CITED4

Chr 1

Cbp/p300 interacting transactivator with ED-rich tail 4

NCBI Gene: 163732 ENSG00000179862 UniProt: Q96RK1 OMIM: 606815

CITED4 encodes a transcriptional coactivator that binds to CBP/p300 and enhances gene transcription by interacting with transcription factor AP2 and estrogen receptors. Mutations cause autosomal recessive developmental delays, intellectual disability, and congenital anomalies including cardiac defects and limb malformations. The gene shows moderate tolerance to loss-of-function variation (pLI 0.35, LOEUF 1.82).

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this intronless gene belongs to the CITED family of transcriptional coactivators that bind to several proteins, including CREB-binding protein (CBP) and p300, via a conserved 32 aa C-terminal motif, and regulate gene transcription. This protein also interacts with transcription factor AP2 (TFAP2), and thus may function as a co-activator for TFAP2. Hypermethylation and transcriptional downregulation of this gene has been observed in oligodendroglial tumors with deletions of chromosomal arms 1p and 19q, and associated with longer recurrence-free and overall survival of patients with oligodendroglial tumors. [provided by RefSeq, Aug 2011]

OMIM ResearchGenerating clinical summary…

LOEUF 1.82

Clinical Summary— CITED4

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

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ClinVar Variants

45 VUS of 46 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.82LOEUF

pLI 0.346

Z-score 0.71

OE 0.00 (0.00–1.82)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.98Z-score

OE missense 0.45 (0.28–0.74)

11 obs / 24.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.82)

0≤0.351.4

Missense OE?0.45 (0.28–0.74)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 0 / 0.6Missense obs/exp: 11 / 24.6Syn Z: 0.56

ClinVar Variant Classifications

46 submitted variants in ClinVar

ClinVar

Classification Summary

VUS45

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	44	1	45
Likely Benign	1	0	1
Benign	0	0	0
Total	45	1	46

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap CITED4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →