SLC24A4

solute carrier family 24 member 4, the group of Solute carrier family 24

Basic information

Region (hg38): 14:92322581-92501481

Links

ENSG00000140090 ∙ NCBI:123041 ∙ OMIM:609840 ∙ HGNC:10978 ∙ Uniprot:Q8NFF2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• amelogenesis imperfecta hypomaturation type 2A5 (Strong), mode of inheritance: AR
• amelogenesis imperfecta, type 3A (Supportive), mode of inheritance: AD
• amelogenesis imperfecta type 2 (Supportive), mode of inheritance: AR
• amelogenesis imperfecta hypomaturation type 2A5 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ameliogenesis imperfecta, hypomaturation type, IIA5	AR	General	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	Dental	23375655; 24621671

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC24A4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC24A4 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				17	6	23
missense			34	8	5	47
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1	2	4
non coding				2	27	29
Total	0	0	34	27	38

Variants in SLC24A4

This is a list of pathogenic ClinVar variants found in the SLC24A4 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-92323733-A-G			Benign (Nov 12, 2018)
14-92323835-C-G		Inborn genetic diseases	Uncertain significance (Sep 25, 2023)
14-92323843-G-T			Uncertain significance (Sep 01, 2019)
14-92323850-T-C		Inborn genetic diseases	Uncertain significance (Mar 17, 2023)
14-92323856-C-A		Inborn genetic diseases	Uncertain significance (Apr 16, 2024)
14-92323938-G-A		SLC24A4-related disorder	Benign (Dec 31, 2019)
14-92323938-G-T			Benign (Dec 31, 2019)
14-92324169-G-T			Benign (Jun 19, 2021)
14-92325547-C-T			Benign (Jun 19, 2021)
14-92325911-G-A			Benign (Jun 09, 2021)
14-92325945-G-A		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
14-92325969-A-G			Benign (Dec 31, 2019)
14-92326088-T-C			Benign (Jun 19, 2021)
14-92326260-C-T			Benign (Jun 19, 2021)
14-92326295-T-C			Benign (Jun 19, 2021)
14-92433913-G-A			Benign (Nov 20, 2018)
14-92433968-G-A		Inborn genetic diseases	Uncertain significance (Apr 09, 2024)
14-92433996-G-A			Likely benign (Jan 02, 2019)
14-92434161-A-T			Benign (Nov 12, 2018)
14-92439350-T-C		Inborn genetic diseases	Uncertain significance (Dec 15, 2023)
14-92439370-C-T			Likely benign (Jul 10, 2017)
14-92439473-A-G			Benign (Nov 12, 2018)
14-92442122-A-G		Inborn genetic diseases	Uncertain significance (Apr 07, 2022)
14-92442132-C-T		Amelogenesis imperfecta hypomaturation type 2A5	Pathogenic (Mar 12, 2014)
14-92442137-G-A		Inborn genetic diseases	Uncertain significance (Dec 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC24A4	protein_coding	protein_coding	ENST00000532405	17	173672

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.20e-11	0.962	125697	0	51	125748	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.805	340	384	0.884	0.0000229	4060
Missense in Polyphen		98	135.52	0.72315		1460
Synonymous	-0.0619	165	164	1.01	0.0000115	1234
Loss of Function	2.19	23	37.5	0.614	0.00000213	366

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000479	0.000479
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000109	0.000109
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000216	0.000211
Middle Eastern	0.000109	0.000109
South Asian	0.000262	0.000261
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+). Controls the rapid response termination and proper regulation of adaptation in olfactory sensory neurons (OSNs) which subsequently influences how odor information is encoded and perceived. May play a role in calcium transport during amelogenesis (By similarity). {ECO:0000250|UniProtKB:Q8CGQ8}.
• Disease: DISEASE: Amelogenesis imperfecta, hypomaturation type, 2A5 (AI2A5) [MIM:615887]: A defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel. {ECO:0000269|PubMed:23375655, ECO:0000269|PubMed:24621671}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Olfactory transduction - Homo sapiens (human);Sodium/Calcium exchangers;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules (Consensus)

Recessive Scores

• pRec: 0.150

Intolerance Scores

• loftool: 0.871
• rvis_EVS: 0.32
• rvis_percentile_EVS: 72.8

Haploinsufficiency Scores

• pHI: 0.155
• hipred: Y
• hipred_score: 0.538
• ghis: 0.500

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.197

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc24a4
• Phenotype: growth/size/body region phenotype; taste/olfaction phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; skeleton phenotype; hematopoietic 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); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype

Gene ontology

• Biological process: ion transport;potassium ion transport;cellular calcium ion homeostasis;sensory perception of smell;sodium ion transmembrane transport;response to stimulus;calcium ion transmembrane transport;amelogenesis
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;membrane
• Molecular function: calcium channel activity;calcium, potassium:sodium antiporter activity;symporter activity