CITED2

Chr 6

Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 2

Also known as: ASD8, MRG-1, MRG1, P35SRJ, VSD2

NCBI Gene: 10370ENSG00000164442UniProt: Q99967

The protein encoded by this gene inhibits transactivation of HIF1A-induced genes by competing with binding of hypoxia-inducible factor 1-alpha to p300-CH1. Mutations in this gene are a cause of cardiac septal defects. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

Primary Disease Associations & Inheritance

UniProtVentricular septal defect 2
UniProtAtrial septal defect 8
109
ClinVar variants
15
Pathogenic / LP
0.76
pLI score
0
Active trials
Clinical Summary— CITED2
🧬
Gene-Disease Validity (ClinGen)
congenital heart disease · ADModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.76) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 72 VUS of 109 total submissions
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?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.63LOEUF
pLI 0.763
Z-score 2.02
OE 0.00 (0.00–0.63)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.47Z-score
OE missense 1.10 (0.98–1.25)
179 obs / 162.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.63)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.10 (0.98–1.25)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.76
0≤1.21.6
LoF obs/exp: 0 / 4.8Missense obs/exp: 179 / 162.0Syn Z: -4.72

ClinVar Variant Classifications

109 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic1
VUS72
Likely Benign12
Benign9
Conflicting1
14
Pathogenic
1
Likely Pathogenic
72
VUS
12
Likely Benign
9
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
1
0
0
1
VUS
1
58
13
0
72
Likely Benign
0
3
3
6
12
Benign
0
0
5
4
9
Conflicting
—1
Total1623510109

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CITED2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Enhancer infestation drives tumorigenic activation of inactive B compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma.
Mizokami H et al.·EBioMedicine
2024
CITED2 affects leukemic cell survival by interfering with p53 activation.
Mattes K et al.·Cell Death Dis
2017
miR-18a-3p modulates the progression of polycystic ovary syndrome by targeting CITED2 and PI3K/AKT signaling pathway.
Yan S et al.·J Endocrinol Invest
2025
CITED2 is highly-expressed and PRX4 is poorly-expressed in preeclampsia and have diagnostic values.
Yang C et al.·J Hum Hypertens
2025
CITED2 and NCOR2 in anti-oestrogen resistance and progression of breast cancer.
van Agthoven T et al.·Br J Cancer
2009
Identification and Functional Verification of CITED2 Gene Promoter Region in Patients with Patent Ductus Arteriosus.
Chen Z et al.·Int J Mol Sci
2023Cohort
Minireview: transcriptional regulation of adrenocortical development.
Hammer GD et al.·Endocrinology
2005Review
Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development.
Weninger WJ et al.·Development
2005Functional
A gain-of-function mutation in CITED2 is associated with congenital heart disease.
Yadav ML et al.·Mutat Res
2021
CITED2 in breast carcinoma as a potent prognostic predictor associated with proliferation, migration and chemoresistance.
Minemura H et al.·Cancer Sci
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools