CITED2

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

Basic information

Region (hg38): 6:139371807-139374648

Links

ENSG00000164442 ∙ NCBI:10370 ∙ OMIM:602937 ∙ HGNC:1987 ∙ Uniprot:Q99967 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital heart defects, multiple types (Moderate), mode of inheritance: AD
• atrial septal defect 8 (Moderate), mode of inheritance: AD
• ventricular septal defect 2 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Atrial septal defect 8; Ventricular septal defect 2	AD	Cardiovascular	The conditions may involve congenital cardiac anomalies, and awareness may allow early diagnosis and interventions	Cardiovascular	16287139; 20654020; 22709740; 23082118
Variants may be involved in Premature ovarian failure (AD), but the evidence is unclear

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CITED2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CITED2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	4	10
missense		1	29	2		32
nonsense			1			1
start loss						0
frameshift						0
inframe indel			6	2		8
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	1	2	4
Total	0	1	37	11	6

Variants in CITED2

This is a list of pathogenic ClinVar variants found in the CITED2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-139373151-G-GGCT			Uncertain significance (Jan 31, 2017)
6-139373168-G-A		not specified	Likely benign (Jul 20, 2023)
6-139373191-C-A		Atrial septal defect 8	Uncertain significance (Mar 25, 2024)
6-139373244-T-G		Atrial septal defect 8	Likely pathogenic (Jul 15, 2018)
6-139373251-C-T			Uncertain significance (Oct 29, 2020)
6-139373259-A-G		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
6-139373260-TAAG-T			Uncertain significance (Oct 17, 2019)
6-139373274-T-C			Uncertain significance (Apr 08, 2021)
6-139373288-G-A			Benign (Aug 17, 2018)
6-139373318-G-A			Likely benign (Oct 23, 2017)
6-139373337-G-A		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
6-139373346-TTGCCGC-T		Atrial septal defect 8	Likely benign (Dec 31, 2019)
6-139373356-C-G		Inborn genetic diseases	Uncertain significance (Aug 15, 2023)
6-139373359-TGCCGCC-T		CITED2-related disorder	Benign (Mar 26, 2024)
6-139373363-G-A		CITED2-related disorder	Benign/Likely benign (Jun 01, 2024)
6-139373365-CGCCGCT-C		not specified • CITED2-related disorder	Benign (May 04, 2022)
6-139373371-T-C			Benign/Likely benign (Aug 01, 2024)
6-139373383-C-T		Inborn genetic diseases	Uncertain significance (Jan 11, 2023)
6-139373389-C-CGCCGCCCGAGCTGCTGCCAGAGCCGCCGGGGGTGCTGCT		CITED2-related disorder	Uncertain significance (Oct 24, 2022)
6-139373403-C-G			Likely benign (-)
6-139373408-AGAGCCGCCGGGGGTGCTGCTGCCGCCC-A		Ventricular septal defect 2	Pathogenic (Dec 01, 2005)
6-139373408-A-AGAGCCGCCGGGGGTGCTGCTGCCGCCC		CITED2-related disorder	Uncertain significance (Oct 20, 2023)
6-139373421-G-A		not specified	Uncertain significance (Sep 27, 2017)
6-139373435-C-G			Benign (Dec 31, 2019)
6-139373444-G-A			Likely benign (Feb 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CITED2	protein_coding	protein_coding	ENST00000367651	1	2365

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.763	0.229	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.474	179	162	1.10	0.00000745	1833
Missense in Polyphen		60	58.432	1.0268		717
Synonymous	-4.72	111	63.2	1.76	0.00000315	499
Loss of Function	2.02	0	4.76	0.00	2.13e-7	43

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional coactivator of the p300/CBP-mediated transcription complex. Acts as a bridge, linking TFAP2 transcription factors and the p300/CBP transcriptional coactivator complex in order to stimulate TFAP2-mediated transcriptional activation. Positively regulates TGF-beta signaling through its association with the SMAD/p300/CBP-mediated transcriptional coactivator complex. Stimulates the peroxisome proliferator- activated receptors PPARA transcriptional activity. Enhances estrogen-dependent transactivation mediated by estrogen receptors. Acts also as a transcriptional corepressor; interferes with the binding of the transcription factors HIF1A or STAT2 and the p300/CBP transcriptional coactivator complex. Participates in sex determination and early gonad development by stimulating transcription activation of SRY. Plays a role in controlling left- right patterning during embryogenesis; potentiates transcriptional activation of NODAL-mediated gene transcription in the left lateral plate mesoderm (LPM). Plays an essential role in differentiation of the adrenal cortex from the adrenogonadal primordium (AGP); stimulates WT1-mediated transcription activation thereby up-regulating the nuclear hormone receptor NR5A1 promoter activity. Associates with chromatin to the PITX2 P1 promoter region. {ECO:0000269|PubMed:11581164, ECO:0000269|PubMed:12586840, ECO:0000269|PubMed:15051727}.
• Disease: DISEASE: Ventricular septal defect 2 (VSD2) [MIM:614431]: A common form of congenital cardiovascular anomaly that may occur alone or in combination with other cardiac malformations. It can affect any portion of the ventricular septum, resulting in abnormal communications between the two lower chambers of the heart. Classification is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect. Large defects that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death. {ECO:0000269|PubMed:16287139}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Atrial septal defect 8 (ASD8) [MIM:614433]: A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria. {ECO:0000269|PubMed:16287139}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Mitophagy - animal - Homo sapiens (human);Gene expression (Transcription);mechanism of gene regulation by peroxisome proliferators via ppara;Generic Transcription Pathway;RNA Polymerase II Transcription;HIF-2-alpha transcription factor network;Activation of the TFAP2 (AP-2) family of transcription factors;TFAP2 (AP-2) family regulates transcription of other transcription factors;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors;HIF-1-alpha transcription factor network (Consensus)

Recessive Scores

• pRec: 0.372

Intolerance Scores

• rvis_EVS: -0.29
• rvis_percentile_EVS: 32.94

Haploinsufficiency Scores

• pHI: 0.744
• hipred: Y
• hipred_score: 0.713
• ghis: 0.635

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.924

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cited2
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; skeleton phenotype; renal/urinary system phenotype; embryo phenotype; respiratory system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; vision/eye phenotype; immune system phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;response to hypoxia;liver development;outflow tract morphogenesis;regulation of animal organ formation;regulation of transcription by RNA polymerase II;determination of left/right symmetry;heart development;sex determination;cell population proliferation;positive regulation of gene expression;negative regulation of gene expression;positive regulation of cell-cell adhesion;cell differentiation;negative regulation of cell migration;positive regulation of transforming growth factor beta receptor signaling pathway;response to fluid shear stress;positive regulation of peroxisome proliferator activated receptor signaling pathway;adrenal cortex formation;negative regulation of apoptotic process;response to estrogen;positive regulation of cell cycle;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;spleen development;ventricular septum morphogenesis;embryonic heart tube left/right pattern formation;negative regulation of transcription from RNA polymerase II promoter in response to hypoxia;left/right axis specification;nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry;positive regulation of male gonad development
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;protein-containing complex
• Molecular function: chromatin binding;DNA-binding transcription factor activity;transcription coactivator activity;transcription corepressor activity;protein binding;protein domain specific binding;histone acetyltransferase binding;LBD domain binding