WRAP53

Chr 17AR

WD repeat containing antisense to TP53

Also known as: DKCB3, TCAB1, WDR79

NCBI Gene: 55135ENSG00000141499UniProt: Q9BUR4

This gene encodes an essential component of the telomerase holoenzyme complex, a ribonucleoprotein complex required for telomere synthesis. This protein is enriched in Cajal bodies, nuclear sites of RNP processing that are important for telomerase function. It interacts with dyskerin, TERT and TERC, other components of active telomerase, and with small Cajal body RNAs (scaRNAs), which are involved in modifying splicing RNAs. This mRNA also functions as a p53 antisense transcript, that regulates endogenous p53 mRNA levels and further induction of p53 protein by targeting the 5' untranslated region of p53 mRNA. Alternatively spliced transcript variants which differ only in the 5' UTR have been found for this gene. [provided by RefSeq, Mar 2011]

Primary Disease Associations & Inheritance

Dyskeratosis congenita, autosomal recessive 3MIM #613988
AR
655
ClinVar variants
52
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— WRAP53
🧬
Gene-Disease Validity (ClinGen)
dyskeratosis congenita · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 Pathogenic / Likely Pathogenic· 326 VUS of 655 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.69LOEUF
pLI 0.000
Z-score 2.82
OE 0.43 (0.27–0.69)
Tolerant

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.
0.02Z-score
OE missense 1.00 (0.91–1.09)
315 obs / 316.0 exp
Tolerant

Mild missense constraint

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.0.43 (0.27–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.91–1.09)
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.1.01
0≤1.21.6
LoF obs/exp: 12 / 28.2Missense obs/exp: 315 / 316.0Syn Z: -0.08

ClinVar Variant Classifications

655 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic7
VUS326
Likely Benign233
Benign20
Conflicting24
45
Pathogenic
7
Likely Pathogenic
326
VUS
233
Likely Benign
20
Benign
24
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
42
0
45
Likely Pathogenic
2
2
3
0
7
VUS
27
241
57
1
326
Likely Benign
0
6
89
138
233
Benign
0
3
16
1
20
Conflicting
—24
Total30254207140655

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

View in ClinVar →

Protein Context — Lollipop Plot

WRAP53 · protein map & ClinVar variants

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

Gene2Phenotype Curations

WRAP53-related dyskeratosis congenita

strong
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersCancer
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Dyskeratosis congenita, autosomal recessive 3

MIM #613988

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — WRAP53
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Overexpression of WRAP53 is associated with development and progression of esophageal squamous cell carcinoma.
Rao X et al.·PLoS One
2014
Clinical, cellular, and bioinformatic analyses reveal involvement of WRAP53 overexpression in carcinogenesis of lung adenocarcinoma.
Yuan XS et al.·Tumour Biol
2017
A unique homozygous WRAP53 Arg298Trp mutation underlies dyskeratosis congenita in a Chinese Han family.
Shao Y et al.·BMC Med Genet
2018Case report
WRAP53 is an independent prognostic factor in rectal cancer- a study of Swedish clinical trial of preoperative radiotherapy in rectal cancer patients.
Zhang H et al.·BMC Cancer
2012Clinical trial
Next-generation sequencing errors due to genetic variation in WRAP53 encoding TCAB1 on chromosome 17.
Savage SA et al.·Hum Mutat
2022
The Sub-Cellular Localization of WRAP53 Has Prognostic Impact in Breast Cancer.
Silwal-Pandit L et al.·PLoS One
2015
Investigation of long noncoding RNAs expression profile as potential serum biomarkers in patients with hepatocellular carcinoma.
Kamel MM et al.·Transl Res
2016Cohort
WRAP53 is Downregulated in Acute Myeloid Leukemia Patients and Positively Correlates With HTERT Expression.
Gadelha RB et al.·Cancer Rep (Hoboken)
2026Cohort
The p53 tumor suppressor: a master regulator of diverse cellular processes and therapeutic target in cancer.
Farnebo M et al.·Biochem Biophys Res Commun
2010Review
A protein microarray-based serum proteomic investigation reveals distinct autoantibody signature in colorectal cancer.
Barpanda A et al.·Proteomics Clin Appl
2023
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