CDX2

Chr 13

caudal type homeobox 2

Also known as: CDX-3, CDX2/AS, CDX3

NCBI Gene: 1045ENSG00000165556UniProt: Q99626OMIM: 600297

CDX2 encodes a homeobox transcription factor that regulates intestine-specific genes and is essential for intestinal epithelial development and maintenance. Mutations cause sinoatrial node dysfunction and deafness (autosomal dominant inheritance), presenting with cardiac conduction abnormalities and sensorineural hearing loss. The gene shows moderate constraint to loss-of-function variation (LOEUF 0.589), suggesting some intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.59
Clinical Summary— CDX2
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Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.53) — some intolerance to loss-of-function variants.
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ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 52 VUS of 87 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.529
Z-score 2.46
OE 0.19 (0.07–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.06Z-score
OE missense 0.77 (0.66–0.89)
126 obs / 164.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.07–0.59)
0≤0.351.4
Missense OE0.77 (0.66–0.89)
0≤0.61.4
Synonymous OE1.10
0≤1.21.6
LoF obs/exp: 2 / 10.7Missense obs/exp: 126 / 164.1Syn Z: -0.67
DN
0.5477th %ile
GOF
0.3391th %ile
LOF
0.78top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

87 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic3
VUS52
Likely Benign1
Benign1
Conflicting1
29
Pathogenic
3
Likely Pathogenic
52
VUS
1
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
1
0
2
0
3
VUS
1
45
6
0
52
Likely Benign
0
0
1
0
1
Benign
0
0
1
0
1
Conflicting
—1
Total24539087

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

View in ClinVar →

Protein Context — Lollipop Plot

CDX2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients