CDX2

Chr 13

caudal type homeobox 2

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

NCBI Gene: 1045 ENSG00000165556 UniProt: Q99626

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.

ResearchSummary from RefSeq, UniProt

This gene is a member of the caudal-related homeobox transcription factor gene family. The encoded protein is a major regulator of intestine-specific genes involved in cell growth an differentiation. This protein also plays a role in early embryonic development of the intestinal tract. Aberrant expression of this gene is associated with intestinal inflammation and tumorigenesis. [provided by RefSeq, Jan 2012]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

399

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.59

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.19 (0.07–0.59)

0≤0.351.4

Missense OE?0.77 (0.66–0.89)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 2 / 10.7Missense obs/exp: 126 / 164.1Syn Z: -0.67

Background carrier burden — how many people carry a rare variant somewhere in CDX2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

400 rare PASS variants

Rare truncating (LoF)

1 in 7,800

18 rare PASS variants

Rare synonymous (reference)

1 in 230

239 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CDX2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 11,000
South Asian	~43k	1 in 140	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 180	1 in 4,300
European (Finnish)	~27k	1 in 440	1 in 1,200
Admixed American	~22k	1 in 210	≈ 1 in 20,000
African / African American	~21k	1 in 190	≈ 1 in 21,000
East Asian	~20k	1 in 180	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 960	none seen
Middle Eastern	~2,884	1 in 150	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓