CDX4

Summary

CDX4 (caudal type homeobox 4, HGNC:1808) is a protein-coding gene on chromosome Xq13.2, encoding Homeobox protein CDX-4 (O14627).

This gene encodes a member of a small subfamily of homeobox containing transcription factors. The encoded protein may regulate homeobox gene expression during anteroposterior patterning and hematopoiesis.

Source: NCBI Gene 1046 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_005193

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1808
Approved symbol	CDX4
Name	caudal type homeobox 4
Location	Xq13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000131264
Ensembl biotype	protein_coding
OMIM	300025
Entrez	1046

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000373514, ENST00000911265

RefSeq mRNA: 1 — MANE Select: NM_005193 NM_005193

CCDS: CCDS14424

Canonical transcript exons

ENST00000373514 — 3 exons

Exon	Start	End
ENSE00000899053	73453517	73453662
ENSE00001460735	73454379	73455171
ENSE00001460739	73447053	73447755

Expression profiles

Bgee: expression breadth tissue_specific, 9 present calls, max score 63.49.

Top tissues by expression

275 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tongue squamous epithelium	UBERON:0006919	63.49	gold quality
diaphragm	UBERON:0001103	60.13	gold quality
skin of abdomen	UBERON:0001416	51.49	gold quality
deltoid	UBERON:0001476	50.81	gold quality
quadriceps femoris	UBERON:0001377	50.69	gold quality
hair follicle	UBERON:0002073	50.54	gold quality
vastus lateralis	UBERON:0001379	50.32	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
oviduct epithelium	UBERON:0004804	49.19	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
epithelial cell of pancreas	CL:0000083	48.45	gold quality
cervix epithelium	UBERON:0004801	48.39	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
zone of skin	UBERON:0000014	47.57	gold quality
metanephric glomerulus	UBERON:0004736	47.45	gold quality
thymus	UBERON:0002370	47.42	gold quality
kidney epithelium	UBERON:0004819	47.39	gold quality
nephron tubule	UBERON:0001231	47.30	gold quality
skeletal muscle tissue	UBERON:0001134	47.10	gold quality
gluteal muscle	UBERON:0002000	47.03	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	46.62	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.30

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
CDX4	Activation
HOXA10
HOXA9	Unknown
INS

JASPAR motifs

Motif	Name	Family
MA1473.1	CDX4	HOX
MA1473.2	CDX4	HOX

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): CDX1, CDX2, CDX4, CTNNB1, HNF4A, HOXA10, LEF1, POU2F1, TBPL2

Literature-anchored findings (GeneRIF, showing 5)

• positive feedback relationship between HoxA10 and Cdx4, which potentially amplified the contribution of either transcription factor to the pathogenesis of AML. (PMID:21471217)
• Expression of CDX1 and CDX4 is not correlated with the pathogenesis and relapse of adult ALL. (PMID:21518475)
• CDX4 gene was introduced to reprogram adipose tissue derived mesenchymal stem cells to differentiate along the hematopoietic lineage. (PMID:22721648)
• a molecular mechanisms through which increased expression of HoxA10 increases Cdx4 expression by direct CDX4 activation and by Fgf2-induced beta-catenin activity. This results in Cdx4-induced HoxA10-expression, creating a positive feedback mechanism (PMID:23038246)
• Gene expression analyses on WNT-dependent KDR(+)CD235a(-) definitive hematopoietic mesoderm and WNT-independent KDR(+)CD235a(+) primitive hematopoietic mesoderm revealed strong CDX gene expression within definitive hematopoietic mesoderm. Temporal expression analyses revealed that CDX4 was expressed exclusively within definitive hematopoietic KDR(+)CD235a(-) mesoderm in a WNT- and fibroblast growth factor-dependent manner (PMID:28408465)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cdx4	ENSMUSG00000031326
rattus_norvegicus	Cdx4	ENSRNOG00000002974

Paralogs (2): CDX1 (ENSG00000113722), CDX2 (ENSG00000165556)

Protein

Protein identifiers

Homeobox protein CDX-4 — O14627 (reviewed: O14627)

Alternative names: Caudal-type homeobox protein 4

All UniProt accessions (1): O14627

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Similarity. Belongs to the Caudal homeobox family.

RefSeq proteins (1): NP_005184* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000047	HTH_motif	Conserved_site
IPR001356	HD	Domain
IPR006820	Caudal_activation_dom	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR047152	Caudal_homeobox	Family

Pfam: PF00046, PF04731

UniProt features (7 total): region of interest 3, compositionally biased region 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14627-F1	63.87	0.23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 85 (showing top): ATF_B, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_AXIS_SPECIFICATION, PAX4_01, SHEPARD_CRASH_AND_BURN_MUTANT_UP, EFC_Q6, CREB_Q4, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_PLACENTA_DEVELOPMENT, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, ATF1_Q6, GOBP_EMBRYONIC_PATTERN_SPECIFICATION, SHIN_B_CELL_LYMPHOMA_CLUSTER_6

GO Biological Process (13): negative regulation of transcription by RNA polymerase II (GO:0000122), blood vessel development (GO:0001568), regulation of transcription by RNA polymerase II (GO:0006357), embryonic pattern specification (GO:0009880), anterior/posterior axis specification (GO:0009948), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944), digestive tract development (GO:0048565), labyrinthine layer development (GO:0060711), placenta development (GO:0001890), regulation of DNA-templated transcription (GO:0006355), multicellular organism development (GO:0007275), anterior/posterior pattern specification (GO:0009952)

GO Molecular Function (8): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
anatomical structure development	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
negative regulation of DNA-templated transcription	1
vasculature development	1
pattern specification process	1
embryo development	1
axis specification	1
anterior/posterior pattern specification	1
cellular developmental process	1
positive regulation of DNA-templated transcription	1
tube development	1
digestive system development	1
embryonic placenta development	1
animal organ development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
multicellular organismal process	1
regionalization	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription regulator activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

686 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDX4	TBPL2	Q6SJ96	906
CDX4	NAP1L2	Q9ULW6	865
CDX4	NAP1L1	P55209	762
CDX4	ISL1	P20663	579
CDX4	CHIC1	Q5VXU3	576
CDX4	SLC16A2	P36021	495
CDX4	FGF4	P08620	435
CDX4	TBX6	O95947	435
CDX4	LMO2	P25791	418
CDX4	PRR16	Q569H4	415
CDX4	SPATA22	Q8NHS9	405
CDX4	BTBD16	Q32M84	399
CDX4	MEIS1	O00470	399
CDX4	SLC7A3	Q8WY07	396
CDX4	LMX1A	Q8TE12	385

IntAct

28 interactions, top by confidence:

A	B	Type	Score
PRKAB2	CDX4	psi-mi:“MI:0915”(physical association)	0.740
CDX4	PRKAB2	psi-mi:“MI:0915”(physical association)	0.740
CDX4		psi-mi:“MI:0915”(physical association)	0.560
CDX4	LMO2	psi-mi:“MI:0915”(physical association)	0.560
CDX4	LMO1	psi-mi:“MI:0915”(physical association)	0.560
CDX4	CKS1B	psi-mi:“MI:0915”(physical association)	0.560
PRKAA1	CDX4	psi-mi:“MI:0915”(physical association)	0.560
	CDX4	psi-mi:“MI:0915”(physical association)	0.560
CKS1B	CDX4	psi-mi:“MI:0915”(physical association)	0.560
LMO1	CDX4	psi-mi:“MI:0915”(physical association)	0.560
BANP	CDX4	psi-mi:“MI:0915”(physical association)	0.560
CDX4	PRKAA2	psi-mi:“MI:0915”(physical association)	0.560
PITX1	CDX4	psi-mi:“MI:0915”(physical association)	0.370
PRKAA2	CDX4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): CKS1B (Two-hybrid), LMO1 (Two-hybrid), LMO2 (Two-hybrid), PRKAA1 (Two-hybrid), PRKAB2 (Two-hybrid), CDX4 (Two-hybrid), PRKAA2 (Two-hybrid), CDX4 (Affinity Capture-MS), CDX4 (Two-hybrid), CDX4 (Two-hybrid)

ESM2 similar proteins: A8XJD0, A8XSQ8, B3DM25, B7ZQA9, G5EDS1, G5EFY5, L8E946, O14627, O93366, P09013, P09014, P09089, P17486, P17488, P22809, P34766, P41936, P46692, P50574, P53772, P53773, P53774, P53775, Q01702, Q07424, Q18273, Q1KKX1, Q1KL12, Q1KL17, Q21305, Q22909, Q22910, Q26417, Q5J3Q5, Q6P2Z3, Q6P8A3, Q7T103, Q7ZYQ0, Q90270, Q90X89

Diamond homologs: A1YFA5, A2D5K9, A2D5Y4, A2T7F3, A2T7H5, A8XSQ8, O13074, O14627, O42504, P02830, P02832, P02833, P04476, P06798, P07548, P09013, P09014, P09017, P09019, P09021, P09023, P09024, P09067, P09070, P09071, P09077, P09079, P09080, P09085, P09092, P09629, P09630, P10038, P10178, P10284, P10629, P13545, P14838, P14839, P14840

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

39 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

383 predictions. Top by Δscore:

Variant	Effect	Δscore
X:73453512:AACAG:A	acceptor_gain	1.0000
X:73453515:AG:A	acceptor_gain	1.0000
X:73453516:GG:G	acceptor_gain	1.0000
X:73453516:GGGA:G	acceptor_gain	1.0000
X:73453671:G:GT	donor_gain	1.0000
X:73454373:TTTCA:T	acceptor_loss	1.0000
X:73454376:CAG:C	acceptor_loss	1.0000
X:73454377:A:AC	acceptor_loss	1.0000
X:73447752:ACGGG:A	donor_loss	0.9900
X:73447754:GG:G	donor_gain	0.9900
X:73447755:GG:G	donor_gain	0.9900
X:73447755:GGTG:G	donor_loss	0.9900
X:73447756:G:A	donor_loss	0.9900
X:73447756:G:GG	donor_gain	0.9900
X:73447757:T:A	donor_loss	0.9900
X:73453515:A:AG	acceptor_gain	0.9900
X:73453515:AGG:A	acceptor_gain	0.9900
X:73453516:G:GG	acceptor_gain	0.9900
X:73453516:GGG:G	acceptor_gain	0.9900
X:73453516:GGGAA:G	acceptor_gain	0.9900
X:73453585:G:GT	donor_gain	0.9900
X:73453660:CAG:C	donor_loss	0.9900
X:73453661:AG:A	donor_loss	0.9900
X:73453662:GGT:G	donor_loss	0.9900
X:73453663:G:GC	donor_loss	0.9900
X:73453671:GAA:G	donor_gain	0.9900
X:73453674:G:GG	donor_gain	0.9900
X:73453694:AT:A	donor_gain	0.9900
X:73454372:GTTTC:G	acceptor_loss	0.9900
X:73447751:GACGG:G	donor_gain	0.9800

AlphaMissense

1864 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:73453577:T:C	L188P	0.999
X:73453588:T:C	F192L	0.999
X:73453590:C:A	F192L	0.999
X:73453590:C:G	F192L	0.999
X:73454391:T:C	F221L	0.999
X:73454393:T:A	F221L	0.999
X:73454393:T:G	F221L	0.999
X:73454392:T:C	F221S	0.998
X:73454397:A:G	N223D	0.998
X:73454401:G:C	R224P	0.998
X:73453623:A:C	K203N	0.997
X:73453623:A:T	K203N	0.997
X:73453589:T:C	F192S	0.996
X:73454386:T:C	I219T	0.996
X:73454388:T:A	W220R	0.996
X:73454388:T:C	W220R	0.996
X:73454390:G:C	W220C	0.996
X:73454390:G:T	W220C	0.996
X:73454396:G:C	Q222H	0.996
X:73454396:G:T	Q222H	0.996
X:73454398:A:G	N223S	0.996
X:73454400:C:A	R224S	0.996
X:73454391:T:A	F221I	0.995
X:73454391:T:G	F221V	0.995
X:73454392:T:G	F221C	0.995
X:73454398:A:C	N223T	0.995
X:73454405:A:C	R225S	0.995
X:73454405:A:T	R225S	0.995
X:73454411:G:C	K227N	0.995
X:73454411:G:T	K227N	0.995

dbSNP variants (sampled 300 via entrez): RS1000275802 (X:73448488 C>A), RS1000349663 (X:73452156 G>A), RS1001048441 (X:73445873 G>T), RS1002110260 (X:73454111 G>A), RS1002742368 (X:73453329 C>T), RS1002884222 (X:73450815 A>G), RS1002948391 (X:73445648 T>C), RS1003308003 (X:73446072 A>G), RS1003533392 (X:73451197 T>C), RS1003698664 (X:73447816 T>C), RS1003845259 (X:73450922 G>A), RS1004131416 (X:73449035 G>T), RS1004895378 (X:73446389 C>A), RS1005799165 (X:73453399 T>C), RS1005851837 (X:73455349 T>C)

Disease associations

OMIM: gene MIM:300025 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects expression, decreases reaction, increases expression	2
bisphenol A	affects cotreatment, increases methylation	1
arsenite	increases methylation	1
sodium arsenite	decreases methylation, increases expression	1
CGP 52608	affects binding, increases reaction	1
belinostat	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects methylation	1
Carmustine	decreases expression	1
Catechin	affects cotreatment, decreases expression	1
Nickel	affects expression, decreases reaction	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.