SLC4A11

solute carrier family 4 member 11, the group of Solute carrier family 4

Basic information

Region (hg38): 20:3227417-3239559

Previous symbols: [ "CHED2", "CDPD1" ]

Links

ENSG00000088836

∙ NCBI:83959 ∙ OMIM:610206 ∙ HGNC:16438 ∙ Uniprot:Q8NBS3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

corneal dystrophy-perceptive deafness syndrome (Strong), mode of inheritance: AR
corneal dystrophy-perceptive deafness syndrome (Supportive), mode of inheritance: AR
Fuchs' endothelial dystrophy (Supportive), mode of inheritance: AD
congenital hereditary endothelial dystrophy of cornea (Supportive), mode of inheritance: AR
corneal dystrophy, Fuchs endothelial, 4 (Limited), mode of inheritance: AD
corneal dystrophy, Fuchs endothelial, 4 (Strong), mode of inheritance: AD
congenital hereditary endothelial dystrophy of cornea (Strong), mode of inheritance: AR
congenital hereditary endothelial dystrophy of cornea (Strong), mode of inheritance: AR
corneal dystrophy-perceptive deafness syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cryohydrocytosis	AD	Hematologic	Individuals with Cryohydrocytosis can suffer from hemolytic anemia, which can be ameliorated by splenectomy, though postsplenectomy thrombotic complications may occur, and awareness may allow surveillance and management	Audiologic/Otolaryngologic; Hematologic; Ophthalmologic	16767101; 16227998; 17220209; 18024964; 20848555; 21203343; 22072594

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC4A11 gene.

not_provided (956 variants)
Corneal_dystrophy-perceptive_deafness_syndrome (222 variants)
Inborn_genetic_diseases (137 variants)
Corneal_dystrophy (80 variants)
Congenital_hereditary_endothelial_dystrophy_of_cornea (67 variants)
Corneal_dystrophy,_Fuchs_endothelial,_4 (52 variants)
not_specified (24 variants)
SLC4A11-related_disorder (20 variants)
Corneal_Dystrophy,_Recessive (1 variants)
Posterior_polymorphous_corneal_dystrophy_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC4A11 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001174089.2. 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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		17 clinvar	443 clinvar	4 clinvar	465
missense	14 clinvar	20 clinvar	204 clinvar	26 clinvar	1 clinvar	265
nonsense	24 clinvar	7 clinvar				31
start loss						0
frameshift	41 clinvar	15 clinvar				56
splice donor/acceptor (+/-2bp)	4 clinvar	31 clinvar	1 clinvar	1 clinvar		37
Total	84	73	222	470	5

Highest pathogenic variant AF is 0.0000749846

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC4A11	protein_coding	protein_coding	ENST00000380059	20	11774

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.64e-15	0.739	125687	0	61	125748	0.000243

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.602	515	555	0.928	0.0000404	5974
Missense in Polyphen		154	213.57	0.72108		2430
Synonymous	-1.69	286	252	1.14	0.0000201	1900
Loss of Function	1.86	29	42.0	0.691	0.00000233	474

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000699	0.000695
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.000598	0.000598
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000256	0.000255
Middle Eastern	0.000598	0.000598
South Asian	0.0000653	0.0000653
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Transporter which plays an important role in sodium- mediated fluid transport in different organs. Prevents severe morphological changes of the cornea caused by increased sodium chloride concentrations in the stroma. In the inner ear, is involved in transport of potassium through the fibrocyte layer to the stria vascularis and is essential for the generation of the endocochlear potential but not for regulation of potassium concentrations in the endolymph. In the kidney, is essential for urinary concentration, mediates a sodium flux into the thin descending limb of Henle loop to allow countercurrent multiplication by osmotic equilibration (By similarity). Involved in borate homeostasis. In the absence of borate, it functions as a Na(+) and OH(-)(H(+)) channel. In the presence of borate functions as an electrogenic Na(+) coupled borate cotransporter. {ECO:0000250|UniProtKB:A2AJN7, ECO:0000269|PubMed:15525507, ECO:0000269|PubMed:25007886}.;
Disease: DISEASE: Corneal dystrophy and perceptive deafness (CDPD) [MIM:217400]: An ocular disease characterized by the association of corneal clouding with progressive perceptive hearing loss. {ECO:0000269|PubMed:17220209}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Corneal endothelial dystrophy (CHED) [MIM:217700]: A congenital corneal dystrophy characterized by thickening and opacification of the cornea, altered morphology of the endothelium, and secretion of an abnormal collagenous layer at the Descemet membrane. {ECO:0000269|PubMed:16767101, ECO:0000269|PubMed:16825429, ECO:0000269|PubMed:17220209, ECO:0000269|PubMed:17397048, ECO:0000269|PubMed:17679935, ECO:0000269|PubMed:18474783, ECO:0000269|PubMed:19369245, ECO:0000269|PubMed:20108384, ECO:0000269|PubMed:20185830, ECO:0000269|PubMed:21203343, ECO:0000269|PubMed:22072594, ECO:0000269|PubMed:26286922}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Corneal dystrophy, Fuchs endothelial, 4 (FECD4) [MIM:613268]: A corneal disease caused by loss of endothelium of the central cornea. It is characterized by focal wart-like guttata that arise from Descemet membrane and develop in the central cornea, epithelial blisters, reduced vision and pain. Descemet membrane is thickened by abnormal collagenous deposition. {ECO:0000269|PubMed:18024964, ECO:0000269|PubMed:20848555, ECO:0000269|PubMed:22072594, ECO:0000269|PubMed:25007886}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.134

Intolerance Scores

loftool: 0.151
rvis_EVS: -2.34
rvis_percentile_EVS: 1.17

Haploinsufficiency Scores

pHI: 0.460
hipred: Y
hipred_score: 0.663
ghis: 0.507

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.251

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Slc4a11
Phenotype: homeostasis/metabolism phenotype; skeleton phenotype; renal/urinary system phenotype; hearing/vestibular/ear phenotype; vision/eye phenotype;

Gene ontology

Biological process: sodium ion transport;bicarbonate transport;cellular cation homeostasis;borate transmembrane transport;sodium ion transmembrane transport;fluid transport;borate transport;regulation of intracellular pH;proton transmembrane transport
Cellular component: integral component of plasma membrane;basolateral plasma membrane
Molecular function: sodium channel activity;inorganic anion exchanger activity;bicarbonate transmembrane transporter activity;proton channel activity;symporter activity;anion:anion antiporter activity;active borate transmembrane transporter activity;protein dimerization activity