SLC26A4

solute carrier family 26 member 4, the group of Solute carrier family 26

Basic information

Region (hg38): 7:107660827-107717809

Previous symbols: [ "DFNB4" ]

Links

ENSG00000091137 ∙ NCBI:5172 ∙ OMIM:605646 ∙ HGNC:8818 ∙ Uniprot:O43511 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 4 (Strong), mode of inheritance: AR
• Pendred syndrome (Supportive), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• athyreosis (Supportive), mode of inheritance: AD
• thyroid hypoplasia (Supportive), mode of inheritance: AD
• autosomal recessive nonsyndromic hearing loss 4 (Definitive), mode of inheritance: AR
• Pendred syndrome (Definitive), mode of inheritance: AR
• Pendred syndrome (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 4 (Strong), mode of inheritance: AR
• Pendred syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pendred syndrome; Deafness, autosomal recessive 4, with enlarged vestibular aqueduct	AR	Audiologic/Otolaryngologic; Endocrine	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Pendred syndrome, surveillance for and treatment of thyroid abnormalities can be beneficial	Audiologic/Otolaryngologic; Endocrine	9398842; 9500541; 9920104; 10190331; 10902795; 11317356; 14508505; 15689455; 16570074; 17690912; 17503324; 19426954; 21488278; 20301640
Promoter variants have been reported as causative; Digenic inheritance (with KCNJ10) has been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC26A4 gene.

• not provided (944 variants)
• Pendred syndrome (443 variants)
• Autosomal recessive nonsyndromic hearing loss 4 (382 variants)
• not specified (148 variants)
• Rare genetic deafness (63 variants)
• Autosomal recessive nonsyndromic hearing loss 4;Pendred syndrome (41 variants)
• Inborn genetic diseases (24 variants)
• Pendred syndrome;Autosomal recessive nonsyndromic hearing loss 4 (24 variants)
• SLC26A4-Related Disorders (13 variants)
• Hearing impairment (13 variants)
• Hearing loss, autosomal recessive (12 variants)
• SLC26A4-related condition (8 variants)
• SLC26A4-related disorder (3 variants)
• Nonsyndromic Hearing Loss, Recessive (3 variants)
• Ear malformation (3 variants)
• Deafness (1 variants)
• Microcephaly 5, primary, autosomal recessive (1 variants)
• Hypothyroidism (1 variants)
• - (1 variants)
• Hearing loss (1 variants)
• Wolff-Parkinson-White pattern (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC26A4 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		1	4	272	1	278
missense	35	105	176	11	3	330
nonsense	33	29	1			63
start loss	1	2				3
frameshift	52	55	2			109
inframe indel	2	3	8			13
splice donor/acceptor (+/-2bp)	22	46	1			69
splice region	3	6	14	55	2	80
non coding		1	56	113	39	209
Total	145	242	248	396	43

Highest pathogenic variant AF is 0.000828

Variants in SLC26A4

This is a list of pathogenic ClinVar variants found in the SLC26A4 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-107660851-G-A		Pendred syndrome • Autosomal recessive nonsyndromic hearing loss 4	Uncertain significance (Sep 05, 2021)
7-107660860-G-A		Rare genetic deafness • not specified • Autosomal recessive nonsyndromic hearing loss 4	Conflicting classifications of pathogenicity (Mar 24, 2023)
7-107660945-T-G			Benign (Dec 10, 2018)
7-107661378-C-T			Likely benign (Dec 24, 2018)
7-107661444-C-T			Likely benign (Dec 22, 2018)
7-107661524-A-AG			Likely benign (Jul 22, 2020)
7-107661637-A-G		Autosomal recessive nonsyndromic hearing loss 4;Pendred syndrome • Pendred syndrome • Rare genetic deafness • Autosomal recessive nonsyndromic hearing loss 4 • SLC26A4-related disorder	Pathogenic/Likely pathogenic (Jan 29, 2024)
7-107661643-T-C		Rare genetic deafness • Pendred syndrome • Autosomal recessive nonsyndromic hearing loss 4 • SLC26A4-related disorder	Pathogenic (Jan 30, 2024)
7-107661643-T-G			Pathogenic/Likely pathogenic (Mar 22, 2023)
7-107661644-G-A		Autosomal recessive nonsyndromic hearing loss 4	Pathogenic (-)
7-107661644-G-C		Pendred syndrome	Pathogenic/Likely pathogenic (Aug 01, 2023)
7-107661650-G-A			Likely benign (Jun 09, 2023)
7-107661650-G-T			Likely benign (Sep 23, 2023)
7-107661656-C-A		not specified • Pendred syndrome • Autosomal recessive nonsyndromic hearing loss 4	Conflicting classifications of pathogenicity (Jan 31, 2024)
7-107661656-C-T			Likely benign (Mar 18, 2023)
7-107661658-G-T		not specified • Pendred syndrome • Autosomal recessive nonsyndromic hearing loss 4	Conflicting classifications of pathogenicity (Jan 27, 2024)
7-107661662-G-A			Likely benign (Jan 02, 2024)
7-107661665-G-A			Likely benign (Mar 12, 2022)
7-107661666-G-A			Uncertain significance (Feb 21, 2023)
7-107661666-G-T			Pathogenic (May 11, 2020)
7-107661668-G-A			Likely benign (May 22, 2023)
7-107661669-C-A		Pendred syndrome • Autosomal recessive nonsyndromic hearing loss 4 • SLC26A4-related disorder	Conflicting classifications of pathogenicity (Jan 16, 2024)
7-107661674-G-A			Likely benign (Mar 15, 2021)
7-107661674-G-T			Likely benign (Apr 20, 2023)
7-107661677-G-A			Likely benign (Mar 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC26A4	protein_coding	protein_coding	ENST00000265715	20	57175

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.99e-22	0.00722	125497	0	251	125748	0.000999

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.01	528	413	1.28	0.0000215	5029
Missense in Polyphen		200	170.33	1.1742		2165
Synonymous	-0.236	164	160	1.02	0.00000907	1577
Loss of Function	0.662	35	39.5	0.886	0.00000188	496

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00183	0.00182
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00567	0.00567
Finnish	0.00	0.00
European (Non-Finnish)	0.000736	0.000730
Middle Eastern	0.00567	0.00567
South Asian	0.000425	0.000425
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Sodium-independent transporter of chloride and iodide. {ECO:0000269|PubMed:10192399}.
• Disease: DISEASE: Deafness, autosomal recessive, 4 (DFNB4) [MIM:600791]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB4 is associated with an enlarged vestibular aqueduct. {ECO:0000269|PubMed:10190331, ECO:0000269|PubMed:10700480, ECO:0000269|PubMed:11748854, ECO:0000269|PubMed:12676893, ECO:0000269|PubMed:14508505, ECO:0000269|PubMed:14679580, ECO:0000269|PubMed:19204907, ECO:0000269|PubMed:20108392, ECO:0000269|PubMed:20597900, ECO:0000269|PubMed:24051746, ECO:0000269|PubMed:28281779, ECO:0000269|PubMed:9500541}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thyroid hormone synthesis - Homo sapiens (human);Tyrosine metabolism;Biopterin metabolism;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Multifunctional anion exchangers (Consensus)

Recessive Scores

• pRec: 0.439

Intolerance Scores

• loftool: 0.0893
• rvis_EVS: 1.14
• rvis_percentile_EVS: 92.34

Haploinsufficiency Scores

• pHI: 0.512
• hipred: N
• hipred_score: 0.353
• ghis: 0.468

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.192

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc26a4
• Phenotype: reproductive system phenotype; pigmentation phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; renal/urinary system phenotype; hearing/vestibular/ear phenotype; 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); digestive/alimentary phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: ion transport;regulation of pH;sensory perception of sound;sulfate transport;inorganic anion transport;bicarbonate transport;iodide transport;oxalate transport;regulation of protein localization;sulfate transmembrane transport;chloride transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;apical plasma membrane;brush border membrane;extracellular exosome
• Molecular function: secondary active sulfate transmembrane transporter activity;bicarbonate transmembrane transporter activity;chloride transmembrane transporter activity;iodide transmembrane transporter activity;sulfate transmembrane transporter activity;anion:anion antiporter activity;oxalate transmembrane transporter activity