GeneBe

SLC24A5

protein-coding

solute carrier family 24 member 5, the group of Solute carrier family 24

Gene 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 associated with differences in skin pigmentation. [provided by RefSeq, Jul 2008]

MANE transcript

NM_205850.3

Inheritance

AR

ClinVar variants

P:41U:136B:77

Top phenotype

Albinism, oculocutaneous, type VI

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr15:48,120,990-48,142,672

External References & Databases

Ensembl (ENSG00000188467)NCBI Gene (283652)OMIM (609802)HGNC:20611GenCCUniProt (Q71RS6)AlphaFoldClinVar (SLC24A5)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~21.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

oculocutaneous albinism type 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0018264

Submitter: PanelApp Australia

oculocutaneous albinism type 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0018264

Submitter: Labcorp Genetics (formerly Invitae)

oculocutaneous albinism type 6SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018264

Submitter: Orphanet

oculocutaneous albinism type 6DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018264

Submitter: G2P

oculocutaneous albinism type 6DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018264

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Albinism, oculocutaneous, type VIAR

Manifestation: Dermatologic; Ophthalmologic

Intervention: General

Rationale: 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

Comments: Variants may also influence relative pigmentation in the general population

Refs: 23364476Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC24A5 variants in ClinVar

7 Conditions Cataloged
not providedTotal: 255
Inborn genetic diseasesTotal: 47
SLC24A5-related disorderTotal: 16
Oculocutaneous albinism type 6Total: 12
not specifiedTotal: 6
Skin/hair/eye pigmentation, variation in, 4Total: 2
Oculocutaneous albinismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_205850.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
65
clinvar
2
clinvar
 69
missense
1
clinvar
3
clinvar
129
clinvar
10
clinvar
 143
nonsense
12
clinvar
2
clinvar
1
clinvar
 15
start loss
0
frameshift
13
clinvar
2
clinvar
2
clinvar
 17
splice donor/acceptor (+/-2bp)
8
clinvar
2
clinvar
 10
Total2615136752254

Highest pathogenic variant AF is 0.00014694923

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_205850.3RefSeqNP_995322.19MANE Select
ENST00000341459.8EnsemblENSP00000341550.39MANE Select
ENST00000449382.2EnsemblENSP00000389966.28Standard
ENST00000449382.3EnsemblENSP00000389966.28Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
slc24a5Danio rerio

Structure: melanocyte

Quality: decreased pigmentation

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Sodium/Calcium exchangers
  • Transport of inorganic cations/anions and amino acids/oligopeptides
  • SLC-mediated transmembrane transport
  • Transport of small molecules

Biological Process

  • ion transport
  • potassium ion transport
  • cellular calcium ion homeostasis
  • melanocyte differentiation
  • ion transmembrane transport

Molecular Function

  • calcium channel activity
  • calcium, potassium:sodium antiporter activity
  • symporter activity

Cellular Component

  • trans-Golgi network
  • integral component of membrane
  • trans-Golgi network membrane
  • melanosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000341459
Coding exons
9
Length
21701
Individuals with no LoFs
125609
Homozygous LoFs
1
Heterozygous LoFs
133
Defined
125743
p
0.000533
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.3172562710.9460.00001323232
Missense (PolyPhen)5970.7140.83435855
Synonymous-0.05991011001.010.000005251009
Loss of Function0.9741721.90.7759.23e-7289

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000180.00018rare
Latino/Admixed American0.000260.00026rare
Ashkenazi Jewish00.0absent
East Asian0.000160.00016rare
Finnish0.000830.00083rare
European (Non-Finnish)0.000760.00075rare
South Asian0.000490.00046rare
Other0.000330.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Cation exchanger involved in pigmentation, possibly by participating in ion transport in melanosomes. Predominant sodium- Calcium exchanger in melanocytes. Probably transports 1 Ca(2+) and 1 K(+) to the melanosome in exchange for 4 cytoplasmic Na(+). {ECO:0000269|PubMed:16357253, ECO:0000269|PubMed:18166528}.;
Disease
DISEASE: Albinism, oculocutaneous, 6 (OCA6) [MIM:113750]: A disorder characterized by a reduction or complete loss of melanin in the skin, hair and eyes. Patients show reduced or lacking pigmentation often accompanied by eye symptoms such as photophobia, strabismus, moderate to severe visual impairment, and nystagmus. {ECO:0000269|PubMed:23364476}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.194

Intolerance Scores

LoFtool
0.909
RVIS EVS
-0.69
RVIS percentile EVS
15.2

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.135

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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