confidence:

A	B	Type	Score
DCT	PLP1	psi-mi:“MI:0915”(physical association)	0.560
DCT	CANX	psi-mi:“MI:0914”(association)	0.530
PLP1	DCT	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): PLXNA4 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), EDEM2 (Affinity Capture-MS), TXNDC11 (Affinity Capture-MS), CANX (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), LGR4 (Affinity Capture-MS), PLP1 (Two-hybrid), DCT (Affinity Capture-MS), PRKAA2 (Affinity Capture-MS), CANX (Affinity Capture-MS), DPP9 (Affinity Capture-MS), PLXNA4 (Affinity Capture-MS), ALG11 (Affinity Capture-MS), EDEM2 (Affinity Capture-MS)

ESM2 similar proteins: A0A142I737, A0A336U966, A0A3B1EFP7, A0A443HK52, A0A8J9R8H5, A0A8J9RRY2, A1CMH6, A1DDD8, A1DLJ5, A2Q7V4, A7BHQ9, A8C7R9, A8NYP0, B0XPZ1, B8NM74, B8NMK3, C7FF04, C7FF05, D4AR77, D4AV38, L0E2Q5, O42713, O93505, P00440, P07147, P0DUQ0, P12031, P17643, P29812, P40126, P56823, P56825, P56826, P80960, P81732, P83040, Q00024, Q0CRX0, Q10584, Q2U1N5

Diamond homologs: O57405, O93505, P07147, P11344, P14679, P17643, P29812, P40126, P54834, P55024, P55025, P55026, P55027, P55028, P55033, Q04604, Q08410, Q0MVP0, Q2VPW6, Q4R1H1, Q8MIU0, Q8WN57, Q95119, Q9BDE0, B1VTI5, P06845, P55023, A0A142I737, A0A261GVB1, A0A8J9R8H5, A0A8J9RRY2, B8NM74, H2A0L0, H2A0L1, P07524, P12659, P33180, P55022, P86952, Q00234

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MITF	“up-regulates quantity by expression”	DCT	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	2
Uncertain significance	82
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1268230	NM_001922.5(DCT):c.176G>T (p.Gly59Val)	Pathogenic
1268231	NM_001922.5(DCT):c.876C>A (p.Tyr292Ter)	Pathogenic
1268232	NM_001922.5(DCT):c.1407G>A (p.Trp469Ter)	Pathogenic
2425401	NC_000013.10:g.(?93879710)(95248390_?)del	Pathogenic
2685478	GRCh37/hg19 13q31.2-33.2(chr13:89012420-106371634)x1	Pathogenic
3233659	NM_001922.5(DCT):c.212G>A (p.Trp71Ter)	Pathogenic
4819284	NM_001922.5(DCT):c.976C>T (p.Arg326Ter)	Pathogenic
57644	GRCh38/hg38 13q22.3-32.1(chr13:78349126-94701844)x1	Pathogenic
2497715	NM_001922.5(DCT):c.386A>T (p.Asn129Ile)	Likely pathogenic
3893090	NM_001922.5(DCT):c.555dup (p.Val186fs)	Likely pathogenic

SpliceAI

1205 predictions. Top by Δscore:

Variant	Effect	Δscore
13:94443431:GTTA:G	donor_loss	1.0000
13:94443433:TA:T	donor_loss	1.0000
13:94443435:C:G	donor_loss	1.0000
13:94443634:GAACC:G	acceptor_loss	1.0000
13:94443636:ACC:A	acceptor_loss	1.0000
13:94443637:CCT:C	acceptor_loss	1.0000
13:94443638:C:A	acceptor_loss	1.0000
13:94443639:T:A	acceptor_loss	1.0000
13:94460222:CATTC:C	acceptor_gain	1.0000
13:94462197:T:TC	acceptor_gain	1.0000
13:94465763:A:T	acceptor_gain	1.0000
13:94466553:CCTA:C	donor_loss	1.0000
13:94466554:CTAC:C	donor_loss	1.0000
13:94466556:ACC:A	donor_loss	1.0000
13:94466557:C:A	donor_loss	1.0000
13:94466659:C:CC	acceptor_gain	1.0000
13:94466665:C:CT	acceptor_gain	1.0000
13:94468815:A:AC	donor_gain	1.0000
13:94468816:C:CC	donor_gain	1.0000
13:94468931:T:A	donor_gain	1.0000
13:94443435:CCTGG:C	donor_gain	0.9900
13:94443455:G:C	donor_gain	0.9900
13:94443633:AGAAC:A	acceptor_gain	0.9900
13:94443634:GAAC:G	acceptor_gain	0.9900
13:94443636:AC:A	acceptor_gain	0.9900
13:94443637:CC:C	acceptor_gain	0.9900
13:94443638:C:CC	acceptor_gain	0.9900
13:94443646:CAGT:C	acceptor_gain	0.9900
13:94460084:AACAT:A	donor_loss	0.9900
13:94460085:ACATA:A	donor_loss	0.9900

AlphaMissense

3415 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:94479009:G:T	R83S	0.997
13:94466599:A:G	W219R	0.996
13:94466599:A:T	W219R	0.996
13:94466597:C:A	W219C	0.995
13:94466597:C:G	W219C	0.995
13:94478998:C:A	W86C	0.995
13:94478998:C:G	W86C	0.995
13:94466592:C:G	R221P	0.994
13:94479008:C:G	R83P	0.994
13:94479015:C:G	D81H	0.992
13:94465639:C:G	C286S	0.991
13:94465640:A:T	C286S	0.991
13:94465650:C:A	W282C	0.991
13:94465650:C:G	W282C	0.991
13:94466562:A:G	L231P	0.991
13:94468894:C:A	K149N	0.991
13:94468894:C:G	K149N	0.991
13:94479000:A:G	W86R	0.991
13:94479000:A:T	W86R	0.991
13:94462015:A:C	S346R	0.990
13:94462015:A:T	S346R	0.990
13:94462017:T:G	S346R	0.990
13:94462157:C:G	C299S	0.990
13:94462158:A:T	C299S	0.990
13:94465763:A:G	W245R	0.989
13:94465763:A:T	W245R	0.989
13:94460094:A:C	F392L	0.988
13:94460094:A:T	F392L	0.988
13:94460096:A:G	F392L	0.988
13:94460104:T:C	D389G	0.988

dbSNP variants (sampled 300 via entrez): RS1000022877 (13:94479743 G>A), RS1000060638 (13:94450597 G>A,T), RS1000082468 (13:94528080 G>T), RS1000112866 (13:94517316 C>A,T), RS1000192577 (13:94515035 A>G), RS1000194973 (13:94517304 C>T), RS1000201673 (13:94468195 A>C), RS1000227500 (13:94517779 C>T), RS1000252531 (13:94468421 T>G), RS1000264431 (13:94523303 G>A), RS1000303420 (13:94467504 A>C), RS1000312310 (13:94533679 G>C), RS1000341489 (13:94437087 G>C), RS1000347609 (13:94511640 G>A), RS1000412109 (13:94450328 T>A)

Disease associations

OMIM: gene MIM:191275 | disease phenotypes: MIM:619165, MIM:610149

GenCC curated gene-disease

Disease	Classification	Inheritance
oculocutaneous albinism type 8	Strong	Autosomal recessive

Mondo (3): oculocutaneous albinism type 8 (MONDO:0030899), age related macular degeneration 7 (MONDO:0012419), albinism (MONDO:0043209)

Orphanet (1): Oculocutaneous albinism type 8 (Orphanet:597733)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0001010	Hypopigmentation of the skin
HP:0003577	Congenital onset
HP:0005599	Hypopigmentation of hair
HP:0007663	Reduced visual acuity
HP:0007750	Hypoplasia of the fovea
HP:0012805	Iris transillumination defect
HP:0040030	Chorioretinal hypopigmentation

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003226_18	Pelvic organ prolapse	6.000000e-06
GCST003542_155	Night sleep phenotypes	7.000000e-06
GCST005897_42	Low tan response	1.000000e-09
GCST006075_17	Hair color	6.000000e-68
GCST006988_160	Blond vs. brown/black hair color	3.000000e-92

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004279	suntan
EFO:0003924	hair color

MeSH disease descriptors (2)

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
C565718	Macular Degeneration, Age-Related, 7 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	2
Colforsin	increases expression	2
Nickel	decreases expression	2
Genistein	decreases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
amentoflavone	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	decreases reaction, decreases expression	1
sodium arsenite	increases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
artemisic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
SB 203580	decreases reaction, increases expression	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases expression, decreases reaction	1
2-palmitoylglycerol	increases expression	1
cyclohexyl-(2-(3,5-dimethylpyrazol-1-yl)-6-methylpyrimidin-4-yl)amine	decreases expression	1
Resveratrol	decreases expression	1
Temozolomide	decreases response to substance	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Acetylglucosamine	increases expression	1
Caffeine	increases expression	1
Cannabidiol	decreases reaction, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	affects expression	1
Emodin	decreases expression	1
Etoposide	affects response to substance	1
Fluorouracil	affects expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0W8	SEES3-1V human DCT, clone1	Embryonic stem cell	Male
CVCL_A0W9	SEES3-1V human DCT, clone2	Embryonic stem cell	Male
CVCL_A0X0	SEES3-1V human DCT, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001596	PHASE2	COMPLETED	Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome
NCT01176435	PHASE2	COMPLETED	Trial of L-DOPA as a Treatment to Improve Vision in Albinism
NCT01663935	PHASE2	TERMINATED	Vision Response to Dopamine Replacement
NCT01838655	PHASE1/PHASE2	COMPLETED	Nitisinone for Type 1B Oculocutaneous Albinism
NCT00001153	Not specified	COMPLETED	Visual Function and Ocular Pigmentation in Albinism
NCT04281732	Not specified	UNKNOWN	Visual Performance Measures in a Virtual Reality Environment for Assessing Clinical Trial Outcomes in Those With Severely Reduced Vision
NCT04658381	Not specified	COMPLETED	Genetic Analysis and Multimodal Retinal Imaging of Asymptomatic Fovea Plana Cases in the General Population
NCT05696912	Not specified	UNKNOWN	Functional Tests to Resolve Unsolved Rare Diseases. Rares.
NCT05954416	Not specified	RECRUITING	FARD (RaDiCo Cohort) (RaDiCo-FARD)
NCT06330324	Not specified	ENROLLING_BY_INVITATION	Reproductive Options in Inherited Skin Diseases
NCT06330350	Not specified	RECRUITING	Qualitative Study in Patients With Genodermatoses and Healthcare Professionals on Reproductive Counselling
NCT06491615	Not specified	RECRUITING	National Ophthalmic Genotyping and Phenotyping Network (eyeGENE (Registered Trademark)), Stage 3 - Expansion of DNA and Data Repositories for Rare Inherited Ophthalmic Diseases
NCT07400913	Not specified	NOT_YET_RECRUITING	Implementation of Long-read Sequencing for the Diagnosis of Rare Diseases.