SLC24A5 (solute carrier family 24 member 5)

Gene

• Entrez ID: 283652
• Gene name: Solute carrier family 24 member 5
• Gene symbol: SLC24A5
• Synonyms (NCBI Gene): JSX, NCKX5, OCA6, SHEP4
• Chromosome: 15
• Chromosome location: 15q21.1
• Summary: This gene is a member of the potassium-dependent sodium/calcium exchanger family and encodes an intracellular membrane protein with 2 large hydrophilic loops and 2 sets of multiple transmembrane-spanning segments. Sequence variation in this gene has been

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005262	Function	Calcium channel activity	IBA
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005794	Component	Golgi apparatus	IEA
GO:0005802	Component	Trans-Golgi network	IBA
GO:0005802	Component	Trans-Golgi network	IDA	18166528
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006811	Process	Monoatomic ion transport	TAS
GO:0006813	Process	Potassium ion transport	IEA
GO:0006814	Process	Sodium ion transport	IEA
GO:0006816	Process	Calcium ion transport	IEA
GO:0006874	Process	Intracellular calcium ion homeostasis	IBA
GO:0008273	Function	Calcium, potassium:sodium antiporter activity	IBA
GO:0008273	Function	Calcium, potassium:sodium antiporter activity	IDA	18166528, 27093457
GO:0008273	Function	Calcium, potassium:sodium antiporter activity	IEA
GO:0008273	Function	Calcium, potassium:sodium antiporter activity	TAS
GO:0015085	Function	Calcium ion transmembrane transporter activity	IEA
GO:0015293	Function	Symporter activity	IEA
GO:0015297	Function	Antiporter activity	IEA
GO:0016020	Component	Membrane	IEA
GO:0032588	Component	Trans-Golgi network membrane	TAS
GO:0034220	Process	Monoatomic ion transmembrane transport	IDA	18166528
GO:0035725	Process	Sodium ion transmembrane transport	IEA
GO:0042438	Process	Melanin biosynthetic process	IEA
GO:0042470	Component	Melanosome	IEA
GO:0048022	Process	Negative regulation of melanin biosynthetic process	IEA
GO:0055085	Process	Transmembrane transport	IEA
GO:0070509	Process	Calcium ion import	IDA	27093457
GO:0070509	Process	Calcium ion import	IEA
GO:0070588	Process	Calcium ion transmembrane transport	IBA
GO:0071805	Process	Potassium ion transmembrane transport	IEA

Other IDs

• MIM: 609802
• HGNC: 20611
• e!Ensembl: ENSG00000188467

Protein

• UniProt ID: Q71RS6
• Protein name: Sodium/potassium/calcium exchanger 5 (Na(+)/K(+)/Ca(2+)-exchange protein 5) (Solute carrier family 24 member 5)
• Protein function: Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) to the melanosome in exchange for 4 cytoplasmic Na(+) (PubMed:18166528). Involved in pigmentation, possibly by participating in ion transport in melanosomes (PubMed:1635725
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01699	Na_Ca_ex	71 → 216	Sodium/calcium exchanger protein	Family
  PF01699	Na_Ca_ex	333 → 484	Sodium/calcium exchanger protein	Family

• Sequence:

  MQTKGGQTWARRALLLGILWATAHLPLSGTSLPQRLPRATGNSTQCVISPSSEFPEGFFT
  RQERRDGGIIIYFLIIVYMFMAISIVCDEYFLPSLEIISESLGLSQDVAGTTFMAAGSSA
  PELVTAFLGVFITKGDIGISTILGSAIYNLLGICAACGLLSNTVSTLSCWPLFRDCAAYT
  ISAAAVLGIIYDNQVYWYEGALLLLIYGLYVLVLCFDIKINQYIIKKCSPCCACLAKAME
  RSEQQPLMGWEDEGQPFIRRQSRTDSGIFYEDSGYSQLSISLHGLSQVSEDPPSVFNMPE
  ADLKRIFWVLSLPIITLLFLTTPDCRKKFWKNYFVITFFMSAIWISAFTYILVWMVTITG
  ETLEIPDTVMGLTLLAAGTSIPDTIASVLVARKGKGDMAMSNIVGSNVFDMLCLGIPWFI
  KTAFINGSAPAEVNSRGLTYITISLNISIIFLFLAVHFNGWKLDRKLGIVCLLSYLGLAT
  LSVLYELGIIGNNKIRGCGG

• Sequence length: 500

Pathways

Reactome:

Sodium/Calcium exchangers
Defective SLC24A5 causes oculocutaneous albinism 6 (OCA6)

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Oculocutaneous albinism	Likely pathogenic	rs1450652793	RCV000826128	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Oculocutaneous albinism type 6	Pathogenic; Likely pathogenic	rs2504597755, rs2038684395, rs1555452574, rs772398324, rs1555452572, rs886037643, rs886037644	RCV003129571 RCV003889360 RCV000500925 RCV000508792 RCV000508896 RCV000054447 RCV000054448	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Skin/hair/eye pigmentation, variation in, 4	Pathogenic	rs977118193	RCV000851387	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SLC24A5-related disorder	Pathogenic	rs772398324	RCV004758029	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Uveal melanoma	Likely pathogenic	rs1450652793	RCV005902147	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
BENIGN NEOPLASM OF EYE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CUTANEOUS MELANOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLAUCOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OPEN-ANGLE GLAUCOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PULMONARY ARTERIAL HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN NEOPLASM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN-HAIR-EYE PIGMENTATION, VARIATION IN, 4	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Albinism	Albinism	Pubtator	32966289, 35488210	Associate	★☆☆☆☆ Found in Text Mining only
Albinism Ocular	Ocular albinism	Pubtator	30679655	Associate	★☆☆☆☆ Found in Text Mining only
Albinism Oculocutaneous	Oculocutaneous albinism	Pubtator	22734612, 27129268, 30679655, 31077556	Associate	★☆☆☆☆ Found in Text Mining only
Albinism, Ocular	Ocular albinism	BEFREE	27734839		★☆☆☆☆ Found in Text Mining only
Albinism, Oculocutaneous	Oculocutaneous albinism	BEFREE	23364476, 26165494, 27129268, 27734839, 28525403, 31201282, 31486119		★☆☆☆☆ Found in Text Mining only
Albinism, Oculocutaneous	Oculocutaneous albinism	GENOMICS_ENGLAND_DG	23364476		★☆☆☆☆ Found in Text Mining only
ALBINISM, OCULOCUTANEOUS, TYPE VI	Oculocutaneous albinism	GENOMICS_ENGLAND_DG	23364476, 23985994, 26686029		★☆☆☆☆ Found in Text Mining only
ALBINISM, OCULOCUTANEOUS, TYPE VI	Oculocutaneous albinism	BEFREE	27129268, 30204049, 31486119		★☆☆☆☆ Found in Text Mining only
ALBINISM, OCULOCUTANEOUS, TYPE VI	Oculocutaneous albinism	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	33318654	Associate	★☆☆☆☆ Found in Text Mining only
Chronic kidney disease stage 5	Kidney Disease	BEFREE	24871321		★☆☆☆☆ Found in Text Mining only
Color Vision Defects	Color vision deficiency	Pubtator	23555287	Associate	★☆☆☆☆ Found in Text Mining only
Disorder of eye	Disorder Of Eye	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Hypopigmentation disorder	Hypopigmentation Disorder	BEFREE	23010199		★☆☆☆☆ Found in Text Mining only
Kidney Failure, Chronic	Kidney Failure	BEFREE	24871321		★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	Pubtator	28683437	Associate	★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	28692664		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	32966289, 33167923	Associate	★☆☆☆☆ Found in Text Mining only
Melanoma Amelanotic	Melanoma	Pubtator	32966289	Associate	★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ocular albinism, type I	Ocular albinism	BEFREE	27734839, 30679655		★☆☆☆☆ Found in Text Mining only
Oculocutaneous albinism type 1	Oculocutaneous albinism	Pubtator	31077556	Associate	★☆☆☆☆ Found in Text Mining only
Oculocutaneous albinism type 6	Oculocutaneous albinism	ORPHANET_DG	23364476		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Oculocutaneous albinism type 6	Oculocutaneous albinism	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Oculocutaneous albinism type 6	Oculocutaneous albinism	BEFREE	30204049		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Oculocutaneous albinism type 6	Oculocutaneous albinism	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	26584285	Associate	★☆☆☆☆ Found in Text Mining only
Rufous oculocutaneous albinism	Rufous oculocutaneous albinism	Pubtator	31077556	Associate	★☆☆☆☆ Found in Text Mining only