Albinism

Summary

Albinism (MONDO:0043209) is a disease with 7 cohort genes and 13 clinical trials. The dominant Reactome pathway is Melanin biosynthesis (3 cohort genes). Top therapeutic interventions include carbidopa anhydrous, levodopa, and nitisinone.

At a glance

• Cohort genes: 7
• ClinVar variants: 21
• Clinical trials: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	albinism
Mondo ID	MONDO:0043209
MeSH	D000417
ICD-10-CM	E70.3
NCIT	C84543
SNOMED CT	15890002
UMLS	C0001916
MedGen	182
Is cancer (heuristic)	no

Also known as: albinism

Data availability: 21 ClinVar variants · 1 GenCC gene-disease record · 2 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of amino acid metabolism › albinism

Related subtypes (32): disorder of methionine catabolism, inborn serine deficiency, cerebral creatine deficiency syndrome, inborn organic aciduria, gamma-amino butyric acid metabolism disorder, homocystinuria, urea cycle disorder, adenylosuccinate lyase deficiency, systemic primary carnitine deficiency disease, cystathioninuria, hyperlysinemia, Brunner syndrome, glycine encephalopathy, aminoacylase 1 deficiency, adenine phosphoribosyltransferase deficiency, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, inborn disorder of tryptophan metabolism, inborn disorder of proline metabolism, inborn disorder of ornithine metabolism, inborn disorder of amino acid transport, inborn disorder of histidine metabolism, inborn disorder of phenylalanine and tyrosine metabolism, inborn disorder of branched-chain amino acid metabolism, arakawa syndrome 2, 2-methylacetoacetyl CoA thiolase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, inborn disorder of the metabolism of sulfur-containing amino acids and hydrogen sulfide, inborn disorder of glycine and serine metabolism, inborn disorder of ornithine, proline and hydroxyproline metabolism, inborn disorder of glutamate/glutamine and aspartate/asparagine metabolism, hyperglycinemia, transient neonatal, tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia

Subtypes (2): albinism-hearing loss syndrome, X-linked recessive ocular albinism

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

21 retrieved; paginated sample, class counts are floors:

11 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 3 likely pathogenic, 2 pathogenic, 1 conflicting classifications of pathogenicity; other, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
929863	NM_001922.5(DCT):c.118T>A (p.Cys40Ser)	DCT	Pathogenic/Likely pathogenic	no assertion criteria provided
929864	NM_001922.5(DCT):c.183C>G (p.Cys61Trp)	DCT	Pathogenic/Likely pathogenic	no assertion criteria provided
930182	NM_001922.5(DCT):c.1307_1320del (p.Phe435_Phe436insTer)	DCT	Pathogenic/Likely pathogenic	no assertion criteria provided
98647	NM_000273.3(GPR143):c.874T>G (p.Trp292Gly)	GPR143	Pathogenic	criteria provided, multiple submitters, no conflicts
17593	NM_000550.3(TYRP1):c.1103del (p.Lys368fs)	LURAP1L-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
437186	NM_000550.3(TYRP1):c.1261+1G>A	LURAP1L-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
436090	NM_000275.3(OCA2):c.2339G>A (p.Gly780Asp)	OCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3772	NM_000372.5(TYR):c.242C>T (p.Pro81Leu)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
3781	NM_000372.5(TYR):c.265T>C (p.Cys89Arg)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3807	NM_000372.5(TYR):c.1A>G (p.Met1Val)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
437987	NM_000372.5(TYR):c.1264C>T (p.Arg422Trp)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99527	NM_000372.5(TYR):c.1037-7T>A	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
99562	NM_000372.5(TYR):c.325G>A (p.Gly109Arg)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
438187	NM_000273.3(GPR143):c.779A>G (p.Asn260Ser)	GPR143	Likely pathogenic	no assertion criteria provided
438059	NM_000275.3(OCA2):c.1660T>C (p.Trp554Arg)	OCA2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
438247	NM_000275.3(OCA2):c.646+1825_807+679del	OCA2	Likely pathogenic	no assertion criteria provided
373910	NM_000275.3(OCA2):c.1025A>G (p.Tyr342Cys)	OCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3779	NM_000372.5(TYR):c.1205G>A (p.Arg402Gln)	TYR	Conflicting classifications of pathogenicity; other	criteria provided, conflicting classifications
523363	NM_000372.5(TYR):c.1352A>G (p.Tyr451Cys)	TYR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
99528	NM_000372.5(TYR):c.1063G>C (p.Ala355Pro)	TYR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
523490	NM_001354768.3(NRL):c.448_466dup (p.Glu156fs)	NRL	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TPCN2	Limited	Autosomal dominant	albinism

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TYR	Orphanet:352734	Minimal pigment oculocutaneous albinism type 1
TYR	Orphanet:352737	Temperature-sensitive oculocutaneous albinism type 1
TYR	Orphanet:79431	Oculocutaneous albinism type 1A
TYR	Orphanet:79434	Oculocutaneous albinism type 1B
TYR	Orphanet:895	Waardenburg syndrome type 2
GPR143	Orphanet:54	X-linked recessive ocular albinism
DCT	Orphanet:597733	Oculocutaneous albinism type 8
NRL	Orphanet:791	Retinitis pigmentosa
OCA2	Orphanet:177901	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1
OCA2	Orphanet:177904	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2
OCA2	Orphanet:79432	Oculocutaneous albinism type 2
OCA2	Orphanet:98754	Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15
OCA2	Orphanet:98794	Angelman syndrome due to maternal 15q11q13 deletion

Cohort genes → proteins

7 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TPCN2	HGNC:20820	ENSG00000162341	Q8NHX9	Two pore channel protein 2	gencc
TYR	HGNC:12442	ENSG00000077498	P14679	Tyrosinase	clinvar
GPR143	HGNC:20145	ENSG00000101850	P51810	G-protein coupled receptor 143	clinvar
DCT	HGNC:2709	ENSG00000080166	P40126	L-dopachrome tautomerase	clinvar
LURAP1L-AS1	HGNC:49761	ENSG00000235448		LURAP1L antisense RNA 1	clinvar
NRL	HGNC:8002	ENSG00000129535	P54845	Neural retina-specific leucine zipper protein	clinvar
OCA2	HGNC:8101	ENSG00000104044	Q04671	P protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TPCN2	Two pore channel protein 2	Intracellular channel initially characterized as a non-selective Ca(2+)-permeable channel activated by NAADP (nicotinic acid adenine dinucleotide phosphate), it is also a highly-selective Na(+) channel activated directly by PI(3,5)P2 (phos…
TYR	Tyrosinase	This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds.
GPR143	G-protein coupled receptor 143	Receptor for tyrosine, L-DOPA and dopamine.
DCT	L-dopachrome tautomerase	Plays a role in melanin biosynthesis.
NRL	Neural retina-specific leucine zipper protein	Acts as a transcriptional activator which regulates the expression of several rod-specific genes, including RHO and PDE6B.
OCA2	P protein	Contributes to a melanosome-specific anion (chloride) current that modulates melanosomal pH for optimal tyrosinase activity required for melanogenesis and the melanosome maturation.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.43

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	2	31.9×	0.007
Enzyme (other)	1	1.7×	0.793
Transcription factor	1	1.2×	0.793
Other/Unknown	3	0.8×	0.858

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TPCN2	Ion channel	yes		Ion_trans_dom, Volt_channel_dom_sf, TPC2
TYR	Enzyme (other)	yes	1.14.18.1	Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
GPR143	Other/Unknown	no		GPR143
DCT	Other/Unknown	no		Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
LURAP1L-AS1	Other/Unknown	no
NRL	Transcription factor	no		bZIP_Maf, bZIP, TF_DNA-bd_sf
OCA2	Ion channel	yes		Cit_transptr-like_dom, Diverse_Ion_Transporter

Expression context

Cohort genes with no expression data: 0.

6 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	3
pigmented layer of retina	3
secondary oocyte	3
upper leg skin	2
ileal mucosa	1
kidney epithelium	1
pancreatic ductal cell	1
oocyte	1
upper arm skin	1
adrenal tissue	1
sural nerve	1
cortical plate	1
hindlimb stylopod muscle	1
choroid plexus epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TPCN2	236	ubiquitous	marker	pancreatic ductal cell, kidney epithelium, ileal mucosa
TYR	59	tissue_specific	marker	pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis, upper leg skin
GPR143	170	broad	marker	oocyte, secondary oocyte, pigmented layer of retina
DCT	184	broad	marker	upper leg skin, upper arm skin, secondary oocyte
LURAP1L-AS1	151	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, sural nerve, adrenal tissue
NRL	129	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle, cortical plate
OCA2	192	tissue_specific	marker	pigmented layer of retina, choroid plexus epithelium, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 7.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TYR	3,663
OCA2	2,132
GPR143	1,871
DCT	1,692
TPCN2	1,436
NRL	937
LURAP1L-AS1	0

Intra-cohort edges

A	B	Sources
DCT	GPR143	string_interaction
DCT	TYR	string_interaction
GPR143	OCA2	string_interaction
GPR143	TYR	intact, string_interaction
OCA2	TPCN2	string_interaction
OCA2	TYR	string_interaction
TPCN2	TYR	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 3 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TPCN2	Q8NHX9	4
TYR	P14679	1
DCT	P40126	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GPR143	P51810	74.37
OCA2	Q04671	73.79
NRL	P54845	72.42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 7 evidence-associated genes (5 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Melanin biosynthesis	3	1370.4×	2e-09	TYR, DCT, OCA2
Regulation of MITF-M-dependent genes involved in pigmentation	3	159.3×	1e-06	TYR, GPR143, DCT
Amine ligand-binding receptors	1	69.2×	0.024	GPR143
Stimuli-sensing channels	1	27.2×	0.045	TPCN2
G alpha (q) signalling events	1	11.5×	0.084	GPR143

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
melanin biosynthetic process from tyrosine	3	2106.5×	5e-09	TYR, DCT, OCA2
eye pigment biosynthetic process	2	2808.7×	2e-06	TYR, GPR143
response to blue light	2	1123.5×	2e-05	TYR, DCT
melanin biosynthetic process	2	432.1×	9e-05	TYR, OCA2
response to vitamin D	2	267.5×	2e-04	TYR, TPCN2
visual perception	3	39.8×	3e-04	TYR, GPR143, NRL
negative regulation of developmental pigmentation	1	2808.7×	0.002	TPCN2
regulation of melanosome transport	1	2808.7×	0.002	GPR143
endosome to lysosome transport of low-density lipoprotein particle	1	1404.3×	0.003	TPCN2
regulation of melanosome organization	1	1404.3×	0.003	GPR143
endocytosis involved in viral entry into host cell	1	936.2×	0.004	TPCN2
ventricular zone neuroblast division	1	702.2×	0.005	DCT
cell population proliferation	2	34.2×	0.005	TYR, OCA2
melanosome localization	1	561.7×	0.005	GPR143
lysosomal lumen pH elevation	1	561.7×	0.005	OCA2
developmental pigmentation	1	351.1×	0.008	DCT
retinal rod cell development	1	280.9×	0.009	NRL
receptor-mediated endocytosis of virus by host cell	1	255.3×	0.010	TPCN2
intracellular pH reduction	1	200.6×	0.012	TPCN2
cell development	1	147.8×	0.015	DCT
smooth muscle contraction	1	133.8×	0.015	TPCN2
melanocyte differentiation	1	133.8×	0.015	OCA2
melanosome transport	1	127.7×	0.015	GPR143
regulation of exocytosis	1	117.0×	0.015	TPCN2
pigmentation	1	117.0×	0.015	TYR
melanosome organization	1	108.0×	0.016	GPR143
positive regulation of neuroblast proliferation	1	96.8×	0.017	DCT
response to cAMP	1	85.1×	0.019	TYR
response to UV	1	61.1×	0.025	TYR
release of sequestered calcium ion into cytosol	1	57.3×	0.026	TPCN2

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Levodopa.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 6

Druggability breadth: 2 of 7 evidence-associated genes (29%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TYR	ASCORBIC ACID

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TYR	10	4
TPCN2	0	0
GPR143	0	0
DCT	0	0
LURAP1L-AS1	0	0
NRL	0	0
OCA2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ASCORBIC ACID	4	TYR
HEXYLRESORCINOL	4	TYR
HYDROQUINONE	4	TYR
CURCUMIN	3	TYR
RESVERATROL	3	TYR
QUERCETIN	3	TYR
BUTYLATED HYDROXYTOLUENE	2	TYR
LUTEOLIN	2	TYR
ARBUTIN	2	TYR
KAEMPFEROL	1	TYR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TYR	211	Binding:209, ADMET:2
GPR143	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TYR	1.14.18.1	tyrosinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TYR	211

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

10 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
ASCORBIC ACID	4	TYR
HEXYLRESORCINOL	4	TYR
HYDROQUINONE	4	TYR
CURCUMIN	3	TYR
RESVERATROL	3	TYR
QUERCETIN	3	TYR
BUTYLATED HYDROXYTOLUENE	2	TYR
LUTEOLIN	2	TYR
ARBUTIN	2	TYR
KAEMPFEROL	1	TYR

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TYR
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	TPCN2
D	Druggable family + AlphaFold only, no drug	1	OCA2
E	Difficult family or no structure, no drug	4	GPR143, DCT, LURAP1L-AS1, NRL

Undrugged target profiles

6 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GPR143	3	TYR
DCT	0	TYR
OCA2	0	TYR
TPCN2	0	—
LURAP1L-AS1	0	—
NRL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 13.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	9
PHASE2	3
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	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
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.
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.

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CARBIDOPA ANHYDROUS	4	3
LEVODOPA	4	2
NITISINONE	4	1
PIRFENIDONE	4	1
CHEMBL351042	0	2
CHEMBL23996	0	1