Albinism: Genetics


Albinism is a reduction of pigment production in the skin, hair and eyes, plus a variable but characteristic change in eye development. Pigmentation research has shown that albinism is a complex genetic disorder, involving many genes with an array of functions, producing a wide phenotypic spectrum amongst affected individuals. There are currently 24 genetic disorders that have albinism included with the phenotype, including as many as 7 nonsyndromic forms of oculocutaneous albinism (reduced pigment affects skin, hair and eyes), 1 nonsyndromic form of ocular albinism (reduced pigment affects eyes only) and 16 syndromic disorders. The gene functions of the nonsyndromic forms are thought to be involved in melanin biosynthesis and many of the genes associated with the syndromic forms are involved in protein trafficking and vesicular function. Common genetic variants within some of these genes are also associated with normal variation in eye, hair and skin colouration.

Key Concepts

  • All animals make melanin as the chief form of colouration.
  • Melanin is made in specific cells called melanocytes.
  • Albinism is caused by a reduction or absence of melanin biosynthesis resulting in several clinical features.
  • There are many different types of albinism.
  • There are several genes associated with albinism.
  • The molecular pathology of albinism is complex and involves different pathways and different types of mutations.
  • Variation in skin pigmentation involves common polymorphisms in some albinism related genes.
  • Albinism can affect interactions between individuals and society.

Keywords: oculocutaneous albinism; tyrosinase; nystagmus; melanin; pigmentation

Figure 1. Melanin pathway. The initial substrate for melanin biosynthesis is the amino acid tyrosine. The rate‐limiting enzyme is tyrosinase (TYR), which has both tyrosine hydroxylase and dopa oxidase activity. In the presence of sulfhydral‐containing compounds, such as cysteine, pheomelanin is produced through the compound cysteinyldopa. In the absence of sulfhydral groups, black‐brown eumelanin is synthesized. Two other enzymes are involved in the eumelanin pathway, dopachrome tautomerase (TYRP2), and dihydroxyindolecarboxylic acid (DHICA) oxidase (TYRP1).
Figure 2. Structure of tyrosinase. Tyrosinase is a copper‐containing enzyme and the rate‐limiting enzyme in melanin biosynthesis. This figure shows the coding region of the TYR gene (529 amino acids). The signal peptide is important in protein trafficking and translation on membrane‐bound ribosomes. The boxes shown as CuA and CuB are the two copper binding regions. The circles show the location of cysteine residues and the EGF is an epidermal growth factor‐like region. Arrows indicate the location of possible glycosylation sites. There is also a dileucine motif in the 3¢ end of the enzyme that is important in intracellular trafficking of the enzyme to the melanosome.


Badolato R, Prandini A, Caracciolo S, et al. (2012) Exome sequencing reveals a pallidin mutation in a Hermansky‐Pudlak‐like primary immunodeficiency syndrome. Blood 119 (13): 3185–3187.

Brilliant MH (2015) Albinism in Africa: a medical and social emergency. International Health 7 (4): 223–225.

Chi A, Valencia JC, Hu ZZ, et al. (2006) Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. Journal of Proteome Research 5 (11): 3135–3144.

Cooksey CJ, Garratt PJ, Land EJ, et al. (1997) Evidence of the indirect formation of the catecholic intermediate substrate responsible for the autoactivation kinetics of tyrosinase. Journal of Biological Chemistry 272 (42): 26226–26235.

Cruz‐Inigo AE, Ladizinski B and Sethi A (2011) Albinism in Africa: stigma, slaughter and awareness campaigns. Dermatologic Clinics 29 (1): 79–87.

Dessinioti C, Stratigos AJ, Rigopoulos D and Katsambas AD (2009) A review of genetic disorders of hypopigmentation: lessons learned from the biology of melanocytes. Experimental Dermatology 18 (9): 741–749.

Giebel LB, Tripathi RK, Strunk KM, et al. (1991) Tyrosinase gene mutations associated with type IB (“yellow”) oculocutaneous albinism. American Journal of Human Genetics 48 (6): 1159–1167.

Gronskov K, Dooley CM, Ostergaard E, et al. (2013) Mutations in c10orf11, a melanocyte‐differentiation gene, cause autosomal‐recessive albinism. American Journal of Human Genetics 92 (3): 415–421.

Haefemeyer JW and Knuth JL (1991) Albinism. Journal of Ophthalmic Nursing & Technology 10 (2): 55–62.

Halaban R, Svedine S, Cheng E, et al. (2000) Endoplasmic reticulum retention is a common defect associated with tyrosinase‐negative albinism. Proceedings of the National Academy of Sciences of the United States of America 97 (11): 5889–5894.

Han J, Kraft P, Nan H, et al. (2008) A genome‐wide association study identifies novel alleles associated with hair color and skin pigmentation. PLoS Genetics 4 (5): e1000074.

Hoyle DJ, Rodriguez‐Fernandez IA and Dell'angelica EC (2011) Functional interactions between OCA2 and the protein complexes BLOC‐1, BLOC‐2, and AP‐3 inferred from epistatic analyses of mouse coat pigmentation. Pigment Cell & Melanoma Research 24 (2): 275–281.

Huizing M, Anikster Y and Gahl WA (2001) Hermansky‐Pudlak syndrome and Chediak‐Higashi syndrome: disorders of vesicle formation and trafficking. Journal of Thrombosis and Haemostasis 86 (1): 233–245.

Inagaki K, Suzuki T, Shimizu H, et al. (2004) Oculocutaneous albinism type 4 is one of the most common types of albinism in Japan. American Journal of Human Genetics 74 (3): 466–471.

Ito S and Wakamatsu K (2008) Chemistry of mixed melanogenesis–pivotal roles of dopaquinone. Photochemistry and Photobiology 84 (3): 582–592.

Kausar T, Bhatti MA, Ali M, Shaikh RS and Ahmed ZM (2013) OCA5, a novel locus for non‐syndromic oculocutaneous albinism, maps to chromosome 4q24. Clinical Genetics 84 (1): 91–93.

King RA, Hearing VJ, Creel DJ and Oetting WS (2014) Albinism. In: Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson KM and Mitchell G (eds) The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: The McGraw‐Hill Companies, Inc.

King RA, Mentink MM and Oetting WS (1991) Non‐random distribution of missense mutations within the human tyrosinase gene in type I (tyrosinase‐related) oculocutaneous albinism. Molecular Biology & Medicine 8 (1): 19–29.

King RA, Pietsch J, Fryer JP, et al. (2003) Tyrosinase gene mutations in oculocutaneous albinism 1 (OCA1): definition of the phenotype. Human Genetics 113 (6): 502–513.

Kinnear PE, Jay B and Witkop CJ Jr (1985) Albinism. Survey of Ophthalmology 30 (2): 75–101.

Lopez VM, Decatur CL, Stamer WD, Lynch RM and McKay BS (2008) L‐DOPA is an endogenous ligand for OA1. PLoS Biology 6 (9): e236.

Manga P, Kromberg J, Turner A, Jenkins T and Ramsay M (2001) In Southern Africa, brown oculocutaneous albinism (BOCA) maps to the OCA2 locus on chromosome 15q: P‐gene mutations identified. American Journal of Human Genetics 68 (3): 782–787.

McKay BS (2018) Pigmentation and vision: Is GPR143 in control? Journal of Neuroscience Research. DOI: 10.1002/jnr.24246.

Montoliu L, Gronskov K, Wei AH, et al. (2014) Increasing the complexity: new genes and new types of albinism. Pigment Cell & Melanoma Research 27 (1): 11–18.

Newton JM, Cohen‐Barak O, Hagiwara N, et al. (2001) Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4. American Journal of Human Genetics 69 (5): 981–988.

Nordlund JJ (2006) The Pigmentary System: Physiology and Pathophysiology, 2nd edn. Malden, MA: Blackwell Pub.

Oetting WS, Fryer JP, Shriram S and King RA (2003) Oculocutaneous albinism type 1: the last 100 years. Pigment Cell & Melanoma Research 16 (3): 307–311.

Oetting WS, Pietsch J, Brott MJ, et al. (2009) The R402Q tyrosinase variant does not cause autosomal recessive ocular albinism. American Journal of Medical Genetics 149A: 466–469.

Pearson K, Nettleship E and Usher CH (1913) A Monograph on Albinism in Man. London: Drapers' Company Research Memoirs, Biometric Series IX.

Rundshagen U, Zuhlke C, Opitz S, Schwinger E and Kasmann‐Kellner B (2004) Mutations in the MATP gene in five German patients affected by oculocutaneous albinism type 4. Human Mutation 23 (2): 106–110.

Sarangarajan R and Boissy RE (2001) Tyrp1 and oculocutaneous albinism type 3. Pigment Cell & Melanoma Research 14 (6): 437–444.

Scherer D and Kumar R (2010) Genetics of pigmentation in skin cancer – a review. Mutation Research 705 (2): 141–153. DOI: 10.1016/j.mrrev.2010.06.002.

Simeonov DR, Wang X, Wang C, et al. (2013) DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics. Human Mutation 34 (6): 827–835.

Sturm RA, Teasdale RD and Box NF (2001) Human pigmentation genes: identification, structure and consequences of polymorphic variation. Gene 277 (1–2): 49–62.

Sulem P, Gudbjartsson DF, Stacey SN, et al. (2007) Genetic determinants of hair, eye and skin pigmentation in Europeans. Nature Genetics 39 (12): 1443–1452. DOI: 10.1038/ng.2007.13.

Summers CG (1996) Vision in albinism. Transactions of the American Ophthalmological Society 94: 1095–1155.

Summers CG (2009) Albinism: classification, clinical characteristics, and recent findings. Optometry and Vision Science 86 (6): 659–662.

Tibber MS, Becker D and Jeffery G (2007) Levels of transient gap junctions between the retinal pigment epithelium and the neuroblastic retina are influenced by catecholamines and correlate with patterns of cell production. The Journal of Comparative Neurology 503 (1): 128–134.

Toro C, Nicoli ER, Malicdan MC, Adams DR and Introne WJ (1993) Chediak‐Higashi syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K and Amemiya A (eds) GeneReviews((R)). Seattle, WA: University of Washington.

Toyofuku K, Wada I, Spritz RA and Hearing VJ (2001) The molecular basis of oculocutaneous albinism type 1 (OCA1): sorting failure and degradation of mutant tyrosinases results in a lack of pigmentation. Biochemical Journal 355 (Pt 2): 259–269.

Tripathi RK, Strunk KM, Giebel LB, Weleber RG and Spritz RA (1992) Tyrosinase gene mutations in type I (tyrosinase‐deficient) oculocutaneous albinism define two clusters of missense substitutions. American Journal of Medical Genetics 43 (5): 865–871.

Valenzuela RK, Henderson MS, Walsh MH, et al. (2010) Predicting phenotype from genotype: normal pigmentation. Journal of Forensic Science 55 (2): 315–322.

Walsh S, Chaitanya L, Breslin K, et al. (2017) Global skin colour prediction from DNA. Human Genetics 136 (7): 847–863.

Wei AH, Zang DJ, Zhang Z, et al. (2013) Exome sequencing identifies SLC24A5 as a candidate gene for nonsyndromic oculocutaneous albinism. Journal of Investigative Dermatology 133 (7): 1834–1840.

Zhang KH, Li Z, Lei J, et al. (2011) Oculocutaneous albinism type 3 (OCA3): analysis of two novel mutations in TYRP1 gene in two Chinese patients. Cell Biochemistry and Biophysics 61 (3): 523–529.

Web Links

The Albinism Database, (accessed 9 September 2018).

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Oetting, William S, and Adams, David(Nov 2018) Albinism: Genetics. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0006081.pub3]