GeneBe

SLC26A4

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

Basic information

Region (hg38): 7:107660828-107717809

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Pendred syndrome; Deafness, autosomal recessive 4, with enlarged vestibular aqueductARAudiologic/Otolaryngologic; EndocrineEarly 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 beneficialAudiologic/Otolaryngologic; Endocrine9398842; 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 (1167 variants)
  • Pendred_syndrome (549 variants)
  • Autosomal_recessive_nonsyndromic_hearing_loss_4 (523 variants)
  • not_specified (172 variants)
  • Rare_genetic_deafness (66 variants)
  • SLC26A4-related_disorder (49 variants)
  • Inborn_genetic_diseases (47 variants)
  • Hearing_loss,_autosomal_recessive (20 variants)
  • Hearing_impairment (17 variants)
  • Deafness (9 variants)
  • Ear_malformation (5 variants)
  • Monogenic_hearing_loss (3 variants)
  • Sensorineural_hearing_loss_disorder (2 variants)
  • Wolff-Parkinson-White_pattern (1 variants)
  • Congenital_hypothyroidism (1 variants)
  • Microcephaly_5,_primary,_autosomal_recessive (1 variants)
  • See_cases (1 variants)
  • Nonsyndromic_genetic_hearing_loss (1 variants)
  • RASopathy (1 variants)
  • Hearing_loss (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. These statistics are base on transcript: NM_000000441.2. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
4
clinvar
14
clinvar
342
clinvar
1
clinvar
 361
missense
64
clinvar
203
clinvar
300
clinvar
25
clinvar
5
clinvar
 597
nonsense
55
clinvar
32
clinvar
1
clinvar
 88
start loss
2
3
 5
frameshift
92
clinvar
77
clinvar
2
clinvar
 171
splice donor/acceptor (+/-2bp)
33
clinvar
68
clinvar
1
clinvar
 102
Total 246 387 318 367 6

Highest pathogenic variant AF is 0.001305661

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SLC26A4protein_codingprotein_codingENST00000265715 2057175
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
8.99e-220.0072212549702511257480.000999
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-2.015284131.280.00002155029
Missense in Polyphen200170.331.17422165
Synonymous-0.2361641601.020.000009071577
Loss of Function0.6623539.50.8860.00000188496

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001830.00182
Ashkenazi Jewish0.00009920.0000992
East Asian0.005670.00567
Finnish0.000.00
European (Non-Finnish)0.0007360.000730
Middle Eastern0.005670.00567
South Asian0.0004250.000425
Other0.0006530.000652

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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