WRAP53

WD repeat containing antisense to TP53, the group of WD repeat domain containing

Basic information

Region (hg38): 17:7686071-7703502

Previous symbols: [ "WDR79" ]

Links

ENSG00000141499 ∙ NCBI:55135 ∙ OMIM:612661 ∙ HGNC:25522 ∙ Uniprot:Q9BUR4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dyskeratosis congenita, autosomal recessive 3 (Definitive), mode of inheritance: AR
• dyskeratosis congenita (Supportive), mode of inheritance: AD
• dyskeratosis congenita, autosomal recessive 3 (Moderate), mode of inheritance: AR
• dyskeratosis congenita, autosomal recessive 3 (Strong), mode of inheritance: AR
• dyskeratosis congenita (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dyskeratosis congenita, autosomal recessive 3	AR	Hematologic; Oncologic; Pulmonary	Surveillance (eg, with regularly performed CBC as well as other measures in the presence of concern for hematologic sequelae) for bone marrow failure, as well as surveillance for multiple cancer types (eg, with self-examination and clinical examination), and pulmonary disease may allow early detection and treatment; Lung transplant may be indicated in individuals with advanced lung diease; HSCT may be indicated due to manifestations including leukemia and bone marrow failure (which may also be treated with androgen therapy), but the long-term efficacy may not be optimal	Dermatologic; Hematologic; Oncologic; Pulmonary	21205863; 20301779

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WRAP53 gene.

• Hereditary cancer-predisposing syndrome (1 variants)
• Dyskeratosis congenita, autosomal recessive 3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WRAP53 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			2	103	1	106
missense	1	2	197	5	3	208
nonsense			2			2
start loss			1			1
frameshift	1	1	20			22
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			10	21		31
non coding			22	57	14	93
Total	2	3	246	165	18

Variants in WRAP53

This is a list of pathogenic ClinVar variants found in the WRAP53 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-7687108-C-T		Hereditary cancer-predisposing syndrome	Likely benign (Dec 01, 2015)
17-7687368-G-A		not specified	Likely benign (Oct 30, 2017)
17-7687372-C-A		Squamous cell carcinoma of the head and neck	Uncertain significance (May 28, 2019)
17-7687373-T-G			Uncertain significance (Dec 27, 2013)
17-7687375-AC-A		Hereditary cancer-predisposing syndrome	Uncertain significance (Nov 10, 2021)
17-7687376-C-A		Li-Fraumeni syndrome	Uncertain significance (Nov 09, 2023)
17-7687376-C-G		Li-Fraumeni syndrome • Hereditary cancer-predisposing syndrome	Conflicting classifications of pathogenicity (Oct 05, 2023)
17-7687376-C-T		Li-Fraumeni syndrome	Uncertain significance (Jan 18, 2024)
17-7687390-G-A			Uncertain significance (Apr 26, 2017)
17-7687391-C-A		Squamous cell carcinoma of the head and neck	Likely benign (May 28, 2019)
17-7687396-C-T		not specified	Uncertain significance (Jan 12, 2018)
17-7687421-G-T		Li-Fraumeni syndrome • Dyskeratosis Congenita, Recessive	Uncertain significance (Jun 14, 2016)
17-7687442-G-A		Dyskeratosis Congenita, Recessive • Li-Fraumeni syndrome 1	Uncertain significance (Apr 27, 2017)
17-7687450-G-C		Dyskeratosis Congenita, Recessive • Li-Fraumeni syndrome 1	Uncertain significance (Jan 12, 2018)
17-7687459-T-C		not specified	Uncertain significance (Nov 14, 2016)
17-7687471-G-A		Li-Fraumeni syndrome 1	Uncertain significance (Mar 30, 2018)
17-7688193-C-CG			Benign (May 25, 2021)
17-7688222-T-C			Likely benign (Feb 04, 2019)
17-7688236-G-A			Benign (Jul 05, 2018)
17-7688237-T-A			Benign (Jul 05, 2018)
17-7688335-T-G		Dyskeratosis Congenita, Recessive	Uncertain significance (Jun 14, 2016)
17-7688394-G-A		Dyskeratosis congenita, autosomal recessive 3	Uncertain significance (Jan 13, 2018)
17-7688404-G-C		Li-Fraumeni syndrome • Dyskeratosis congenita, autosomal recessive 3	Benign/Likely benign (Jan 13, 2018)
17-7688443-G-A		Li-Fraumeni syndrome • Dyskeratosis congenita, autosomal recessive 3	Benign/Likely benign (Jan 12, 2018)
17-7688501-C-T		Dyskeratosis congenita, autosomal recessive 3	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WRAP53	protein_coding	protein_coding	ENST00000316024	10	17432

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000535	0.999	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0202	315	316	0.997	0.0000199	3543
Missense in Polyphen		109	121.68	0.89582		1291
Synonymous	-0.0817	129	128	1.01	0.00000823	1129
Loss of Function	2.82	12	28.2	0.426	0.00000179	271

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000322	0.000322
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000929	0.0000924
European (Non-Finnish)	0.000238	0.000237
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: RNA chaperone that plays a key role in telomere maintenance and RNA localization to Cajal bodies (PubMed:29804836, PubMed:29695869). Specifically recognizes and binds the Cajal body box (CAB box) present in both small Cajal body RNAs (scaRNAs) and telomerase RNA template component (TERC) (PubMed:19285445, PubMed:20351177, PubMed:29804836, PubMed:29695869). Essential component of the telomerase holoenzyme complex, a ribonucleoprotein complex essential for the replication of chromosome termini that elongates telomeres in most eukaryotes (PubMed:19179534, PubMed:20351177, PubMed:26170453, PubMed:29695869). In the telomerase holoenzyme complex, required to stimulate the catalytic activity of the complex (PubMed:27525486, PubMed:29804836). 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 (PubMed:29804836). In addition, also controls telomerase holoenzyme complex localization to Cajal body (PubMed:22547674). During S phase, required for delivery of TERC to telomeres during S phase and for telomerase activity (PubMed:29804836). In addition to its role in telomere maintenance, also required for Cajal body formation, probably by mediating localization of scaRNAs to Cajal bodies (PubMed:19285445, PubMed:21072240). 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 (PubMed:25512560, PubMed:27715493). Acts by recruiting the ubiquitin ligase RNF8 to DNA breaks and promote both homologous recombination (HR) and non- homologous end joining (NHEJ) (PubMed:25512560, PubMed:27715493). {ECO:0000269|PubMed:19179534, ECO:0000269|PubMed:19285445, ECO:0000269|PubMed:20351177, ECO:0000269|PubMed:21072240, ECO:0000269|PubMed:22547674, ECO:0000269|PubMed:25512560, ECO:0000269|PubMed:26170453, ECO:0000269|PubMed:27525486, ECO:0000269|PubMed:27715493, ECO:0000269|PubMed:29695869, ECO:0000269|PubMed:29804836}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:21205863, ECO:0000269|PubMed:21602826}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Metabolism of proteins;Chaperonin-mediated protein folding;Association of TriC/CCT with target proteins during biosynthesis;Telomere Extension By Telomerase;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;Protein folding;Cell Cycle (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.759
• rvis_EVS: -0.57
• rvis_percentile_EVS: 18.9

Haploinsufficiency Scores

• pHI: 0.145
• hipred: N
• hipred_score: 0.435
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.649

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Wrap53
• Phenotype: immune system phenotype; hematopoietic system 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)

Gene ontology

• Biological process: DNA repair;telomere maintenance via telomerase;Cajal body organization;telomere formation via telomerase;RNA folding;positive regulation of DNA repair;positive regulation of telomerase activity;scaRNA localization to Cajal body;telomerase RNA localization to Cajal body;positive regulation of establishment of protein localization to telomere;protein localization to Cajal body;positive regulation of double-strand break repair via homologous recombination;positive regulation of double-strand break repair;positive regulation of double-strand break repair via nonhomologous end joining
• Cellular component: chromosome, telomeric region;nucleoplasm;telomerase holoenzyme complex;cytosol;Cajal body;nuclear body;site of double-strand break
• Molecular function: RNA binding;protein binding;ubiquitin protein ligase binding;histone binding;identical protein binding;protein-containing complex binding;chaperone binding;telomerase RNA binding