GeneBe

SLC4A11

protein-coding

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

Gene summary

This gene encodes a voltage-regulated, electrogenic sodium-coupled borate cotransporter that is essential for borate homeostasis, cell growth and cell proliferation. Mutations in this gene have been associated with a number of endothelial corneal dystrophies including recessive corneal endothelial dystrophy 2, corneal dystrophy and perceptive deafness, and Fuchs endothelial corneal dystrophy. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2010]

Previous symbols:
  • CHED2
  • CDPD1

MANE transcript

NM_001174089.2

Inheritance

AR, AD

ClinVar variants

P:179U:249B:490

Top phenotype

Cryohydrocytosis

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr20:3,227,417-3,239,559

External References & Databases

Ensembl (ENSG00000088836)NCBI Gene (83959)OMIM (610206)HGNC:16438GenCCUniProt (Q8NBS3)AlphaFoldClinVar (SLC4A11)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~12.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital hereditary endothelial dystrophy of corneaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009019

Submitter: Labcorp Genetics (formerly Invitae)

Fuchs' endothelial dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0005321

Submitter: Orphanet

corneal dystrophy-perceptive deafness syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009015

Submitter: Orphanet

congenital hereditary endothelial dystrophy of corneaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009019

Submitter: Orphanet

congenital hereditary endothelial dystrophy of corneaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009019

Submitter: PanelApp Australia

corneal dystrophy, Fuchs endothelial, 4STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0013204

Submitter: PanelApp Australia

corneal dystrophy-perceptive deafness syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009015

Submitter: Natera

corneal dystrophy, Fuchs endothelial, 4STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0013204

Submitter: G2P

corneal dystrophy-perceptive deafness syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009015

Submitter: Labcorp Genetics (formerly Invitae)

corneal dystrophy, Fuchs endothelial, 4LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013204

Submitter: Labcorp Genetics (formerly Invitae)

congenital hereditary endothelial dystrophy of corneaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009019

Submitter: G2P

corneal dystrophy, Fuchs endothelial, 4LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0013204

Submitter: Natera

Clinical Genomic Database (CGD)

CryohydrocytosisAD

Manifestation: Audiologic/Otolaryngologic; Hematologic; Ophthalmologic

Intervention: Hematologic

Rationale: 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

Refs: 16767101; 16227998; 17220209; 18024964; 20848555; 21203343; 22072594Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC4A11 variants in ClinVar

9 Conditions Cataloged
not providedTotal: 995
Corneal dystrophy-perceptive deafness syndromeTotal: 265
Inborn genetic diseasesTotal: 148
not specifiedTotal: 98
Corneal dystrophyTotal: 82
SLC4A11-related disorderTotal: 77
Congenital hereditary endothelial dystrophy of corneaTotal: 73
Corneal dystrophy, Fuchs endothelial, 4Total: 55

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001174089.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
17
clinvar
454
clinvar
3
clinvar
 474
missense
7
clinvar
27
clinvar
232
clinvar
30
clinvar
2
clinvar
 298
nonsense
20
clinvar
16
clinvar
 36
start loss
0
frameshift
36
clinvar
32
clinvar
 68
splice donor/acceptor (+/-2bp)
7
clinvar
34
clinvar
1
clinvar
 42
Total701092494855918

Highest pathogenic variant AF is 0.00007498463

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001174089.2RefSeqNP_001167560.120MANE Select
ENST00000642402.1EnsemblENSP00000493503.120MANE Select
NM_001174090.2RefSeqNP_001167561.120Standard
NM_001363745.2RefSeqNP_001350674.119Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • sodium ion transport
  • bicarbonate transport
  • cellular cation homeostasis
  • borate transmembrane transport
  • sodium ion transmembrane transport

Molecular Function

  • sodium channel activity
  • inorganic anion exchanger activity
  • bicarbonate transmembrane transporter activity
  • proton channel activity
  • symporter activity

Cellular Component

  • integral component of plasma membrane
  • basolateral plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000380059
Coding exons
20
Length
11774
Individuals with no LoFs
125687
Homozygous LoFs
0
Heterozygous LoFs
61
Defined
125748
p
0.000243
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.6025155550.9280.00004045974
Missense (PolyPhen)154213.570.721082430
Synonymous-1.692862521.140.00002011900
Loss of Function1.862942.00.6910.00000233474

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000500.00049rare
Latino/Admixed American0.000200.00020rare
Ashkenazi Jewish0.000100.000099rare
East Asian0.000600.00060rare
Finnish0.0000930.000092rare
European (Non-Finnish)0.000260.00025rare
South Asian0.0000650.000065rare
Other0.000160.00016rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.251

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.