SLC45A2

Summary

SLC45A2 (solute carrier family 45 member 2, HGNC:16472) is a protein-coding gene on chromosome 5p13.2, encoding Membrane-associated transporter protein (Q9UMX9). Proton-associated glucose and sucrose transporter.

This gene encodes a transporter protein that mediates melanin synthesis. The protein is expressed in a high percentage of melanoma cell lines. Mutations in this gene are a cause of oculocutaneous albinism type 4, and polymorphisms in this gene are associated with variations in skin and hair color. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 51151 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oculocutaneous albinism type 4 (Definitive, GenCC)
• GWAS associations: 66
• Clinical variants (ClinVar): 677 total — 73 pathogenic, 29 likely-pathogenic
• Phenotypes (HPO): 21
• MANE Select transcript: NM_016180

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16472
Approved symbol	SLC45A2
Name	solute carrier family 45 member 2
Location	5p13.2
Locus type	gene with protein product
Status	Approved
Aliases	AIM-1, OCA4
Ensembl gene	ENSG00000164175
Ensembl biotype	protein_coding
OMIM	606202
Entrez	51151

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000296589, ENST00000382102, ENST00000505056, ENST00000509381, ENST00000510600

RefSeq mRNA: 3 — MANE Select: NM_016180 NM_001012509, NM_001297417, NM_016180

CCDS: CCDS3901, CCDS43308, CCDS75232

Canonical transcript exons

ENST00000296589 — 7 exons

Exon	Start	End
ENSE00001082121	33963691	33964016
ENSE00001082122	33947163	33947374
ENSE00001082124	33982236	33982412
ENSE00001364358	33951554	33951677
ENSE00001853800	33944623	33944872
ENSE00001953232	33984199	33984693
ENSE00003557504	33954361	33954504

Expression profiles

Bgee: expression breadth broad, 100 present calls, max score 84.52.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6281 / max 134.9989, expressed in 106 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61227	0.3448	66
61228	0.2833	94

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.52	gold quality
pigmented layer of retina	UBERON:0001782	76.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.73	gold quality
right lobe of liver	UBERON:0001114	63.45	gold quality
islet of Langerhans	UBERON:0000006	62.43	gold quality
liver	UBERON:0002107	52.77	gold quality
metanephros cortex	UBERON:0010533	52.19	gold quality
right atrium auricular region	UBERON:0006631	50.98	gold quality
skin of leg	UBERON:0001511	50.93	gold quality
cardiac atrium	UBERON:0002081	50.70	gold quality
hypothalamus	UBERON:0001898	50.44	gold quality
adult mammalian kidney	UBERON:0000082	50.42	gold quality
fundus of stomach	UBERON:0001160	49.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	49.68	gold quality
zone of skin	UBERON:0000014	48.84	gold quality
left testis	UBERON:0004533	48.84	gold quality
metanephros	UBERON:0000081	48.64	gold quality
testis	UBERON:0000473	48.28	gold quality
right testis	UBERON:0004534	48.22	gold quality
skin of abdomen	UBERON:0001416	48.14	gold quality
rectum	UBERON:0001052	47.88	gold quality
prefrontal cortex	UBERON:0000451	47.45	gold quality
gall bladder	UBERON:0002110	47.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	47.09	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	47.04	gold quality
kidney	UBERON:0002113	46.80	gold quality
cortex of kidney	UBERON:0001225	46.71	gold quality
ganglionic eminence	UBERON:0004023	46.57	gold quality
gastrocnemius	UBERON:0001388	46.48	gold quality
spinal cord	UBERON:0002240	46.39	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	623.01
E-ENAD-20	yes	451.31
E-ANND-3	no	1.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MITF

Literature-anchored findings (GeneRIF, showing 40)

• mutation underlies new form of oculocutaneous albinism, OCA4 (PMID:11574907)
• a single-nucleotide polymorphism that has clear association with major human populations in terms of skin color. (PMID:11916009)
• Ten novel mutations; one deletion, two frameshift mutations, and seven missense mutations were found in German patients with oculocutaneous albinism type 4. (PMID:14722913)
• The 374Leu allele may contribute to pH changes favoring eumelanin synthesis in melanosomes. The Phe374 allele may alter proton transport and trafficking of melanosomal proteins. (PMID:15714523)
• The p.L374F allele in SLC45A2 is a more specific ancestry informative marker than the p.A111T allele in SLC24A5, as it clearly distinguishes Sri Lankans from Europeans. (PMID:16847698)
• tyrosinase and membrane associated transporter protein polymorphisms may have roles in oculocutaneous albinism type 1 and type 4 in the German population (PMID:17516931)
• The purpose of this study was to investigate the molecular basis of Oculocutaneous albinism among Indians using SLC45A2 as the candidate gene. (PMID:17768386)
• Most patients with AROA (autosomal recessive ocular albinism) represent phenotypically mild variants of oculocutaneous albinism , well over half of which is OCA1. (PMID:18326704)
• the variant allele c.1122C>G was associated with protection from MM, was consistently linked with dark hair, dark skin, dark eye color, solar lentigins and childhood sunburns, and is a melanoma susceptibility gene in a light-skinned population. (PMID:18563784)
• strong correlations in MATP-L374F, OCA2, and melanocortin-1 receptor with skin, eye, and hair color variation (PMID:18650849)
• the SLC45A2 variant p.Phe374Leu was significantly and strongly protective for melanoma; MC1R and SLC45A2 variants had additive effects on melanoma risk, and after adjusting for pigmentation characteristics, the risk was persistent (PMID:18683857)
• Variations in the SLC45A2 gene is associated with hair colour variation. (PMID:18806926)
• These novel mutations included one missense substitution D160H and one splice site mutation IVS5+3delAAGT. This is the first Chinese case report of oculocutaneous albinism type 4. (PMID:18986462)
• TYR is the major OCA (oculocutaneous albinism) gene in Denmark, but several patients do not have mutations in the investigated genes. (PMID:19060277)
• Single nucleotide polymorphisms in SLC45A2 is associated with melanoma. (PMID:19384953)
• The 374F mutation in the SLC45A2 gene alleles may reflect the ultraviolet radiation level and may thus be associated with skin color variation in these regions. (PMID:19916045)
• This study found a diminished perception of sad and fearful information under SSRI which was significant in the long allele group. These findings emphasize the importance of genetic variance in emotion processing research. (PMID:20381161)
• ). Sequence variations in rs11636232 and rs7170852 in HERC2, rs1800407 in OCA2 and rs16891982 in MATP showed additional association with eye colours (PMID:20457063)
• TYR gene mutations represent a relevant cause of oculocutaneous albinism in Italy, whereas mutations in P present a lower frequency. Clinical analysis revealed that the severity of the ocular manifestations depends on the degree of retinal pigmentation. (PMID:20861488)
• detected three reported pathogenic mutations of the membrane associated transporter protein gene (MATP), including G349R, D160H and P419L, and identified a novel pathogenic mutation c.870delC (PMID:21287499)
• analysis of a novel SNP associated with melanoma predisposition in the SLC45A2 gene (PMID:21559390)
• analysis of SLC45A2 and G6PC3 mutations in a single patient with oculocutaneous albinism and neutropenia [case report] (PMID:21677667)
• Three mutational alleles, R278X and R52I of the TYR gene and C229Y of the SLC45A2 gene, are added to the mutational spectra of Korean patients with oculocutaneous albinism (OCA) (PMID:22042571)
• The SLC45A2 gene analysis identified 1 novel mutation, p.D93N. (PMID:22294196)
• In South European populations, MC1R red hair color and SCL45A2 p.Phe374Leu variants are strong melanoma risk predictors. (PMID:22464347)
• A novel large deletion mutation was detected and identified in oculocutaneous albinism type IV. (PMID:22490798)
• We examined the association between 12 variants of four pigmentation-related genes (TYR, OCA2, SLC45A2, MC1R) and variations in the melanin index of 456 Japanese females using a multiple regression analysis. (PMID:23165166)
• We report four Pakistani albinism mutations, including three SLC45A2 alleles and one 22-nucleotide deletion in TYRP1. (PMID:23190901)
• Results show that almost all the African populations located below 16 degrees of latitude are fixed for the 374l allele of SLC45A2 gene. (PMID:23660638)
• molecular defects in SLC45A2 gene represent the 3.4% of people with oculocutaneous albinism in this cohort of Italian patients, similar to other Caucasian populations (PMID:24096233)
• High-resolution array-CGH in patients with oculocutaneous albinism identifies new deletions of the TYR, OCA2, and SLC45A2 genes and a complex rearrangement of the OCA2 gene. (PMID:24118800)
• we propose that natural selection in South Europeans is favoring the allele SLC45A2 374F. (PMID:25093503)
• We identitified a single missense substitution in SLC45A2 in 13 families with oculocutaneous albinism. (PMID:25703744)
• The results indicated that the D93N mutation causes OCA4 as a result of loss of MATP transport activity, and that the F374 allele confers significantly lower transport activity than L374. (PMID:25760657)
• The reduction of tyrosinase activity associated with the knockdown of MATP. (PMID:26057890)
• Mutation in MATP gene expression is associated with Oculocutaneous albinism type IV. (PMID:27019209)
• Study confirmed a significant role for IRF4 rs12203592 and SLC45A2 rs16891982 in the risk of cutaneous squamous cell carcinoma development in organ transplant recipients. (PMID:27566401)
• Our analysis revealed 10 sun-exposure-dependent gene expression quantitative trait loci (se-eQTLs), including genes involved in skin pigmentation (SLC45A2) and epidermal differentiation (RASSF9). (PMID:27760139)
• Evaluating the influence of haplotypes of 12 SNPs within SLC45A2 in the determination of eye, hair and skin pigmentation in a highly admixed population sample and comparing their frequencies with the ones found in data retrieved from the 1000 Genomes Project. Results emphasize the role played by haplotypes at SLC45A2 in the determination of pigmentation and reinforce the relevance of SNP L374F in human pigmentation. (PMID:28457509)
• our study demonstrates the feasibility of using tandem MS as a means of discovering shared immunogenic tumor-associated epitopes and identifies SLC45A2 as a promising immunotherapeutic target for melanoma with high tumor selectivity and reduced potential for autoimmune toxicity (PMID:28630054)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc45a2	ENSDARG00000002593
mus_musculus	Slc45a2	ENSMUSG00000022243
rattus_norvegicus	Slc45a2	ENSRNOG00000018759
drosophila_melanogaster	Slc45-1	FBGN0035968
drosophila_melanogaster	lovit	FBGN0267429

Paralogs (3): SLC45A4 (ENSG00000022567), SLC45A3 (ENSG00000158715), SLC45A1 (ENSG00000162426)

Protein

Protein identifiers

Membrane-associated transporter protein — Q9UMX9 (reviewed: Q9UMX9)

Alternative names: Melanoma antigen AIM1, Solute carrier family 45 member 2

All UniProt accessions (4): A0A076YIB8, D6RBP8, D6RGY6, Q9UMX9

UniProt curated annotations — full annotation on UniProt →

Function. Proton-associated glucose and sucrose transporter. May be able to transport also fructose. Expressed at a late melanosome maturation stage where functions as proton/glucose exporter which increase lumenal pH by decreasing glycolysis. Regulates melanogenesis by maintaining melanosome neutralization that is initially initiated by transient OCA2 and required for a proper function of the tyrosinase TYR.

Subunit / interactions. Interacts with TYRP1.

Subcellular location. Melanosome membrane.

Tissue specificity. Expressed in mature melanocytes.

Disease relevance. Albinism, oculocutaneous, 4 (OCA4) [MIM:606574] A disorder of pigmentation characterized by reduced biosynthesis of melanin in the skin, hair and eyes. Patients show reduced or lacking pigmentation associated with classic albinism ocular abnormalities, including decreased visual acuity, macular hypoplasia, optic dysplasia, atypical choroidal vessels, and nystagmus. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. Genetic variants in SLC45A2 define the skin/hair/eye pigmentation variation locus 5 (SHEP5) [MIM:227240]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair.

Similarity. Belongs to the glycoside-pentoside-hexuronide (GPH) cation symporter transporter (TC 2.A.2) family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UMX9-1	1, AIM-1a	yes
Q9UMX9-2	2, AIM-1b
Q9UMX9-3	3, AIM-1c
Q9UMX9-4	4

RefSeq proteins (3): NP_001012527, NP_001284346, NP_057264* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011701	MFS	Family
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF07690

Catalyzed reactions (Rhea), 2 shown:

• D-glucose(out) + H(+)(out) = D-glucose(in) + H(+)(in) (RHEA:69556)
• sucrose(out) + H(+)(out) = sucrose(in) + H(+)(in) (RHEA:72187)

UniProt features (61 total): sequence variant 28, topological domain 13, transmembrane region 12, splice variant 6, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UMX9-F1	77.96	0.35

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 356

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5662702	Melanin biosynthesis
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 137 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_VACUOLE_ORGANIZATION, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_PIGMENTATION, ONKEN_UVEAL_MELANOMA_UP, GOBP_AROMATIC_AMINO_ACID_METABOLIC_PROCESS, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_PIGMENT_METABOLIC_PROCESS, JIANG_TIP30_TARGETS_DN, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_DEVELOPMENTAL_PIGMENTATION, GOBP_REGULATION_OF_PH

GO Biological Process (8): melanin biosynthetic process from tyrosine (GO:0006583), visual perception (GO:0007601), sucrose transport (GO:0015770), lysosomal lumen pH elevation (GO:0035752), developmental pigmentation (GO:0048066), hexose transmembrane transport (GO:0008645), melanin biosynthetic process (GO:0042438), transmembrane transport (GO:0055085)

GO Molecular Function (4): D-glucose:proton symporter activity (GO:0005356), sucrose:proton symporter activity (GO:0008506), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857)

GO Cellular Component (2): membrane (GO:0016020), melanosome membrane (GO:0033162)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
melanin biosynthetic process	1
sensory perception of light stimulus	1
disaccharide transport	1
intracellular pH elevation	1
pigmentation	1
monosaccharide transmembrane transport	1
melanin metabolic process	1
secondary metabolite biosynthetic process	1
pigment biosynthetic process	1
phenol-containing compound biosynthetic process	1
transport	1
cellular process	1
hexose:proton symporter activity	1
D-glucose transmembrane transporter activity	1
carbohydrate:proton symporter activity	1
sucrose:monoatomic cation symporter activity	1
secondary active transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
cellular anatomical structure	1
melanosome	1
chitosome	1
pigment granule membrane	1

Protein interactions and networks

STRING

1267 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC45A2	SLC24A5	Q71RS6	983
SLC45A2	OCA2	Q04671	976
SLC45A2	TYR	P14679	947
SLC45A2	TYRP1	P17643	933
SLC45A2	MC1R	Q01726	907
SLC45A2	SLC24A4	Q8NFF2	854
SLC45A2	EDAR	Q9UNE0	836
SLC45A2	TPCN2	Q8NHX9	799
SLC45A2	EDA2R	Q9HAV5	788
SLC45A2	ASIP	P42127	763
SLC45A2	GPR143	P51810	749
SLC45A2	IRF4	Q15306	712
SLC45A2	LRMDA	Q9H2I8	704
SLC45A2	MFSD12	Q6NUT3	689
SLC45A2	PMEL	P40967	659

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SLC45A2	GAPDHS	psi-mi:“MI:0915”(physical association)	0.400
SLC45A2	ACACB	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): GAPDHS (Affinity Capture-MS), SLC45A2 (Affinity Capture-MS), SQRDL (Affinity Capture-MS), UBB (Affinity Capture-MS), ATG9A (Affinity Capture-MS), CYHR1 (Affinity Capture-MS), FAM63A (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), MID1IP1 (Affinity Capture-MS), GTF2E1 (Affinity Capture-MS), AMFR (Affinity Capture-MS), TMEM63A (Affinity Capture-MS), SLC45A2 (Affinity Capture-MS), GAPDHS (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4ILB2, A0A8M9Q308, A1A4N1, A2CER7, A5D7V7, A8WGF7, B0S5Y3, B2RXV4, B5X4H8, O00400, O00476, O01735, O23596, P30638, P36836, P46029, P60815, Q11073, Q16348, Q28722, Q28FF3, Q503P5, Q5F4B8, Q5RBM3, Q5XGK0, Q63424, Q6AYY8, Q6DDL7, Q6DIT7, Q6GMG6, Q6PB15, Q7Z3Q1, Q84XI3, Q86WB7, Q91X85, Q944P0, Q99808, Q99J27, Q9BZD2, Q9C8X2

Diamond homologs: P58355, Q0P5V9, Q4LE88, Q5BKX6, Q8BIV7, Q8K4S3, Q9UMX9, Q9Y2W3, A2ZN77, B8AF63, Q03411, Q0ILJ3, Q10R54, Q39231, Q39232, Q6YK44, Q8K0H7, Q944W2, Q948L0, Q95KI5, Q96JT2, Q9FE59, Q9LKH3, Q67YF8, Q9C8X2, Q9FG00

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	73
Likely pathogenic	29
Uncertain significance	234
Likely benign	251
Benign	25

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1008770	NC_000005.10:g.33985072_33985075del	Pathogenic
1184503	NM_016180.5(SLC45A2):c.533_534dup (p.Gly179fs)	Pathogenic
1334440	NM_016180.5(SLC45A2):c.563G>T (p.Gly188Val)	Pathogenic
1365427	NM_016180.5(SLC45A2):c.1538C>A (p.Ala513Glu)	Pathogenic
1397714	NM_016180.5(SLC45A2):c.1305dup (p.Ser436fs)	Pathogenic
1451393	NM_016180.5(SLC45A2):c.1280T>C (p.Leu427Pro)	Pathogenic
1451401	NM_016180.5(SLC45A2):c.277G>A (p.Asp93Asn)	Pathogenic
1454427	NM_016180.5(SLC45A2):c.626dup (p.Leu210fs)	Pathogenic
1458973	NM_016180.5(SLC45A2):c.614_617dup (p.Glu206fs)	Pathogenic
1496395	NM_016180.5(SLC45A2):c.130G>C (p.Gly44Arg)	Pathogenic
1520860	NC_000005.9:g.(?33961548)(33964014_?)del	Pathogenic
1895798	NM_016180.5(SLC45A2):c.3G>A (p.Met1Ile)	Pathogenic
1917650	NM_016180.5(SLC45A2):c.692del (p.Thr231fs)	Pathogenic
196474	NM_016180.5(SLC45A2):c.856C>T (p.Gln286Ter)	Pathogenic
1996835	NM_016180.5(SLC45A2):c.349del (p.Met117fs)	Pathogenic
2032637	NM_016180.5(SLC45A2):c.785C>G (p.Ser262Ter)	Pathogenic
2040027	NM_016180.5(SLC45A2):c.1201_1205del (p.Tyr401fs)	Pathogenic
209971	NM_016180.5(SLC45A2):c.1273del (p.Leu425fs)	Pathogenic
2127272	NM_016180.5(SLC45A2):c.1450C>T (p.Gln484Ter)	Pathogenic
2186144	NM_016180.5(SLC45A2):c.1329del (p.Phe443fs)	Pathogenic
2203615	NM_016180.5(SLC45A2):c.1532C>A (p.Ala511Glu)	Pathogenic
2203618	NM_016180.5(SLC45A2):c.1045G>A (p.Gly349Arg)	Pathogenic
2203624	NM_016180.5(SLC45A2):c.152_153del (p.Val51fs)	Pathogenic
2426277	NC_000005.9:g.(?33951639)(33951802_?)del	Pathogenic
2703404	NM_016180.5(SLC45A2):c.823A>T (p.Lys275Ter)	Pathogenic
2706457	NM_016180.5(SLC45A2):c.1347C>G (p.Tyr449Ter)	Pathogenic
2734705	NM_016180.5(SLC45A2):c.1156+1G>A	Pathogenic
2734706	NM_016180.5(SLC45A2):c.844G>T (p.Glu282Ter)	Pathogenic
2742936	NM_016180.5(SLC45A2):c.160_164del (p.Ala54fs)	Pathogenic
2743725	NM_016180.5(SLC45A2):c.1428C>A (p.Cys476Ter)	Pathogenic

SpliceAI

1148 predictions. Top by Δscore:

Variant	Effect	Δscore
5:33947164:T:TA	donor_gain	1.0000
5:33947173:T:TA	donor_gain	1.0000
5:33951552:A:AC	donor_gain	1.0000
5:33951553:C:CC	donor_gain	1.0000
5:33951553:CAAGA:C	donor_gain	1.0000
5:33951674:CAAT:C	acceptor_gain	1.0000
5:33951675:AATC:A	acceptor_loss	1.0000
5:33951676:ATCT:A	acceptor_loss	1.0000
5:33951678:C:CA	acceptor_loss	1.0000
5:33951678:C:CC	acceptor_gain	1.0000
5:33951679:T:A	acceptor_loss	1.0000
5:33954355:CATTA:C	donor_loss	1.0000
5:33954356:ATTAC:A	donor_loss	1.0000
5:33954357:TTA:T	donor_loss	1.0000
5:33954358:TA:T	donor_loss	1.0000
5:33954359:A:C	donor_loss	1.0000
5:33954360:C:CG	donor_loss	1.0000
5:33964497:T:TA	donor_gain	1.0000
5:33982408:CAAAG:C	acceptor_gain	1.0000
5:33984195:TTA:T	donor_loss	1.0000
5:33984196:TA:T	donor_loss	1.0000
5:33984197:A:AC	donor_gain	1.0000
5:33984198:C:CC	donor_gain	1.0000
5:33984198:C:CT	donor_loss	1.0000
5:33984198:CCTG:C	donor_gain	1.0000
5:33951546:AGACT:A	donor_loss	0.9900
5:33951547:GACT:G	donor_loss	0.9900
5:33951548:ACTT:A	donor_loss	0.9900
5:33951549:CT:C	donor_loss	0.9900
5:33951550:TTA:T	donor_loss	0.9900

AlphaMissense

3453 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:33984353:G:C	S77R	0.998
5:33984353:G:T	S77R	0.998
5:33984355:T:G	S77R	0.998
5:33954411:A:G	W328R	0.996
5:33954411:A:T	W328R	0.996
5:33984308:G:C	S92R	0.995
5:33984308:G:T	S92R	0.995
5:33984310:T:G	S92R	0.995
5:33954424:G:C	S323R	0.994
5:33954424:G:T	S323R	0.994
5:33954426:T:G	S323R	0.994
5:33963998:C:T	G194D	0.994
5:33984467:G:C	S39R	0.994
5:33984467:G:T	S39R	0.994
5:33984469:T:G	S39R	0.994
5:33947197:A:G	L445P	0.993
5:33947223:G:C	S436R	0.993
5:33947223:G:T	S436R	0.993
5:33947225:T:G	S436R	0.993
5:33963999:C:G	G194R	0.993
5:33982340:T:G	D153A	0.993
5:33984364:A:G	W74R	0.993
5:33984364:A:T	W74R	0.993
5:33947236:C:T	G432D	0.990
5:33954414:C:G	G327R	0.990
5:33954414:C:T	G327R	0.990
5:33982339:A:C	D153E	0.990
5:33982339:A:T	D153E	0.990
5:33982340:T:A	D153V	0.990
5:33984442:A:G	C48R	0.990

dbSNP variants (sampled 300 via entrez): RS1000018468 (5:33959832 G>A), RS1000049440 (5:33974402 C>A,T), RS1000092818 (5:33969414 T>C), RS1000229581 (5:33950660 T>C), RS1000390308 (5:33980116 G>A), RS1000419316 (5:33986346 T>G), RS1000439377 (5:33944571 C>A), RS1000477836 (5:33968456 A>G), RS1000528789 (5:33971132 A>T), RS1000561213 (5:33964715 T>A,C), RS1000565249 (5:33949029 A>G), RS1000575124 (5:33949509 G>A), RS1000754352 (5:33985109 A>G,T), RS1000791281 (5:33983867 C>T), RS1000824089 (5:33977512 G>A,T)

Disease associations

OMIM: gene MIM:606202 | disease phenotypes: MIM:606574

GenCC curated gene-disease

Disease	Classification	Inheritance
oculocutaneous albinism type 4	Definitive	Autosomal recessive

Mondo (3): oculocutaneous albinism type 4 (MONDO:0011683), cutaneous melanoma (MONDO:0005012), thrombocytopenia (MONDO:0002049)

Orphanet (1): Oculocutaneous albinism type 4 (Orphanet:79435)

HPO phenotypes

21 total (22 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000478	Abnormality of the eye
HP:0000505	Visual impairment
HP:0000613	Photophobia
HP:0000635	Blue irides
HP:0000639	Nystagmus
HP:0001010	Hypopigmentation of the skin
HP:0001022	Albinism
HP:0001072	Thickened skin
HP:0001104	Macular hypoplasia
HP:0001107	Ocular albinism
HP:0003764	Nevus
HP:0005599	Hypopigmentation of hair
HP:0007663	Reduced visual acuity
HP:0007703	Abnormal retinal pigmentation
HP:0007730	Iris hypopigmentation
HP:0007750	Hypoplasia of the fovea
HP:0007894	Fundus hypopigmentation
HP:0008069	Neoplasm of the skin
HP:0011364	White hair
HP:0025551	Optic nerve misrouting
HP:0012056	Cutaneous melanoma

GWAS associations

66 associations (top):

Study	Trait	p-value
GCST000114_2	Skin pigmentation	3.000000e-11
GCST000190_6	Black vs. blond hair color	1.000000e-17
GCST000191_5	Black vs. red hair color	9.000000e-14
GCST000371_6	Tanning	3.000000e-10
GCST000707_7	Hair color	4.000000e-20
GCST000710_1	Eye color	1.000000e-12
GCST001267_7	Melanoma	2.000000e-07
GCST002906_4	Skin colour saturation	1.000000e-09
GCST002907_1	Perceived skin darkness	3.000000e-08
GCST002908_4	Skin sensitivity to sun	7.000000e-06
GCST003019_1	Black vs. non-black hair color	1.000000e-06
GCST003327_1	Squamous cell carcinoma	3.000000e-28
GCST003479_5	Hair color	2.000000e-59
GCST003655_3	Cutaneous squamous cell carcinoma	1.000000e-13
GCST003726_5	Basal cell carcinoma	5.000000e-27
GCST003996_3	Monobrow	7.000000e-48
GCST004142_17	Melanoma	3.000000e-19
GCST004142_6	Melanoma	1.000000e-23
GCST004219_2	Skin pigmentation	1.000000e-09
GCST004574_7	Skin aging (microtopography measurement)	4.000000e-09
GCST005790_97	Rosacea symptom severity	2.000000e-10
GCST005897_33	Low tan response	2.000000e-176
GCST006075_5	Hair color	1.000000e-100
GCST006988_107	Blond vs. brown/black hair color	7.000000e-26
GCST006988_189	Blond vs. brown/black hair color	4.000000e-11
GCST006988_190	Blond vs. brown/black hair color	3.000000e-22
GCST006988_2	Blond vs. brown/black hair color	3.000000e-181
GCST006989_1	Brown vs. black hair color	2.000000e-308
GCST007451_2	Skin, hair and eye pigmentation (multivariate analysis)	9.000000e-127
GCST007452_1	Skin pigmentation	1.000000e-117

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0003924	hair color
EFO:0004279	suntan
EFO:0003949	eye color
EFO:1001927	cutaneous squamous cell carcinoma
EFO:0007906	synophrys measurement
EFO:0009180	rosacea severity measurement
EFO:0009764	eye colour measurement
EFO:0003963	freckles
EFO:0010176	keratinocyte carcinoma
EFO:0004632	nevus count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C564696	Oculocutaneous Albinism, Type IV (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC45 family of putative sugar transporters

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
propionaldehyde	decreases expression	1
potassium perchlorate	decreases expression	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
clothianidin	decreases expression	1
3-iodothyronamine	affects uptake	1
theaflavin-3,3’-digallate	affects expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	decreases expression	1
Calcitriol	increases expression, affects cotreatment	1
Colforsin	increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Xylitol	decreases expression	1
Cyclosporine	increases methylation	1
Aflatoxin B1	increases methylation	1
Sodium Selenite	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT00019682	PHASE3	COMPLETED	Aldesleukin With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Melanoma
NCT00110019	PHASE3	COMPLETED	Carboplatin and Paclitaxel With or Without Sorafenib Tosylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
NCT01274338	PHASE3	ACTIVE_NOT_RECRUITING	Ipilimumab or High-Dose Interferon Alfa-2b in Treating Patients With High-Risk Stage III-IV Melanoma That Has Been Removed by Surgery
NCT01989572	PHASE3	COMPLETED	Sargramostim, Vaccine Therapy, or Sargramostim and Vaccine Therapy in Preventing Disease Recurrence in Patients With Melanoma That Has Been Removed By Surgery
NCT02288897	PHASE3	TERMINATED	PV-10 vs Chemotherapy or Oncolytic Viral Therapy for Treatment of Locally Advanced Cutaneous Melanoma
NCT02506153	PHASE3	ACTIVE_NOT_RECRUITING	Physician/Patient Choice of Either High-Dose Recombinant Interferon Alfa-2B or Ipilimumab, Versus Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery
NCT06320353	PHASE3	UNKNOWN	Study сomparing the Efficacy and Safety of RPH-075 and Keytruda® in Patients With Unresectable or Metastatic Skin Melanoma
NCT07068074	PHASE3	NOT_YET_RECRUITING	A Randomized Phase III Study of Management of Treatment Naive Primary Melanoma in Elderly Patients
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia