OCA2

OCA2 melanosomal transmembrane protein

Basic information

Region (hg38): 15:27754875-28099315

Previous symbols: [ "D15S12", "P", "EYCL3", "EYCL2" ]

Links

ENSG00000104044 ∙ NCBI:4948 ∙ OMIM:611409 ∙ HGNC:8101 ∙ Uniprot:Q04671 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• oculocutaneous albinism type 2 (Definitive), mode of inheritance: AR
• oculocutaneous albinism type 2 (Supportive), mode of inheritance: AR
• oculocutaneous albinism type 2 (Definitive), mode of inheritance: AR
• oculocutaneous albinism type 2 (Strong), mode of inheritance: AR
• oculocutaneous albinism type 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Albinism, oculocutaneous, type II; Albinism, brown oculocutaneous; Skin/hair/eye pigmentation 1	AD/AR	General	In Albinism, oculocutaneous, type II; Albinism, brown oculocutaneous, Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Skin/hair/eye pigmentation 1 is a susceptibility factor locus for a multifactorial disease (melanoma)	Dermatologic; Ophthalmologic	14904868; 687204; 7920637; 8302318; 7874125; 7762554; 7887411; 8723691; 10649493; 11179026; 12163334; 14704187; 15889046; 16341609; 17236130; 17952075; 18449927; 18680187; 20861488; 21471978; 21085994; 23103111

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OCA2 gene.

• not provided (92 variants)
• Tyrosinase-positive oculocutaneous albinism (19 variants)
• SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES (15 variants)
• OCA2-related disorder (6 variants)
• Oculocutaneous albinism (3 variants)
• Hypophosphatasia (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OCA2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	4	255	13	273
missense	14	45	251	21	7	338
nonsense	24	7	1			32
start loss						0
frameshift	45	29	2			76
inframe indel		2	5			7
splice donor/acceptor (+/-2bp)	24	30				54
splice region		4	31	48	2	85
non coding	1	4	13	176	65	259
Total	108	118	276	452	85

Highest pathogenic variant AF is 0.000131

Variants in OCA2

This is a list of pathogenic ClinVar variants found in the OCA2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-27754978-G-T		Tyrosinase-positive oculocutaneous albinism	Uncertain significance (Jan 12, 2018)
15-27755017-C-G		Tyrosinase-positive oculocutaneous albinism	Uncertain significance (Apr 27, 2017)
15-27755021-G-C		Tyrosinase-positive oculocutaneous albinism	Uncertain significance (Jan 12, 2018)
15-27755088-A-G		Tyrosinase-positive oculocutaneous albinism	Uncertain significance (Jan 12, 2018)
15-27755117-C-T		Tyrosinase-positive oculocutaneous albinism	Likely benign (Apr 27, 2017)
15-27755222-G-A		Tyrosinase-positive oculocutaneous albinism	Uncertain significance (Jan 13, 2018)
15-27755334-T-C		Tyrosinase-positive oculocutaneous albinism • Tyrosinase-positive oculocutaneous albinism;SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES	Uncertain significance (Oct 15, 2021)
15-27755338-T-C		Tyrosinase-positive oculocutaneous albinism	Benign (Jan 13, 2018)
15-27755367-C-T		Tyrosinase-positive oculocutaneous albinism	Uncertain significance (Jan 12, 2018)
15-27755387-A-G		Tyrosinase-positive oculocutaneous albinism	Uncertain significance (Nov 07, 2021)
15-27755391-A-G			Likely benign (Nov 10, 2023)
15-27755398-CCCA-C			Uncertain significance (Feb 23, 2022)
15-27755399-C-T			Uncertain significance (Mar 12, 2022)
15-27755401-AC-A			Uncertain significance (Feb 22, 2022)
15-27755403-C-A			Likely benign (Jan 17, 2024)
15-27755403-C-T			Likely benign (May 11, 2023)
15-27755404-A-T			Uncertain significance (Jun 20, 2022)
15-27755405-C-T			Benign (Jan 31, 2024)
15-27755408-C-T			Benign (Jan 27, 2024)
15-27755411-G-A			Uncertain significance (Aug 10, 2022)
15-27755414-C-G		Oculocutaneous albinism	Pathogenic/Likely pathogenic (May 01, 2024)
15-27755424-A-C			Pathogenic (Sep 21, 2023)
15-27755426-AAC-A			Pathogenic (Oct 29, 2023)
15-27755430-C-T			Uncertain significance (Oct 13, 2022)
15-27755432-T-A			Conflicting classifications of pathogenicity (Nov 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OCA2	protein_coding	protein_coding	ENST00000354638	23	344484

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.91e-13	0.968	125641	0	107	125748	0.000426

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.833	535	483	1.11	0.0000319	5393
Missense in Polyphen		204	172.73	1.181		2047
Synonymous	-1.42	232	206	1.13	0.0000154	1750
Loss of Function	2.32	27	43.5	0.621	0.00000210	501

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00492	0.00368
Ashkenazi Jewish	0.00	0.00
East Asian	0.000437	0.000435
Finnish	0.00	0.00
European (Non-Finnish)	0.000266	0.000264
Middle Eastern	0.000437	0.000435
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Could be involved in the transport of tyrosine, the precursor to melanin synthesis, within the melanocyte. Regulates the pH of melanosome and the melanosome maturation. One of the components of the mammalian pigmentary system. Seems to regulate the post-translational processing of tyrosinase, which catalyzes the limiting reaction in melanin synthesis. May serve as a key control point at which ethnic skin color variation is determined. Major determinant of brown and/or blue eye color. {ECO:0000269|PubMed:11310796, ECO:0000269|PubMed:15262401, ECO:0000269|PubMed:18252222, ECO:0000269|PubMed:22234890, ECO:0000269|PubMed:7601462}.
• Disease: DISEASE: Albinism, oculocutaneous, 2 (OCA2) [MIM:203200]: An autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in skin, hair, and eyes. Although affected infants may appear at birth to have complete absence of melanin pigment, most patients acquire small amounts of pigment with age. Visual anomalies include decreased acuity and nystagmus. The phenotype is highly variable. The hair of affected individuals may turn darker with age, and pigmented nevi or freckles may be seen. African and African American individuals may have yellow hair and blue-gray or hazel irides. One phenotypic variant, 'brown OCA,' has been described in African and African American populations and is characterized by light brown hair and skin color and gray to tan irides. {ECO:0000269|PubMed:10649493, ECO:0000269|PubMed:10671067, ECO:0000269|PubMed:10987646, ECO:0000269|PubMed:12713581, ECO:0000269|PubMed:12727022, ECO:0000269|PubMed:12876664, ECO:0000269|PubMed:17385796, ECO:0000269|PubMed:23504663, ECO:0000269|PubMed:7762554, ECO:0000269|PubMed:7874125, ECO:0000269|PubMed:9259203}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Prader-Willi and Angelman Syndrome;Metabolism of amino acids and derivatives;Tyrosine metabolism;Biopterin metabolism;Metabolism;Melanin biosynthesis (Consensus)

Recessive Scores

• pRec: 0.366

Intolerance Scores

• loftool: 0.0878
• rvis_EVS: 0.13
• rvis_percentile_EVS: 62.75

Haploinsufficiency Scores

• pHI: 0.123
• hipred: N
• hipred_score: 0.300
• ghis: 0.449

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.208

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Oca2
• Phenotype: liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype; hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; vision/eye phenotype; digestive/alimentary phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; renal/urinary system phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype

Zebrafish Information Network

• Gene name: oca2
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: eye pigment biosynthetic process;spermatid development;cell population proliferation;tyrosine transport;melanocyte differentiation;melanin biosynthetic process;transmembrane transport
• Cellular component: cytoplasm;lysosomal membrane;endoplasmic reticulum membrane;endosome membrane;integral component of membrane;melanosome membrane
• Molecular function: transporter activity;L-tyrosine transmembrane transporter activity;protein binding