NOP10

NOP10 ribonucleoprotein, the group of H/ACA ribonucleoprotein complex

Basic information

Region (hg38): 15:34339158-34343180

Previous symbols: [ "NOLA3" ]

Links

ENSG00000182117 ∙ NCBI:55505 ∙ OMIM:606471 ∙ HGNC:14378 ∙ Uniprot:Q9NPE3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dyskeratosis congenita, autosomal recessive 1 (Limited), mode of inheritance: AR
• dyskeratosis congenita, autosomal recessive 1 (Limited), mode of inheritance: AR
• dyskeratosis congenita (Supportive), mode of inheritance: AD
• dyskeratosis congenita, autosomal recessive 1 (Strong), mode of inheritance: AR
• pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9; Dyskeratosis congenita, autosomal recessive 1; Cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 2	AD/AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Gastrointestinal; Hematologic; Oncologic; Pulmonary; Renal	Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related can involve hepatic manifestations, and awareness may allow early diagnosis and medical and surgical management; Surveillance and prompt treatment of findings related to hematologic sequelae (including risk of malignancy) may be beneficial; For treatment related to pulmonary fibrosis, early recognition may allow prompt medical management; In Dyskeratosis congenita, autosomal recessive 1, 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; Cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 2 can involve early-onset hearing loss and renal disease, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Identification and management of renal sequelae may be beneficial	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Dental; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic; Oncologic; Pulmonary; Renal	17507419; 20301779; 32139460; 32554502

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NOP10 gene.

• Dyskeratosis congenita, autosomal recessive 1 (53 variants)
• not provided (20 variants)
• not specified (10 variants)
• Dyskeratosis Congenita, Recessive (6 variants)
• Agenesis of the corpus callosum with peripheral neuropathy (3 variants)
• Hereditary cancer-predisposing syndrome (3 variants)
• Dyskeratosis congenita (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NOP10 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				5		5
missense			19	1		20
nonsense			1			1
start loss						0
frameshift			4			4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			11	11	9	31
Total	0	0	35	17	9

Variants in NOP10

This is a list of pathogenic ClinVar variants found in the NOP10 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-34341784-T-C		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (Jan 12, 2018)
15-34341796-A-C		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (Jan 13, 2018)
15-34341819-C-T		Agenesis of the corpus callosum with peripheral neuropathy • Dyskeratosis Congenita, Recessive • Dyskeratosis congenita, autosomal recessive 1	Benign/Likely benign (Nov 27, 2018)
15-34341832-A-G		Dyskeratosis Congenita, Recessive • Agenesis of the corpus callosum with peripheral neuropathy • Dyskeratosis congenita, autosomal recessive 1	Benign/Likely benign (Nov 12, 2018)
15-34341836-A-C		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (Jan 13, 2018)
15-34341839-C-T		Agenesis of the corpus callosum with peripheral neuropathy • Dyskeratosis congenita, autosomal recessive 1 • Dyskeratosis Congenita, Recessive	Benign/Likely benign (Feb 28, 2019)
15-34341860-A-G		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (Jan 13, 2018)
15-34341888-G-A		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (Jan 13, 2018)
15-34341923-C-G		Dyskeratosis congenita, autosomal recessive 1 • not specified	Benign (Jan 24, 2024)
15-34341926-A-AG		Dyskeratosis Congenita, Recessive	Conflicting classifications of pathogenicity (Jan 10, 2019)
15-34341937-G-A		Dyskeratosis congenita, autosomal recessive 1 • not specified	Benign (Jan 24, 2024)
15-34341938-T-C		Dyskeratosis congenita, autosomal recessive 1 • not specified	Benign (Jan 24, 2024)
15-34341978-G-A		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (Jun 22, 2022)
15-34341982-G-A		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (May 15, 2022)
15-34341984-G-A		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (Sep 05, 2023)
15-34341990-T-C		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (Aug 17, 2022)
15-34341998-G-A		Dyskeratosis congenita, autosomal recessive 1	Likely benign (Oct 14, 2023)
15-34342002-A-C		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (Dec 25, 2022)
15-34342007-G-C		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (Mar 18, 2020)
15-34342009-A-G		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (Sep 20, 2021)
15-34342012-G-A		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (May 11, 2023)
15-34342013-T-C		Dyskeratosis congenita, autosomal recessive 1	Likely benign (Nov 08, 2022)
15-34342021-T-TG		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (Mar 14, 2020)
15-34342028-TCGGTGTCGAGAGT-GGTG		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (Dec 20, 2021)
15-34342035-C-T		Dyskeratosis congenita, autosomal recessive 1	Uncertain significance (Jul 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NOP10	protein_coding	protein_coding	ENST00000328848	2	1462

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.769	0.223	125731	0	4	125735	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.317	33	38.5	0.856	0.00000258	409
Missense in Polyphen		8	9.8308	0.81377		137
Synonymous	0.969	10	14.7	0.679	8.12e-7	126
Loss of Function	2.04	0	4.86	0.00	3.63e-7	37

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)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for ribosome biogenesis and telomere maintenance. Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine ("psi") residues, which may serve to stabilize the conformation of rRNAs. May also be required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme. {ECO:0000269|PubMed:15044956}.
• Disease: DISEASE: Dyskeratosis congenita, autosomal recessive, 1 (DKCB1) [MIM:224230]: 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:17507419}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ribosome biogenesis in eukaryotes - Homo sapiens (human);rRNA processing;Metabolism of RNA;rRNA modification in the nucleus and cytosol;rRNA processing in the nucleus and cytosol (Consensus)

Intolerance Scores

• loftool: 0.343
• rvis_EVS: 0.3
• rvis_percentile_EVS: 71.81

Haploinsufficiency Scores

• pHI: 0.426
• hipred: Y
• hipred_score: 0.602
• ghis: 0.420

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.955

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nop10

Zebrafish Information Network

• Gene name: nop10
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: snoRNA guided rRNA pseudouridine synthesis;pseudouridine synthesis;telomere maintenance via telomerase;rRNA pseudouridine synthesis;snRNA pseudouridine synthesis;positive regulation of telomerase RNA localization to Cajal body
• Cellular component: nucleoplasm;telomerase holoenzyme complex;small nucleolar ribonucleoprotein complex;nuclear body;box H/ACA snoRNP complex;box H/ACA scaRNP complex;box H/ACA telomerase RNP complex
• Molecular function: RNA binding;protein binding;box H/ACA snoRNA binding;telomerase RNA binding