oculocutaneous albinism type 1B

Summary

oculocutaneous albinism type 1B (MONDO:0011749) is a disease caused by TYR (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Causal gene: TYR (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 164
• Phenotypes (HPO): 17

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1.3	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0000486	Strabismus	Very frequent (80-99%)
HP:0001010	Hypopigmentation of the skin	Very frequent (80-99%)
HP:0001022	Albinism	Very frequent (80-99%)
HP:0001480	Freckling	Very frequent (80-99%)
HP:0005599	Hypopigmentation of hair	Very frequent (80-99%)
HP:0007703	Abnormality of retinal pigmentation	Very frequent (80-99%)
HP:0007730	Iris hypopigmentation	Very frequent (80-99%)
HP:0000505	Visual impairment	Frequent (30-79%)
HP:0000587	Abnormal optic nerve morphology	Frequent (30-79%)
HP:0000613	Photophobia	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0000995	Melanocytic nevus	Frequent (30-79%)
HP:0007750	Hypoplasia of the fovea	Frequent (30-79%)
HP:0001072	Thickened skin	Occasional (5-29%)
HP:0002671	Basal cell carcinoma	Occasional (5-29%)
HP:0002861	Melanoma	Occasional (5-29%)
HP:0006739	Squamous cell carcinoma of the skin	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	oculocutaneous albinism type 1B
Mondo ID	MONDO:0011749
MeSH	C537729
OMIM	606952
Orphanet	79434
DOID	DOID:0070095
ICD-11	1233842528
UMLS	C1847024
MedGen	337712
GARD	0000594
Is cancer (heuristic)	no

Also known as: albinism, oculocutaneous, type IB · albinism, Yellow mutant type · OCA1B · oculocutaneous albinism, Amish type · platinum oculocutaneous albinism · Yellow mutant albinism · Yellow oculocutaneous albinism

Data availability: 164 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: 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 › inborn disorder of phenylalanine and tyrosine metabolism › disorder of tyrosine metabolism › oculocutaneous albinism type 1 › oculocutaneous albinism type 1A › oculocutaneous albinism type 1B

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

164 retrieved; paginated sample, class counts are floors:

54 pathogenic/likely pathogenic, 34 pathogenic, 33 likely pathogenic, 21 conflicting classifications of pathogenicity, 18 uncertain significance, 2 likely benign, 1 not provided, 1 conflicting classifications of pathogenicity; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
1027642	NM_000372.5(TYR):c.1056del (p.Gly353_Ile354insTer)	TYR	Pathogenic	criteria provided, single submitter
1175803	NM_000372.5(TYR):c.1036+1G>A	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1180809	NM_000372.5(TYR):c.996G>A (p.Met332Ile)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1381832	NM_000372.5(TYR):c.1366+1G>T	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1390436	NM_000372.5(TYR):c.71G>A (p.Cys24Tyr)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
1438386	NM_000372.5(TYR):c.773_774del (p.Thr258fs)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
144105	NM_000372.5(TYR):c.551C>G (p.Ser184Ter)	TYR	Pathogenic	criteria provided, single submitter
144106	NM_000372.5(TYR):c.739T>C (p.Cys247Arg)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1442280	NM_000372.5(TYR):c.290G>T (p.Gly97Val)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453014	NM_000372.5(TYR):c.216del (p.Val74fs)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
1455534	NM_000372.5(TYR):c.626C>T (p.Pro209Leu)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458009	NM_000372.5(TYR):c.862_863del (p.Leu288fs)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458014	NM_000372.5(TYR):c.1106A>G (p.Tyr369Cys)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458819	NM_000372.5(TYR):c.606T>G (p.His202Gln)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1699463	NM_000372.5(TYR):c.1237del (p.Glu413fs)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
190217	NM_000372.5(TYR):c.902C>T (p.Pro301Leu)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
212522	NM_000372.5(TYR):c.446A>G (p.Tyr149Cys)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
212524	NM_000372.5(TYR):c.661G>A (p.Glu221Lys)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2137224	NM_000372.5(TYR):c.229C>G (p.Arg77Gly)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
2137228	NM_000372.5(TYR):c.593T>C (p.Ile198Thr)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2137234	NM_000372.5(TYR):c.1037-3C>G	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2501774	NM_000372.5(TYR):c.1322del (p.Ser441fs)	TYR	Pathogenic	criteria provided, single submitter
2679405	NM_000372.5(TYR):c.1045_1046insAT (p.Ser349fs)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2679408	NM_000372.5(TYR):c.241C>T (p.Pro81Ser)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2679413	NM_000372.5(TYR):c.440C>G (p.Ser147Ter)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2735722	NM_000372.5(TYR):c.425A>T (p.Lys142Met)	TYR	Pathogenic	criteria provided, multiple submitters, no conflicts
2735734	NM_000372.5(TYR):c.1200G>T (p.Trp400Cys)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2899498	NM_000372.5(TYR):c.1322C>A (p.Ser441Ter)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2989319	NM_000372.5(TYR):c.838G>T (p.Glu280Ter)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3000471	NM_000372.5(TYR):c.696del (p.Ile233fs)	TYR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 5 · 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
TYR	Definitive	Autosomal recessive	oculocutaneous albinism type 1A	10

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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TYR	HGNC:12442	ENSG00000077498	P14679	Tyrosinase	gencc,clinvar
ZDHHC15	HGNC:20342	ENSG00000102383	Q96MV8	Palmitoyltransferase ZDHHC15	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TYR	Tyrosinase	This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds.
ZDHHC15	Palmitoyltransferase ZDHHC15	Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TYR	Enzyme (other)	yes	1.14.18.1	Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
ZDHHC15	Other/Unknown	no		Palmitoyltrfase_DHHC, PFA4/ZDH16/20/ERF2-like

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
pigmented layer of retina	1
upper leg skin	1
ganglionic eminence	1
primordial germ cell in gonad	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TYR	59	tissue_specific	marker	pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis, upper leg skin
ZDHHC15	168	broad	yes	primordial germ cell in gonad, ventricular zone, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TYR	3,663
ZDHHC15	919

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TYR	P14679	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZDHHC15	Q96MV8	89.20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Melanin biosynthesis	1	2284.0×	9e-04	TYR
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.004	TYR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein localization to postsynapse	1	8426.0×	0.002	ZDHHC15
eye pigment biosynthetic process	1	4213.0×	0.002	TYR
protein targeting to Golgi apparatus	1	2808.7×	0.002	ZDHHC15
melanin biosynthetic process from tyrosine	1	2106.5×	0.002	TYR
response to blue light	1	1685.2×	0.002	TYR
synaptic vesicle maturation	1	936.2×	0.003	ZDHHC15
melanin biosynthetic process	1	648.1×	0.004	TYR
peptidyl-L-cysteine S-palmitoylation	1	601.9×	0.004	ZDHHC15
positive regulation of dendrite development	1	495.6×	0.004	ZDHHC15
regulation of dendritic spine morphogenesis	1	421.3×	0.004	ZDHHC15
response to vitamin D	1	401.2×	0.004	TYR
pigmentation	1	351.1×	0.005	TYR
protein localization to membrane	1	300.9×	0.005	ZDHHC15
response to cAMP	1	255.3×	0.005	TYR
response to UV	1	183.2×	0.007	TYR
thymus development	1	168.5×	0.007	TYR
protein targeting to membrane	1	147.8×	0.008	ZDHHC15
cell population proliferation	1	51.4×	0.020	TYR
visual perception	1	39.8×	0.025	TYR

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
ZDHHC15	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

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: 2; 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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ZDHHC15

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ZDHHC15	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.