corneal dystrophy, Fuchs endothelial, 4

Summary

corneal dystrophy, Fuchs endothelial, 4 (MONDO:0013204) is a disease caused by SLC4A11 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SLC4A11 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 53

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	corneal dystrophy, Fuchs endothelial, 4
Mondo ID	MONDO:0013204
MeSH	C567677
OMIM	613268
UMLS	C2750450
MedGen	413309
GARD	0018219
Is cancer (heuristic)	no

Also known as: corneal dystrophy, Fuchs endothelial, 4 · corneal dystrophy, Fuchs endothelial, type 4 · FECD4 · Fuchs’ endothelial dystrophy caused by mutation in SLC4A11 · SLC4A11 Fuchs’ endothelial dystrophy

Data availability: 53 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › corneal disorder › corneal dystrophy › corneal endothelial dystrophy › Fuchs’ endothelial dystrophy › corneal dystrophy, Fuchs endothelial, 4

Related subtypes (7): corneal dystrophy, Fuchs endothelial, 1, corneal dystrophy, fuchs endothelial, 2, corneal dystrophy, Fuchs endothelial, 3, corneal dystrophy, fuchs endothelial, 5, corneal dystrophy, Fuchs endothelial, 6, corneal dystrophy, fuchs endothelial, 7, corneal dystrophy, Fuchs endothelial, 8

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

53 retrieved; paginated sample, class counts are floors:

17 likely pathogenic, 12 uncertain significance, 11 pathogenic/likely pathogenic, 8 pathogenic, 5 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066524	NM_001174089.2(SLC4A11):c.2306_2307del (p.Tyr769fs)	SLC4A11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072511	NM_001174089.2(SLC4A11):c.425_432dup (p.Arg145fs)	SLC4A11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1307	NM_001174089.2(SLC4A11):c.1765C>T (p.Arg589Ter)	SLC4A11	Pathogenic	criteria provided, multiple submitters, no conflicts
1311	NM_001174089.2(SLC4A11):c.2558G>A (p.Arg853His)	SLC4A11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1316	NM_001174089.2(SLC4A11):c.2480T>C (p.Leu827Pro)	SLC4A11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322	NM_001174089.2(SLC4A11):c.51_52del (p.Pro18fs)	SLC4A11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1356826	NM_001174089.2(SLC4A11):c.2185_2192dup (p.Ile732fs)	SLC4A11	Pathogenic	criteria provided, multiple submitters, no conflicts
1453845	NM_001174089.2(SLC4A11):c.1282+1G>A	SLC4A11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1504281	NM_001174089.2(SLC4A11):c.2558+1G>A	SLC4A11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208613	NM_001174089.2(SLC4A11):c.425_433delinsC (p.Arg142fs)	SLC4A11	Pathogenic	criteria provided, multiple submitters, no conflicts
2803216	NM_001174089.2(SLC4A11):c.2140del (p.Arg714fs)	SLC4A11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4531751	NM_001174089.2(SLC4A11):c.2394_2412del (p.Tyr799fs)	SLC4A11	Pathogenic	criteria provided, single submitter
649470	NM_001174089.2(SLC4A11):c.2215C>T (p.Arg739Trp)	SLC4A11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
664579	NM_001174089.2(SLC4A11):c.2158G>T (p.Glu720Ter)	SLC4A11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
666996	NM_001174089.2(SLC4A11):c.1110C>A (p.Cys370Ter)	SLC4A11	Pathogenic	criteria provided, multiple submitters, no conflicts
855486	NM_001174089.2(SLC4A11):c.2192+1G>A	SLC4A11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
855644	NM_001174089.2(SLC4A11):c.764C>T (p.Thr255Met)	SLC4A11	Pathogenic	criteria provided, multiple submitters, no conflicts
941893	NM_001174089.2(SLC4A11):c.62C>A (p.Ser21Ter)	SLC4A11	Pathogenic	criteria provided, multiple submitters, no conflicts
962167	NM_001174089.2(SLC4A11):c.2140C>T (p.Arg714Ter)	SLC4A11	Pathogenic	criteria provided, multiple submitters, no conflicts
1068021	NM_001174089.2(SLC4A11):c.1201G>A (p.Gly401Arg)	SLC4A11	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068065	NM_001174089.2(SLC4A11):c.1201G>C (p.Gly401Arg)	SLC4A11	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1315	NM_001174089.2(SLC4A11):c.2518A>G (p.Met840Val)	SLC4A11	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1320	NM_001174089.2(SLC4A11):c.2078G>A (p.Gly693Glu)	SLC4A11	Likely pathogenic	criteria provided, single submitter
1466008	NM_001174089.2(SLC4A11):c.291+1G>T	SLC4A11	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1485387	NM_001174089.2(SLC4A11):c.2193-12_2201del	SLC4A11	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2138323	NM_001174089.2(SLC4A11):c.2363G>A (p.Arg788His)	SLC4A11	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2816941	NM_001174089.2(SLC4A11):c.730-2A>C	SLC4A11	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3587183	NM_001174089.2(SLC4A11):c.2147dup (p.Ala717fs)	SLC4A11	Likely pathogenic	criteria provided, single submitter
3587185	NM_001174089.2(SLC4A11):c.1897C>T (p.Gln633Ter)	SLC4A11	Likely pathogenic	criteria provided, single submitter
3587186	NM_001174089.2(SLC4A11):c.1554dup (p.Val519fs)	SLC4A11	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SLC4A11	Strong	Autosomal recessive	corneal dystrophy-perceptive deafness syndrome	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC4A11	Orphanet:1490	Corneal dystrophy-perceptive deafness syndrome
SLC4A11	Orphanet:293603	Congenital hereditary endothelial dystrophy type II
SLC4A11	Orphanet:98974	Fuchs endothelial corneal dystrophy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC4A11	HGNC:16438	ENSG00000088836	Q8NBS3	Solute carrier family 4 member 11	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC4A11	Solute carrier family 4 member 11	Multifunctional transporter with an impact in cell morphology and differentiation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC4A11	Other/Unknown	no		HCO3_transpt_euk, HCO3_transpt-like_TM_dom, PTrfase/Anion_transptr

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
metanephros cortex	1
nasal cavity epithelium	1
olfactory segment of nasal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC4A11	197	broad	marker	nasal cavity epithelium, olfactory segment of nasal mucosa, metanephros cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC4A11	846

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC4A11	Q8NBS3	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
borate transport	1	16852.0×	8e-04	SLC4A11
fluid transport	1	5617.3×	0.001	SLC4A11
regulation of mesenchymal stem cell differentiation	1	4213.0×	0.001	SLC4A11
monoatomic ion homeostasis	1	2407.4×	0.001	SLC4A11
monoatomic anion transport	1	1404.3×	0.002	SLC4A11
cellular hypotonic response	1	1404.3×	0.002	SLC4A11
intracellular monoatomic cation homeostasis	1	1123.5×	0.002	SLC4A11
bicarbonate transport	1	802.5×	0.002	SLC4A11
regulation of mitochondrial membrane potential	1	543.6×	0.003	SLC4A11
proton transmembrane transport	1	312.1×	0.004	SLC4A11
sodium ion transport	1	271.8×	0.004	SLC4A11
transmembrane transport	1	168.5×	0.006	SLC4A11
cellular response to oxidative stress	1	154.6×	0.006	SLC4A11

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC4A11	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SLC4A11

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC4A11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.