CDX1

protein-coding

caudal type homeobox 1, the group of HOXL subclass homeoboxes

Gene summary

This gene is a member of the caudal-related homeobox transcription factor gene family. The encoded DNA-binding protein regulates intestine-specific gene expression and enterocyte differentiation. It has been shown to induce expression of the intestinal alkaline phosphatase gene, and inhibit beta-catenin/T-cell factor transcriptional activity. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001804.3

Inheritance

—

ClinVar variants

U:54B:2

Top phenotype

CDX1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr5:150,166,778-150,184,558

External References & Databases

Ensembl (ENSG00000113722)

Transcript & Mutation Effects

hg38 • Region Span ~17.8 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 CDX1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 54

CDX1-related disorderTotal: 2

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001804.3. 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			54 clinvar	1 clinvar		55
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	54	2	0	56

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001804.3	RefSeq	NP_001795.2	3	MANE Select
ENST00000231656.13	Ensembl	ENSP00000231656.7	3	MANE Select
ENST00001025487.1	Ensembl	ENSP00000695304.1	4	Standard
ENST00001025488.1	Ensembl	ENSP00000695305.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cdx1b	Danio rerio	Structure: intestinal epithelial cell Quality: cuboid abnormal

Gene / Model

Organism

Observed Phenotype

cdx1b

Danio rerio

Structure: intestinal epithelial cell

Quality: cuboid

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of nuclear beta catenin signaling and target gene transcription

Biological Process

regulation of transcription by RNA polymerase II
animal organ morphogenesis
anterior/posterior axis specification
anterior/posterior pattern specification
regulation of somitogenesis

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 activator activity, RNA polymerase II-specific
DNA-binding transcription factor activity

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000231656
Coding exons: 3
Length: 17763
Individuals with no LoFs: 125418
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125420
p: 0.00000797

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0641	99	101	0.982	0.00000684	1613
Missense (PolyPhen)		39	46.038	0.84713		691
Synonymous	0.765	37	43.4	0.852	0.00000276	579
Loss of Function	1.46	2	5.80	0.345	2.49e-7	94

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000068	0.000062	rare
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)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in transcriptional regulation (PubMed:24623306). Involved in activated KRAS-mediated transcriptional activation of PRKD1 in colorectal cancer (CRC) cells (PubMed:24623306). Binds to the PRKD1 promoter in colorectal cancer (CRC) cells (PubMed:24623306). Could play a role in the terminal differentiation of the intestine. Binds preferentially to methylated DNA (PubMed:28473536). {ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:28473536}.;

Recessive Scores

pRec: 0.196

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00721

Gene Damage Prediction

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