CLDND1

Chr 3

claudin domain containing 1

Also known as: C3orf4, CLDN-25, GENX-3745, Z38

NCBI Gene: 56650 ENSG00000080822 UniProt: Q9NY35 OMIM: 619677

The protein negatively regulates cellular permeability to small molecules at the cell surface. Mutations cause autosomal recessive deafness-90, which presents as hearing loss. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.617), suggesting some intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

Located in cell surface. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.62

Clinical Summary— CLDND1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

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ClinVar Variants

42 VUS of 46 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.164

Z-score 2.61

OE 0.27 (0.13–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.09Z-score

OE missense 0.98 (0.86–1.12)

155 obs / 158.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.13–0.62)

0≤0.351.4

Missense OE?0.98 (0.86–1.12)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 4 / 14.8Missense obs/exp: 155 / 158.2Syn Z: -0.47

ClinVar Variant Classifications

46 submitted variants in ClinVar

ClinVar

Classification Summary

VUS42

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	42	42
Likely Benign	0	0
Benign	0	0
Total	42	42

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap CLDND1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →