WRAP53

Summary

WRAP53 (WD repeat containing antisense to TP53, HGNC:25522) is a protein-coding gene on chromosome 17p13.1, encoding Telomerase Cajal body protein 1 (Q9BUR4). RNA chaperone that plays a key role in telomere maintenance and RNA localization to Cajal bodies.

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.

Source: NCBI Gene 55135 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dyskeratosis congenita, autosomal recessive 3 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 571 total — 4 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 67
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001143992

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25522
Approved symbol	WRAP53
Name	WD repeat containing antisense to TP53
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10385, TCAB1
Ensembl gene	ENSG00000141499
Ensembl biotype	protein_coding
OMIM	612661
Entrez	55135

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 14 protein_coding, 5 nonsense_mediated_decay, 3 retained_intron

ENST00000316024, ENST00000396463, ENST00000431639, ENST00000457584, ENST00000463804, ENST00000467699, ENST00000471973, ENST00000498114, ENST00000498311, ENST00000534050, ENST00000698742, ENST00000698743, ENST00000698744, ENST00000698745, ENST00000698746, ENST00000698747, ENST00000868853, ENST00000868854, ENST00000932533, ENST00000932534, ENST00000932535, ENST00000964568

RefSeq mRNA: 4 — MANE Select: NM_001143992 NM_001143990, NM_001143991, NM_001143992, NM_018081

CCDS: CCDS11119

Canonical transcript exons

ENST00000396463 — 11 exons

Exon	Start	End
ENSE00000949236	7701459	7701549
ENSE00003545156	7689224	7689322
ENSE00003573548	7702993	7703127
ENSE00003600532	7700741	7700829
ENSE00003613545	7689590	7689701
ENSE00003625326	7688648	7689079
ENSE00003640787	7702344	7702552
ENSE00003672619	7701657	7701789
ENSE00003682790	7702743	7702846
ENSE00003899949	7703243	7703502
ENSE00003974617	7688477	7688561

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 90.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.3752 / max 67.6267, expressed in 1766 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159328	7.2274	1614
159327	1.9279	948
159324	1.6206	769
159326	0.3641	132
159325	0.2353	107

Top tissues by expression

278 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	90.23	gold quality
epithelium of bronchus	UBERON:0002031	87.10	gold quality
bronchus	UBERON:0002185	86.80	gold quality
bronchial epithelial cell	CL:0002328	86.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.56	gold quality
pancreatic ductal cell	CL:0002079	86.09	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.64	gold quality
ganglionic eminence	UBERON:0004023	85.01	gold quality
granulocyte	CL:0000094	84.84	gold quality
tibialis anterior	UBERON:0001385	84.06	gold quality
embryo	UBERON:0000922	83.84	gold quality
cortical plate	UBERON:0005343	83.19	gold quality
mucosa of transverse colon	UBERON:0004991	82.70	gold quality
ventricular zone	UBERON:0003053	82.35	gold quality
lower esophagus mucosa	UBERON:0035834	81.45	gold quality
tendon of biceps brachii	UBERON:0008188	80.91	gold quality
apex of heart	UBERON:0002098	80.88	gold quality
ileal mucosa	UBERON:0000331	80.64	gold quality
nasal cavity mucosa	UBERON:0001826	79.69	gold quality
spleen	UBERON:0002106	79.62	gold quality
oocyte	CL:0000023	79.38	gold quality
deltoid	UBERON:0001476	78.96	silver quality
gastrocnemius	UBERON:0001388	78.71	gold quality
blood	UBERON:0000178	78.64	gold quality
nasal cavity epithelium	UBERON:0005384	78.49	gold quality
lymph node	UBERON:0000029	78.30	gold quality
vena cava	UBERON:0004087	78.25	gold quality
cerebellar hemisphere	UBERON:0002245	78.19	gold quality
muscle of leg	UBERON:0001383	78.14	gold quality
gluteal muscle	UBERON:0002000	78.09	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.82

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, TP53

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Common variation in TP53 or WDR79 could be associated with ER negative breast cancers. (PMID:17683073)
• identification of telomerase holoenzyme subunit, TCAB1, enriched in Cajal bodies; it associates with active telomerase, telomerase components & small Cajal body RNAs; TCAB1 controls telomerase trafficking & required for telomere synthesis in cancer cells (PMID:19179534)
• We have identified a natural antisense transcript of p53, designated Wrap53, that regulates endogenous p53 mRNA levels and further induction of p53 protein by targeting the 5’ untranslated region of p53 mRNA. (PMID:19250907)
• Studies show that a linked, positively selected allele at the nearby gene WDR79 may be partly responsible for the sequence diversity profile of TP53. (PMID:19797907)
• WRAP53 mediates the interaction between SMN and associated proteins, which is important for nuclear targeting of SMN and the subsequent localization of the SMN complex to Cajal bodies (PMID:21072240)
• Compound heterozygous mutations in TCAB1 disrupt telomerase localization to Cajal bodies, resulting in misdirection of telomerase RNA to nucleoli, which prevents telomerase from elongating telomeres (PMID:21205863)
• Knockdown of the WRAP53 protein triggers massive apoptosis through the mitochondrial pathway. (PMID:21368886)
• although Cajal bodies are important for recruitment of telomerase, TCAB1 has an additional role in this process that is independent of these structures (PMID:22547674)
• Examined expression of WRAP53 protein in rectal cancers and analyzed its relationship to the response to preoperative radiotherapy and patient survival.In radiotherapy group, positive WRAP53 in the metastasis correlated with better survival. (PMID:22805008)
• SNPs in WRAP53 (rs2287497 and rs2287498) have stronger association with an ovarian cancer risk than rs1042522 in TP53. (PMID:23192612)
• Intronic mutation outside overlapping regions of p53/wrap53 genes are associated with breast cancer. (PMID:23886136)
• WRAP53 is associated with development and progression of esophageal squamous cell carcinoma (PMID:24626331)
• The data indicated that TCAB1 might facilitate the occurrence and development of head and neck carcinomas. (PMID:25070141)
• Studied the association of a frequent genetic variation in WRAP53, rs2287499 (C/G), with breast cancer risk and prognosis among Iranian-Azeri population. (PMID:25134915)
• nuclear expression of WRAP53beta promotes tumor cell death in response to radiotherapy and is a promising predictor of radiotherapy response in patients with HNSCC (PMID:25456005)
• Study finds that TRiC is required for folding the telomerase cofactor TCAB1, which controls trafficking of telomerase and small Cajal body RNAs (scaRNAs). (PMID:25467444)
• WRAP53beta as a novel regulator of DSB repair by providing a scaffold for DNA repair factors. (PMID:25512560)
• Decreasing the expression of WRAP53 using RNA interference technique can enhance the radiosensitivity. (PMID:25854392)
• The telomerase holoenzyme Cajal body-associated protein, TCAB1, was released from telomerase RNA in mitotic cells coincident with TCAB1 delocalization from Cajal bodies. (PMID:26170453)
• Moreover, our current observations identify the nuclear levels of WRAP53beta as a promising biomarker for the survival of patients with ovarian cancer. (PMID:26426684)
• the sub-cellular localization of the WRAP53 protein has a significant impact on breast cancer survival. (PMID:26460974)
• This study showed that UCA1 and WRAP53 upregulation may serve as novel serum biomarkers for hepatocellular carcinoma diagnosis and prognosis. (PMID:26551349)
• The interaction of MDC1 with RNF8, but not with ATM requires WRAP53beta, suggesting that WRAP53beta facilitates the former interaction without altering phosphorylation of MDC1 by ATM. (PMID:26734725)
• The present findings indicate that WRAP53beta and RNF8 are rate-limiting factors in the repair of DNA double-strand breaks and raise the possibility that upregulation of WRAP53beta may contribute to genomic stability in and survival of cancer cells. (PMID:27310875)
• we analyzed the association between the WRAP53 gene rs2287499 C>G polymorphism and risk of cancer using five case-control studies.In the overall analysis, no significant association between rs2287499 and risk of cancer was found. (PMID:27525856)
• in response to DNA damage the Cajal body protein WRAP53beta is phosphorylated by ATM and that this phosphorylation is important for the recruitment of WRAP53beta to DNA lesions, its interaction with gammaH2AX, subsequent localization of the downstream repair factor 53BP1 to DNA breaks, as well as for HR and NHEJ repair. (PMID:27715493)
• The depletion of WRAP53 inhibits the proliferation of lung-adenocarcinoma A549 and SPC-A-1 cells via G1/S cell-cycle arrest. Several proteins interacting with WRAP53 were identified through co-immunoprecipitation and liquid chromatography/mass spectrometry. (PMID:28347242)
• WDR79 colocalized and interacted with USP7 in the nucleus of non-small cell lung cancer cells. This event, in turn, reduced the ubiquitination of Mdm2 and p53, thereby increasing the stability and extending the half-life of the two proteins. (PMID:28406480)
• The results collectively suggest that WDR79 and SMN play evolutionarily conserved cooperative functions in the nervous system and suggest that WDR79/TCAB1 may have the potential to modify SMA pathogenesis. (PMID:28502804)
• Data show that up-regulated expression of telomerase Cajal body protein 1 (TCAB1), induced by Epstein-Barr virus (EBV) in the development of nasopharyngeal carcinoma (NPC), is involved in stimulating telomerase activity and regulating the DNA damage response. (PMID:28607398)
• a unique homozygous WRAP53 mutation site underlies the development of dyskeratosis congenita in a Chinese Han family (PMID:29514627)
• These findings reveal that WDR79 is a novel UHRF1 regulator by maintaining UHRF1 stability. (PMID:29516630)
• Wrap53 is likely a potential oncogene or possesses oncogenic activity in colorectal cancer, promoting colorectal tumorigenesis. (PMID:30175821)
• we suggest that TDP-43 and WDR79 have separate roles in determining Cajal bodies (CBs) localization of subsets of C/D and H/ACA scaRNAs. (PMID:30759234)
• analyze a haplotype comprising four SNPs, including rs1042522, rs17878362, rs2287499, and rs2287498, which are located at 5’ regions of the TP53 and WRAP53 genes as molecular prognostic and predictive biomarkers for breast cancer. (PMID:31387111)
• Biallelic mutations in WRAP53 result in dysfunctional telomeres, Cajal bodies and DNA repair, thereby causing Hoyeraal-Hreidarsson syndrome. (PMID:32303682)
• Nuclear WRAP53 promotes neuronal survival and functional recovery after stroke. (PMID:33028529)
• [Effect of WRAP53 beta Targeted Co-Inhibitory Pathways Based on Comprehensive Bioinformatics Analysis in Treating Squamous Cell Carcinoma of the Head and Neck]. (PMID:35642155)
• Next-generation sequencing errors due to genetic variation in WRAP53 encoding TCAB1 on chromosome 17. (PMID:36116037)
• Differential effects of WRAP53 transcript variants on non-small cell lung cancer cell behaviors. (PMID:36706151)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wrap53	ENSDARG00000086150
mus_musculus	Wrap53	ENSMUSG00000041346
rattus_norvegicus	Efnb3	ENSRNOG00000010320
drosophila_melanogaster	WDR79	FBGN0031782
caenorhabditis_elegans	tcab-1	WBGENE00013669

Protein

Protein identifiers

Telomerase Cajal body protein 1 — Q9BUR4 (reviewed: Q9BUR4)

Alternative names: WD repeat-containing protein 79, WD40 repeat-containing protein antisense to TP53 gene

All UniProt accessions (10): A0A8V8TM44, A0A8V8TM47, A0A8V8TM74, A0A8V8TMM9, A0A8V8TNM2, A0A8V8TNY4, E9PMG4, E9PMR3, Q9BUR4, K7EJ50

UniProt curated annotations — full annotation on UniProt →

Function. RNA chaperone that plays a key role in telomere maintenance and RNA localization to Cajal bodies. Specifically recognizes and binds the Cajal body box (CAB box) present in both small Cajal body RNAs (scaRNAs) and telomerase RNA template component (TERC). Essential component of the telomerase holoenzyme complex, a ribonucleoprotein complex essential for the replication of chromosome termini that elongates telomeres in most eukaryotes. In the telomerase holoenzyme complex, required to stimulate the catalytic activity of the complex. Acts by specifically binding the CAB box of the TERC RNA and controlling the folding of the CR4/CR5 region of the TERC RNA, a critical step for telomerase activity. In addition, also controls telomerase holoenzyme complex localization to Cajal body. During S phase, required for delivery of TERC to telomeres during S phase and for telomerase activity. In addition to its role in telomere maintenance, also required for Cajal body formation, probably by mediating localization of scaRNAs to Cajal bodies. Also plays a role in DNA repair: phosphorylated by ATM in response to DNA damage and relocalizes to sites of DNA double-strand breaks to promote the repair of DNA double-strand breaks. Acts by recruiting the ubiquitin ligase RNF8 to DNA breaks and promote both homologous recombination (HR) and non-homologous end joining (NHEJ).

Subunit / interactions. Component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1. Interacts with the chaperonin-containing T-complex (TRiC) complex; which mediates the folding of WRAP53/TCAB1. Interacts with COIL. Interacts with SMN1. Interacts with RNF8. Interacts with histone H2AX.

Subcellular location. Nucleus. Cajal body. Chromosome. Telomere.

Tissue specificity. Expressed in all tissues and cell lines examined.

Post-translational modifications. Phosphorylated at Ser-64 by ATM in response to DNA damage, promoting its interaction with histone H2AX and localization to sites of DNA double-strand breaks.

Disease relevance. Dyskeratosis congenita, autosomal recessive, 3 (DKCB3) [MIM:613988] A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. The disease is caused by variants affecting the gene represented in this entry.

Induction. (Microbial infection) Over-expressed following infection by Epstein-Barr virus.

Miscellaneous. The mRNA encoding this protein plays a critical role in the regulation of p53/TP53 expression at the post-transcriptional level; it is involved both in maintaining basal p53/TP53 mRNA levels and in p53/TP53 induction upon DNA damage.

Similarity. Belongs to the TCAB1 family.

RefSeq proteins (4): NP_001137462, NP_001137463, NP_001137464, NP_060551 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR051150	SWT21/TCAB1_mRNA_Telomere	Family

Pfam: PF00400

UniProt features (75 total): strand 36, modified residue 10, sequence variant 10, repeat 6, sequence conflict 3, compositionally biased region 2, helix 2, turn 2, region of interest 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8OUE	ELECTRON MICROSCOPY	2.7
9QB2	ELECTRON MICROSCOPY	3
8OUF	ELECTRON MICROSCOPY	3.1
7TRC	ELECTRON MICROSCOPY	3.3
7BGB	ELECTRON MICROSCOPY	3.4
9QB3	ELECTRON MICROSCOPY	3.9
7V9A	ELECTRON MICROSCOPY	3.94

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BUR4-F1	73.96	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (10): 26, 30, 54, 64, 85, 90, 112, 114, 489, 491

Mutagenesis-validated functional residues (1):

Position	Phenotype
64	abolished phosphorylation by atm and impaired ability to promote dna repair.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-171319	Telomere Extension By Telomerase
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis
R-HSA-157579	Telomere Maintenance
R-HSA-1640170	Cell Cycle
R-HSA-180786	Extension of Telomeres
R-HSA-390466	Chaperonin-mediated protein folding
R-HSA-391251	Protein folding
R-HSA-392499	Metabolism of proteins
R-HSA-73886	Chromosome Maintenance

MSigDB gene sets: 372 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, CREL_01, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_REGULATION_OF_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION

GO Biological Process (15): DNA repair (GO:0006281), telomere maintenance via telomerase (GO:0007004), Cajal body organization (GO:0030576), telomere formation via telomerase (GO:0032203), positive regulation of telomere maintenance via telomerase (GO:0032212), RNA folding (GO:0034337), positive regulation of DNA repair (GO:0045739), scaRNA localization to Cajal body (GO:0090666), telomerase RNA localization to Cajal body (GO:0090671), positive regulation of establishment of protein localization to telomere (GO:1904851), protein localization to Cajal body (GO:1904867), positive regulation of double-strand break repair via homologous recombination (GO:1905168), positive regulation of double-strand break repair (GO:2000781), positive regulation of double-strand break repair via nonhomologous end joining (GO:2001034), DNA damage response (GO:0006974)

GO Molecular Function (10): RNA binding (GO:0003723), ubiquitin protein ligase binding (GO:0031625), histone binding (GO:0042393), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), protein-folding chaperone binding (GO:0051087), telomerase RNA binding (GO:0070034), protein carrier activity (GO:0140597), RNA folding chaperone (GO:0140691), protein binding (GO:0005515)

GO Cellular Component (9): chromosome, telomeric region (GO:0000781), nucleoplasm (GO:0005654), telomerase holoenzyme complex (GO:0005697), cytosol (GO:0005829), Cajal body (GO:0015030), nuclear body (GO:0016604), site of double-strand break (GO:0035861), nucleus (GO:0005634), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Extension of Telomeres	1
Chaperonin-mediated protein folding	1
Chromosome Maintenance	1
Telomere Maintenance	1
Protein folding	1
Metabolism of proteins	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
telomerase activity	2
telomere-telomerase complex assembly	2
RNA localization to Cajal body	2
positive regulation of double-strand break repair	2
binding	2
cellular anatomical structure	2
intracellular membraneless organelle	2
DNA metabolic process	1
DNA damage response	1
RNA-templated DNA biosynthetic process	1
telomere maintenance via telomere lengthening	1
nuclear body organization	1
telomere assembly	1
telomere maintenance via telomerase	1
regulation of telomere maintenance via telomerase	1
positive regulation of telomere maintenance via telomere lengthening	1
positive regulation of DNA biosynthetic process	1
cellular process	1
DNA repair	1
regulation of DNA repair	1
positive regulation of response to stimulus	1
positive regulation of DNA metabolic process	1
telomerase RNA localization	1
establishment of protein localization to telomere	1
regulation of establishment of protein localization to telomere	1
positive regulation of establishment of protein localization	1
protein localization to nuclear body	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
positive regulation of DNA recombination	1
double-strand break repair	1
positive regulation of DNA repair	1
regulation of double-strand break repair	1
double-strand break repair via nonhomologous end joining	1
regulation of double-strand break repair via nonhomologous end joining	1
cellular response to stress	1
nucleic acid binding	1
ubiquitin-like protein ligase binding	1
RNA binding	1

Protein interactions and networks

STRING

1064 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WRAP53	DKC1	O60832	999
WRAP53	NHP2	Q9NX24	998
WRAP53	NOP10	Q9NPE3	998
WRAP53	TERT	O14746	996
WRAP53	CTC1	Q2NKJ3	871
WRAP53	RUVBL2	Q9Y230	814
WRAP53	SHQ1	Q6PI26	812
WRAP53	TINF2	Q9BSI4	810
WRAP53	RTEL1	Q9NZ71	809
WRAP53	CTCF	P49711	807
WRAP53	GAR1	Q9NY12	778
WRAP53	RUVBL1	P82276	769
WRAP53	COIL	P38432	768
WRAP53	PARN	O95453	703
WRAP53	FBL	P22087	651

IntAct

87 interactions, top by confidence:

A	B	Type	Score
DKC1	NAF1	psi-mi:“MI:0914”(association)	0.900
NOP10	DKC1	psi-mi:“MI:0914”(association)	0.890
WRAP53	DKC1	psi-mi:“MI:0914”(association)	0.830
DKC1	TERT	psi-mi:“MI:0915”(physical association)	0.750
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
WRAP53	TCP1	psi-mi:“MI:0914”(association)	0.690
WRAP53	CCT6A	psi-mi:“MI:0914”(association)	0.640
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
WRAP53		psi-mi:“MI:0914”(association)	0.620
WRAP53		psi-mi:“MI:0915”(physical association)	0.620
WRAP53	COIL	psi-mi:“MI:0915”(physical association)	0.560
WRAP53	SMN1	psi-mi:“MI:0915”(physical association)	0.560
WRAP53	COIL	psi-mi:“MI:0914”(association)	0.560
VAC14	WRAP53	psi-mi:“MI:0915”(physical association)	0.560
UBAP2	WRAP53	psi-mi:“MI:0915”(physical association)	0.560
GAR1	PRMT5	psi-mi:“MI:0914”(association)	0.530
FAM43A	FTL	psi-mi:“MI:0914”(association)	0.530
CCT7	PEX7	psi-mi:“MI:0914”(association)	0.530
CCT6	WRAP53	psi-mi:“MI:0915”(physical association)	0.500
KPNB1	SMN1	psi-mi:“MI:0914”(association)	0.500
WRAP53	WRAP53	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (152): WRAP53 (Affinity Capture-MS), WRAP53 (Affinity Capture-MS), MDC1 (Affinity Capture-Western), RNF8 (Affinity Capture-Western), WRAP53 (Affinity Capture-Western), H2AFX (Affinity Capture-Western), HNRNPU (Co-fractionation), ZFHX3 (Affinity Capture-MS), CCT6A (Affinity Capture-MS), DKC1 (Affinity Capture-MS), MYBPH (Affinity Capture-MS), NDUFV3 (Affinity Capture-MS), TCP1 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), STK24 (Affinity Capture-MS)

ESM2 similar proteins: A1A4I4, A5PKD8, A6NED2, A8MQ27, O35465, O60294, O75808, O94819, O95382, P70268, Q0MW30, Q14318, Q16512, Q2T9J0, Q32NY4, Q32P44, Q3B7U9, Q3MHW0, Q3U5Q7, Q3USL1, Q4R828, Q561R2, Q5EBM0, Q5EBP3, Q5PQP9, Q60806, Q63433, Q6PAT0, Q7T0L4, Q8BNW9, Q8BTU7, Q8BYR1, Q8IYL2, Q8N5A5, Q8NEP7, Q8VC03, Q8VHS5, Q8WXI3, Q91ZT7, Q96C12

Diamond homologs: O59762, Q3SWZ7, Q5U2W5, Q5XII5, Q60525, Q6NL34, Q8VC51, Q9BUR4, B2ZZS9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATM	“up-regulates activity”	WRAP53	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of tubulin folding intermediates by CCT/TriC	7	51.0×	7e-09
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	7	49.2×	7e-09
Chaperonin-mediated protein folding	8	41.5×	5e-09
Prefoldin mediated transfer of substrate to CCT/TriC	6	40.7×	4e-07
Protein folding	8	35.8×	7e-09
Association of TriC/CCT with target proteins during biosynthesis	6	30.3×	2e-06
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	5	25.9×	6e-05
Cargo trafficking to the periciliary membrane	5	21.4×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	7	66.6×	2e-09
binding of sperm to zona pellucida	5	27.4×	1e-04
protein folding	6	8.1×	4e-03
protein stabilization	7	6.1×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

571 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	4
Uncertain significance	280
Likely benign	218
Benign	20

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1526566	GRCh37/hg19 17p13.1(chr17:7020054-8086290)	Pathogenic
2664373	NM_001143992.2(WRAP53):c.904G>T (p.Val302Phe)	Pathogenic
30976	NM_001143992.2(WRAP53):c.1126C>T (p.His376Tyr)	Pathogenic
638511	NM_001143992.2(WRAP53):c.1118del (p.Leu373fs)	Pathogenic
1713233	NC_000017.10:g.7584834_7594887del	Likely pathogenic
41252	NM_001143992.2(WRAP53):c.492C>A (p.Phe164Leu)	Likely pathogenic
423002	NM_001143992.2(WRAP53):c.1366_1367del (p.Ser456fs)	Likely pathogenic
988280	NM_001143992.2(WRAP53):c.847C>T (p.Leu283Phe)	Likely pathogenic

SpliceAI

1879 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7689075:GACAC:G	donor_gain	1.0000
17:7689080:G:GG	donor_gain	1.0000
17:7700735:GTATA:G	acceptor_loss	1.0000
17:7700736:TATA:T	acceptor_loss	1.0000
17:7700738:TAG:T	acceptor_loss	1.0000
17:7700739:A:C	acceptor_loss	1.0000
17:7700828:TA:T	donor_gain	1.0000
17:7700829:AG:A	donor_loss	1.0000
17:7700830:G:GG	donor_gain	1.0000
17:7700831:T:G	donor_loss	1.0000
17:7701458:GC:G	acceptor_gain	1.0000
17:7701651:CCCCA:C	acceptor_loss	1.0000
17:7701652:CCCAG:C	acceptor_loss	1.0000
17:7701653:CCA:C	acceptor_loss	1.0000
17:7701655:A:AG	acceptor_gain	1.0000
17:7701655:AG:A	acceptor_gain	1.0000
17:7701656:G:GC	acceptor_gain	1.0000
17:7701656:GG:G	acceptor_gain	1.0000
17:7701656:GGA:G	acceptor_gain	1.0000
17:7701656:GGAT:G	acceptor_gain	1.0000
17:7701785:ATTTG:A	donor_gain	1.0000
17:7701786:TTTG:T	donor_gain	1.0000
17:7701787:TTG:T	donor_gain	1.0000
17:7701788:TGGT:T	donor_loss	1.0000
17:7701790:G:GG	donor_gain	1.0000
17:7701790:GTAA:G	donor_loss	1.0000
17:7701791:TAAG:T	donor_loss	1.0000
17:7702342:A:AG	acceptor_gain	1.0000
17:7702343:G:GG	acceptor_gain	1.0000
17:7702550:AAGGT:A	donor_loss	1.0000

AlphaMissense

3563 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7689321:T:A	W177R	0.999
17:7689321:T:C	W177R	0.999
17:7689640:G:C	R194P	0.999
17:7701466:A:C	S247R	0.998
17:7701468:C:A	S247R	0.998
17:7701468:C:G	S247R	0.998
17:7701469:A:C	S248R	0.998
17:7701471:C:A	S248R	0.998
17:7701471:C:G	S248R	0.998
17:7700789:T:A	W231R	0.997
17:7700789:T:C	W231R	0.997
17:7701464:C:A	A246D	0.997
17:7703012:A:C	S430R	0.997
17:7703014:T:A	S430R	0.997
17:7703014:T:G	S430R	0.997
17:7689621:A:C	S188R	0.996
17:7689623:T:A	S188R	0.996
17:7689623:T:G	S188R	0.996
17:7689590:G:C	W177C	0.995
17:7689590:G:T	W177C	0.995
17:7703269:C:A	A477D	0.994
17:7701709:T:C	L292P	0.993
17:7701741:T:C	F303L	0.993
17:7701742:T:C	F303S	0.993
17:7701743:T:A	F303L	0.993
17:7701743:T:G	F303L	0.993
17:7689315:T:C	C175R	0.992
17:7700781:A:T	D228V	0.992
17:7701530:T:C	F268S	0.992
17:7701709:T:A	L292H	0.992

dbSNP variants (sampled 300 via entrez): RS1000133688 (17:7691021 C>A), RS1000299100 (17:7691322 G>T), RS1000314275 (17:7686758 G>A), RS1000743410 (17:7685736 C>G), RS1001107178 (17:7698186 G>A), RS1001274447 (17:7690117 T>G), RS1001374632 (17:7692230 A>G), RS1001506382 (17:7694543 A>G), RS1001977707 (17:7693523 G>A,C), RS1002040453 (17:7695038 C>G,T), RS1002108155 (17:7699869 G>T), RS1002241961 (17:7693225 G>C), RS1002579664 (17:7703129 T>A), RS1002589874 (17:7696372 C>A), RS1002591671 (17:7699819 C>CT)

Disease associations

OMIM: gene MIM:612661 | disease phenotypes: MIM:613988, MIM:127550

GenCC curated gene-disease

Disease	Classification	Inheritance
dyskeratosis congenita, autosomal recessive 3	Strong	Autosomal recessive
dyskeratosis congenita	Moderate	Unknown

ClinGen Gene-Disease Validity (3)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
dyskeratosis congenita, autosomal recessive 3	Moderate	AR
telomere syndrome	Moderate	SD
dyskeratosis congenita	Moderate	AR

Mondo (4): dyskeratosis congenita, autosomal recessive 3 (MONDO:0013520), dyskeratosis congenita (MONDO:0015780), hereditary neoplastic syndrome (MONDO:0015356), breast cancer (MONDO:0007254)

Orphanet (2): Dyskeratosis congenita (Orphanet:1775), Inherited cancer-predisposing syndrome (Orphanet:140162)

HPO phenotypes

67 total (30 of 67 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000035	Abnormal testis morphology
HP:0000164	Abnormality of the dentition
HP:0000327	Hypoplasia of the maxilla
HP:0000365	Hearing impairment
HP:0000498	Blepharitis
HP:0000499	Abnormal eyelash morphology
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000600	Abnormality of the pharynx
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000679	Taurodontia
HP:0000704	Periodontitis
HP:0000819	Diabetes mellitus
HP:0000939	Osteoporosis
HP:0000975	Hyperhidrosis
HP:0000982	Palmoplantar keratoderma
HP:0001000	Abnormality of skin pigmentation
HP:0001034	Hypermelanotic macule
HP:0001053	Hypopigmented skin patches
HP:0001231	Abnormal fingernail morphology
HP:0001263	Global developmental delay
HP:0001394	Cirrhosis
HP:0001399	Hepatic failure
HP:0001511	Intrauterine growth retardation
HP:0001596	Alopecia
HP:0001744	Splenomegaly
HP:0001873	Thrombocytopenia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004077_8	Cognitive function	7.000000e-07
GCST008757_28	Alcohol consumption	4.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D019871	Dyskeratosis Congenita	C15.378.190.223.500.750; C16.131.831.150; C16.320.322.108; C16.320.850.235; C17.800.804.150; C17.800.827.235
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066243 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1042522	TP53, WRAP53	3	5.00	2	antineoplastic agents;Platinum compounds

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Cadmium Chloride	decreases expression	2
FR900359	affects phosphorylation	1
bisphenol A	affects cotreatment, decreases expression	1
deoxynivalenol	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Caffeine	affects phosphorylation	1
Calcitriol	decreases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Indomethacin	affects cotreatment, decreases expression	1
Pesticides	increases abundance, increases methylation	1
Selenium	increases expression, affects cotreatment	1
Smoke	increases abundance, increases expression	1
Testosterone	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
Vitamin E	affects cotreatment, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5582328	Binding	Thermal stabilization of TCAB1 in human HL-60 cells at 10 uM incubated for 30 mins by CETSA	Small Molecules Blocking the Assembly of TCAB1 and Telomerase Complexes: Lead Discovery and Biological Activity. — ACS Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B5DG	HeLa1.3 hTR-50-3xMS2 TCAB1-/-	Cancer cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00014638	PHASE4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	PHASE4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	PHASE4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	PHASE4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	PHASE4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	PHASE4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	PHASE4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
NCT00131170	PHASE4	COMPLETED	Paravertebral Block for Breast Surgery
NCT00156039	PHASE4	COMPLETED	Randomized Trial of Follow-up Strategies in Breast Cancer
NCT00160901	PHASE4	COMPLETED	Complementary Therapies for the Reduction of Side Effects During Chemotherapy for Breast Cancer
NCT00171847	PHASE4	TERMINATED	Study of the Efficacy and Safety of Letrozole Combined With Trastuzumab in Patients With Metastatic Breast Cancer
NCT00176046	PHASE4	COMPLETED	Mistletoe Extract in Early or Advanced Breast Cancer, A Feasibility Study
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00234195	PHASE4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00237133	PHASE4	COMPLETED	Treatment of Locally Advanced Breast Cancer With Letrozole in Postmenopausal Women
NCT00237224	PHASE4	COMPLETED	Open Label Study of Postmenopausal Women With ER and /or PgR Positive Breast Cancer Treated With Letrozole
NCT00241046	PHASE4	TERMINATED	Letrozole in the Treatment of 1st and 2nd Line Hormone Receptor Positive Breast Cancer: Pre-therapeutic Risk Assessment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00323479	PHASE4	COMPLETED	Arthralgia During Anastrozole Therapy for Breast Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00356148	PHASE4	COMPLETED	The Efficacy of Prophylactic Antibiotic Administration During Breast Cancer Surgery in Overweight Patients.
NCT00372476	PHASE4	COMPLETED	Efficacy and Safety of Imatinib and Vinorelbine in Patients With Advanced Breast Cancer
NCT00413491	PHASE4	UNKNOWN	National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations
NCT00484614	PHASE4	UNKNOWN	Study the Role of Positron Emission Mammography in Pre-surgical Planning for Breast Cancer
NCT00485953	PHASE4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00531973	PHASE4	UNKNOWN	A Study of Liposomal Doxorubicin in Women With Breast Cancer Exploiting Tissue Doppler Imaging
NCT00537771	PHASE4	COMPLETED	Liver Safety Under Upfront Arimidex vs Tamoxifen
NCT00544986	PHASE4	COMPLETED	A Prospective,Open-label Study of Anastrozole in Post-menopausal Women With Hormone Sensitive Advanced Breast Cancer
NCT00613275	PHASE4	COMPLETED	Patient Navigation in the Safety Net:CONNECTeDD
NCT00638599	PHASE4	COMPLETED	Comparison of Laryngeal Mask Airway (LMA®) and Tracheal Tube in Modified Radical Mastectomy on Breast Cancer
NCT00647075	PHASE4	UNKNOWN	Yunzhi as Dietary Supplement in Breast Cancer
NCT00688909	PHASE4	COMPLETED	Rheumatological Evaluation of Anastrozole and Letrozole as Adjuvant Treatment in Post-menopausal Women With Breast Cancer
NCT00699101	PHASE4	TERMINATED	Using the Conture® Multi-Lumen Balloon to Deliver Accelerated Partial Breast Brachytherapy
NCT00742222	PHASE4	COMPLETED	Electronic Xoft Intersociety Brachytherapy Trial: Electronic Brachytherapy (EBT) For Treatment of Early Stage Breast Cancer
NCT00754767	PHASE4	TERMINATED	L-Carnitine L-Tartrate in Preventing Peripheral Neuropathy Caused By Chemotherapy in Women With Metastatic Breast Cancer