SLC4A11

Chr 20AR

solute carrier family 4 member 11

Also known as: BTR1, CDPD1, CHED, CHED2, NABC1, dJ794I6.2

NCBI Gene: 83959ENSG00000088836UniProt: Q8NBS3

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]

Primary Disease Associations & Inheritance

Corneal dystrophy, Fuchs endothelial, 4MIM #613268
Corneal endothelial dystrophy and perceptive deafnessMIM #217400
AR
Corneal endothelial dystrophy, autosomal recessiveMIM #217700
AR
UniProtCorneal dystrophy and perceptive deafness
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC4A11
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.94LOEUF
pLI 0.000
Z-score 1.86
OE 0.69 (0.51–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.60Z-score
OE missense 0.93 (0.86–1.00)
515 obs / 554.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.69 (0.51–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.86–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.14
0≤1.21.6
LoF obs/exp: 29 / 42.0Missense obs/exp: 515 / 554.9Syn Z: -1.69

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SLC4A11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SLC4A11-related corneal endothelial dystrophy with or without deafness

strong
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

SLC4A11-related corneal dystrophy, Fuchs endothelial

strong
ADUndeterminedUncertain
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Corneal dystrophy, Fuchs endothelial, 4

MIM #613268

Molecular basis of disorder known

Corneal endothelial dystrophy and perceptive deafness

MIM #217400

Molecular basis of disorder known

Autosomal recessive

Corneal endothelial dystrophy, autosomal recessive

MIM #217700

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SLC4A11
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Corneal dystrophies.
Klintworth GK·Orphanet J Rare Dis
2009Review
SLC4A11 and the Pathophysiology of Congenital Hereditary Endothelial Dystrophy.
Patel SP et al.·Biomed Res Int
2015Review
SLC4A11 mediates ammonia import and promotes cancer stemness in hepatocellular carcinoma.
Elaimy AL et al.·JCI Insight
2024
SLC4A11 Revisited: Isoforms, Expression, Functions, and Unresolved Questions.
Kovaleva PA et al.·Biomolecules
2025Review
Homeostasis of SLC4A11 protein is mediated by endoplasmic reticulum-associated degradation.
Hara S et al.·Exp Eye Res
2019
Harboyan Syndrome: A Novel SLC4A11 Variant With Unique Genotype-Phenotype Correlation.
Magan T et al.·Cornea
2022Case report
Pathogenicity and Function Analysis of Two Novel SLC4A11 Variants in Patients With Congenital Hereditary Endothelial Dystrophy.
Zhen T et al.·Transl Vis Sci Technol
2023Cohort
Homozygous SLC4A11 mutation in a large Irish CHED2 pedigree.
Hand CK et al.·Ophthalmic Genet
2017
Harboyan syndrome: novel SLC4A11 mutation, clinical manifestations, and outcome of corneal transplantation.
Tananuvat N et al.·J Hum Genet
2021Case report
Corneal dystrophy mutations R125H and R804H disable SLC4A11 by altering the extracellular pH dependence of the intracellular pK that governs H(+)(OH(-)) transport.
Quade BN et al.·Am J Physiol Cell Physiol
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools