CLDN19

Chr 1AR

claudin 19

Also known as: HOMG5

NCBI Gene: 149461ENSG00000164007UniProt: Q8N6F1

The product of this gene belongs to the claudin family. It plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Defects in this gene are the cause of hypomagnesemia renal with ocular involvement (HOMGO). HOMGO is a progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis associated with severe ocular abnormalities such as bilateral chorioretinal scars, macular colobomata, significant myopia and nystagmus. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2010]

Primary Disease Associations & Inheritance

Hypomagnesemia 5, renal, with ocular involvementMIM #248190
AR
225
ClinVar variants
37
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CLDN19
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
37 Pathogenic / Likely Pathogenic· 115 VUS of 225 total submissions

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.
1.08LOEUF
pLI 0.005
Z-score 1.40
OE 0.51 (0.27–1.08)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.78Z-score
OE missense 0.81 (0.70–0.95)
112 obs / 137.7 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.0.51 (0.27–1.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.70–0.95)
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.0.77
0≤1.21.6
LoF obs/exp: 5 / 9.7Missense obs/exp: 112 / 137.7Syn Z: 1.46

ClinVar Variant Classifications

225 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic19
VUS115
Likely Benign52
Benign14
Conflicting7
18
Pathogenic
19
Likely Pathogenic
115
VUS
52
Likely Benign
14
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
3
13
0
18
Likely Pathogenic
5
10
4
0
19
VUS
3
65
45
2
115
Likely Benign
0
9
23
20
52
Benign
0
3
11
0
14
Conflicting
—7
Total10909622225

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CLDN19 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CLDN19-related hypomagnesemia with ocular involvement

definitive
ARUndeterminedUncertain
Dev. DisordersEye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
CLAUDIN 19; CLDN19
MIM #610036 · *

Hypomagnesemia 5, renal, with ocular involvement

MIM #248190

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
Vall-Palomar M et al.·Pediatr Nephrol
2021Review
Claudins in Renal Physiology and Pathology.
Prot-Bertoye C et al.·Genes (Basel)
2020Review
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: phenotype-genotype correlation and outcome in 32 patients with CLDN16 or CLDN19 mutations.
Godron A et al.·Clin J Am Soc Nephrol
2012Cohort
Mutation in the tight-junction gene claudin 19 (CLDN19) and familial hypomagnesemia, hypercalciuria, nephrocalcinosis (FHHNC) and severe ocular disease.
Naeem M et al.·Am J Nephrol
2011Case report
Further evidence that a specific homozygous CLDN19 variant results in non-syndromic maculopathy and can be mistaken for prior ocular toxoplasmosis infection.
Khan AO·Ophthalmic Genet
2025
Genetic causes of hypomagnesemia, a clinical overview.
Viering DHHM et al.·Pediatr Nephrol
2017Review
Familial non-syndromic macular pseudocoloboma secondary to homozygous CLDN19 mutation.
Khan AO et al.·Ophthalmic Genet
2018Case report
Claudin-19 mutations and clinical phenotype in Spanish patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
Claverie-Martín F et al.·PLoS One
2013Cohort
Heterogeneity is a common ground in familial hypomagnesemia with hypercalciuria and nephrocalcinosis caused by CLDN19 gene mutations.
Vall-Palomar M et al.·J Nephrol
2021
Renal, ocular, and neuromuscular involvements in patients with CLDN19 mutations.
Faguer S et al.·Clin J Am Soc Nephrol
2011Cohort
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