CDX2

protein-coding

caudal type homeobox 2, the group of HOXL subclass homeoboxes

Gene summary

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]

Previous symbols:

CDX3

MANE transcript

NM_001265.6

Inheritance

—

ClinVar variants

P:1U:48B:1

Top phenotype

CDX2-associated caudal anomalies

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr13:27,960,918-27,969,315

External References & Databases

Ensembl (ENSG00000165556)

Transcript & Mutation Effects

hg38 • Region Span ~8.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CDX2 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 44

not providedTotal: 4

CDX2-associated caudal anomaliesTotal: 1

Anorectal malformationTotal: 1

CDX2-related conditionTotal: 1

SirenomeliaTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001265.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense		1 clinvar	47 clinvar			48
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	1	48	1	0	50

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001265.6	RefSeq	NP_001256.4	3	MANE Select
ENST00000381020.8	Ensembl	ENSP00000370408.6	3	MANE Select
NM_001354700.2	RefSeq	NP_001341629.1	3	Standard
ENST00000891171.1	Ensembl	ENSP00000561230.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gastric cancer - Homo sapiens (human)
Vitamin D Receptor Pathway
POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation
Preimplantation Embryo
Developmental Biology

Biological Process

negative regulation of transcription by RNA polymerase II
blood vessel development
trophectodermal cell differentiation
regulation of transcription by RNA polymerase II
transcription by RNA polymerase II

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
RNA polymerase II distal enhancer sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA-binding transcription factor activity

Cellular Component

condensed nuclear chromosome
nucleus
nucleoplasm
transcriptional repressor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000381020
Coding exons: 3
Length: 9003
Individuals with no LoFs: 125489
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125491
p: 0.00000797

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.06	126	164	0.768	0.00000796	1963
Missense (PolyPhen)		20	34.752	0.57551		417
Synonymous	-0.672	83	75.6	1.10	0.00000386	665
Loss of Function	2.46	2	10.7	0.187	4.62e-7	115

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the transcriptional regulation of multiple genes expressed in the intestinal epithelium. Important in broad range of functions from early differentiation to maintenance of the intestinal epithelial lining of both the small and large intestine. Binds preferentially to methylated DNA (PubMed:28473536). {ECO:0000269|PubMed:28473536}.;

Recessive Scores

pRec: 0.551

Intolerance Scores

RVIS EVS: 0.15
RVIS percentile EVS: 64.32

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.737

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium