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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CITED2
Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 2
Chromosome 6 · 6q24.1
NCBI Gene: 10370Ensembl: ENSG00000164442.11HGNC: HGNC:1987UniProt: A0A0A0MTM3
91PubMed Papers
22Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of cell migrationnucleoplasmresponse to fluid shear stresspositive regulation of peroxisome proliferator activated receptor signaling pathwayatrial septal defect 8ventricular septal defect 2Abnormality of the skeletal systematrial septal defect, sinus venosus type
✦AI Summary

CITED2 is a transcriptional coregulator that functions as a bridge between transcription factors and the p300/CBP coactivator complex 1. It acts as both a positive and negative regulator of gene expression: it enhances transcriptional activation by TFAP2 factors, TGF-β signaling, PPAR-α, and estrogen receptors, while simultaneously repressing HIF1A and STAT2-mediated transcription 1. CITED2 plays essential roles in cardiac and reproductive development—it regulates left-right patterning through NODAL-mediated transcription and controls adrenal cortex differentiation via WT1-mediated activation 2. In spermatogonial stem cells, CITED2 interacts with EP300 to promote proliferation and survival through HSPA6 regulation 3. Functionally, CITED2 mediates mechanical shear-induced suppression of matrix metalloproteinases in chondrocytes via TGF-β signaling 4 and exerts anti-inflammatory effects in lung fibroblasts by inhibiting the NF-κB pathway 5. Clinically, CITED2 mutations are associated with congenital heart defects; promoter variants reduce CITED2 expression and correlate with ventricular septal defects 6 and atrial septal defects 7. These findings establish CITED2 as a critical developmental regulator with implications for cardiac malformation pathogenesis.

Sources cited
1
CITED2 encodes p35srj, a nuclear protein binding p300/CBP; interferes with HIF-1α recruitment of p300/CBP; gene structure and chromosome localization
PMID: 10552932
2
CITED2 is a key regulator of placental development and acts as a coregulator modulating transcription factor activities
PMID: 38922923
3
CITED2 binding to EP300 regulates human spermatogonial stem cell proliferation and survival through HSPA6
PMID: 40313859
4
CITED2 mediates shear-induced down-regulation of MMP-1 and MMP-13 via TGF-β-dependent pathway in chondrocytes
PMID: 12960175
5
CITED2 alleviates lipopolysaccharide-induced inflammation and pyroptosis in lung fibroblasts by inhibiting NF-κB pathway
PMID: 35789404
6
CITED2 promoter variants in patent ductus arteriosus patients affect transcriptional activity and CITED2 protein expression
PMID: 38003393
7
CITED2 promoter variants in atrial septal defect patients alter transcriptional activity and are involved in ASD pathogenesis
PMID: 36286273
Disease Associationsⓘ22
atrial septal defect 8Open Targets
0.62Moderate
ventricular septal defect 2Open Targets
0.53Moderate
Abnormality of the skeletal systemOpen Targets
0.47Moderate
atrial septal defect, sinus venosus typeOpen Targets
0.38Weak
atrial septal defect, ostium secundum typeOpen Targets
0.37Weak
type 2 diabetes mellitusOpen Targets
0.29Weak
smoking initiationOpen Targets
0.25Weak
diabetes mellitusOpen Targets
0.24Weak
congenital heart diseaseOpen Targets
0.24Weak
alcohol drinkingOpen Targets
0.24Weak
metabolic syndromeOpen Targets
0.24Weak
non-alcoholic fatty liver diseaseOpen Targets
0.20Weak
Disorder of lipid metabolismOpen Targets
0.20Weak
Abruptio PlacentaeOpen Targets
0.20Weak
prostate carcinomaOpen Targets
0.19Weak
diabetic neuropathyOpen Targets
0.19Weak
physical activityOpen Targets
0.19Weak
cardiovascular diseaseOpen Targets
0.19Weak
hypertensionOpen Targets
0.19Weak
genetic disorderOpen Targets
0.19Weak
Atrial septal defect 8UniProt
Ventricular septal defect 2UniProt
Pathogenic Variants1
NM_006079.5(CITED2):c.701A>C (p.Glu234Ala)Likely pathogenic
Atrial septal defect 8
★☆☆☆2018→ Residue 234
View on ClinVar ↗
Related Genes
HIF1AProtein interaction100%TP53Protein interaction100%CREBBPProtein interaction100%EP300Protein interaction100%EPAS1Protein interaction100%FOXO3Protein interaction100%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
68%
Lung
59%
Liver
43%
Heart
28%
Brain
12%
Gene Interaction Network
Click a node to explore
CITED2HIF1ATP53CREBBPEP300EPAS1FOXO3
PROTEIN STRUCTURE
Preparing viewer…
PDB7QGS · 2.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.59Moderately Constrained
pLIⓘ
0.90Intermediate
Observed/Expected LoF0.19 [0.07–0.59]
RankingsWhere CITED2 stands among ~20K protein-coding genes
  • #5,237of 20,598
    Most Researched91
  • #4,916of 5,498
    Most Pathogenic Variants1
  • #3,976of 17,882
    Most Constrained (LOEUF)0.59 · top quartile
Genes detectedCITED2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Human Genetics of Ventricular Septal Defect.
PMID: 38884729
Adv Exp Med Biol · 2024
1.00
2
CRISPR/Cas9-mediated gene disruption determines the roles of MITF and CITED2 in human mast cell differentiation.
PMID: 38838231
Blood Adv · 2024
0.90
3
Identification and Functional Verification of CITED2 Gene Promoter Region in Patients with Patent Ductus Arteriosus.
PMID: 38003393
Int J Mol Sci · 2023
0.80
4
Genetic Variants of
PMID: 36286273
J Cardiovasc Dev Dis · 2022
0.70
5
Cited2 is a key regulator of placental development and plasticity.
PMID: 38922923
Bioessays · 2024
0.60