SLC22A4

solute carrier family 22 member 4, the group of Solute carrier family 22

Basic information

Region (hg38): 5:132294393-132344190

Previous symbols: [ "DFNB60" ]

Links

ENSG00000197208 ∙ NCBI:6583 ∙ OMIM:604190 ∙ HGNC:10968 ∙ Uniprot:Q9H015 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC22A4 gene.

• not provided (80 variants)
• Inborn genetic diseases (14 variants)
• SLC22A4-related condition (5 variants)
• not specified (3 variants)
• Hereditary hearing loss and deafness (1 variants)
• SLC22A4 POLYMORPHISM (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC22A4 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			2	21	6	29
missense			41		3	44
nonsense						0
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region				2	2	4
non coding				5	10	15
Total	0	0	46	26	19

Variants in SLC22A4

This is a list of pathogenic ClinVar variants found in the SLC22A4 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-132294607-A-T		SLC22A4-related disorder	Likely benign (Apr 24, 2019)
5-132294647-C-T			Likely benign (Apr 08, 2022)
5-132294659-G-A			Uncertain significance (Jan 12, 2024)
5-132294694-C-T			Likely benign (Sep 23, 2022)
5-132294711-A-G			Uncertain significance (Jul 25, 2022)
5-132294750-C-T			Uncertain significance (Mar 04, 2022)
5-132294754-G-A			Likely benign (Aug 31, 2018)
5-132294774-C-G		not specified	Uncertain significance (Sep 26, 2023)
5-132294775-G-C			Likely benign (Nov 19, 2022)
5-132294778-C-T			Likely benign (Sep 28, 2018)
5-132294797-G-A		not specified	Uncertain significance (Jan 15, 2024)
5-132294814-TGTCCCGCTGCGGCTGC-T			Uncertain significance (Mar 09, 2023)
5-132294825-G-C		not specified	Uncertain significance (Jul 14, 2021)
5-132294825-G-T			Uncertain significance (Jun 07, 2023)
5-132294832-G-C			Likely benign (Mar 09, 2023)
5-132294834-A-G		not specified	Uncertain significance (Jul 11, 2023)
5-132294841-C-T			Uncertain significance (Feb 09, 2022)
5-132294880-C-T			Likely benign (Jan 25, 2024)
5-132294883-C-T			Likely benign (Nov 28, 2021)
5-132294901-C-T			Likely benign (Aug 31, 2023)
5-132294902-G-C		not specified	Uncertain significance (Mar 01, 2024)
5-132294909-AG-A			Uncertain significance (Jul 04, 2021)
5-132294929-C-G		not specified	Uncertain significance (Sep 06, 2022)
5-132294954-G-A		Hereditary hearing loss and deafness	Uncertain significance (Jul 10, 2023)
5-132294955-C-T			Benign/Likely benign (Dec 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC22A4	protein_coding	protein_coding	ENST00000200652	10	49764

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.83e-8	0.864	125651	0	97	125748	0.000386

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.852	259	301	0.862	0.0000158	3553
Missense in Polyphen		57	65.647	0.86828		800
Synonymous	-1.11	140	124	1.13	0.00000678	1162
Loss of Function	1.64	16	24.8	0.644	0.00000126	266

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000860	0.000843
Ashkenazi Jewish	0.00	0.00
East Asian	0.000653	0.000653
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000292	0.000290
Middle Eastern	0.000653	0.000653
South Asian	0.000915	0.000915
Other	0.000654	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 1.78. A key substrate of this transporter seems to be ergothioneine (ET). {ECO:0000269|PubMed:10215651, ECO:0000269|PubMed:15795384}.
• Disease: DISEASE: Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. {ECO:0000269|PubMed:14608356}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Choline metabolism in cancer - Homo sapiens (human);Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Organic cation transport;Organic cation/anion/zwitterion transport (Consensus)

Recessive Scores

• pRec: 0.102

Intolerance Scores

• loftool: 0.538
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.57

Haploinsufficiency Scores

• pHI: 0.0720
• hipred: N
• hipred_score: 0.312
• ghis: 0.550

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0217

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc22a4
• Phenotype: homeostasis/metabolism phenotype; immune system phenotype; digestive/alimentary 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)

Gene ontology

• Biological process: triglyceride metabolic process;sodium ion transport;body fluid secretion;carnitine metabolic process;organic cation transport;quaternary ammonium group transport;carnitine transport;carnitine transmembrane transport
• Cellular component: mitochondrion;plasma membrane;integral component of plasma membrane;apical plasma membrane
• Molecular function: nucleotide binding;protein binding;ATP binding;secondary active organic cation transmembrane transporter activity;carnitine transmembrane transporter activity;symporter activity;cation:cation antiporter activity;quaternary ammonium group transmembrane transporter activity;PDZ domain binding