NHP2

NHP2 ribonucleoprotein, the group of H/ACA ribonucleoprotein complex

Basic information

Region (hg38): 5:178149462-178153894

Previous symbols: [ "NOLA2" ]

Links

ENSG00000145912 ∙ NCBI:55651 ∙ OMIM:606470 ∙ HGNC:14377 ∙ Uniprot:Q9NX24 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dyskeratosis congenita (Supportive), mode of inheritance: AD
• dyskeratosis congenita (Limited), mode of inheritance: AR
• dyskeratosis congenita, autosomal recessive 2 (Strong), mode of inheritance: AR
• dyskeratosis congenita, autosomal recessive 2 (Moderate), mode of inheritance: AR
• dyskeratosis congenita, autosomal recessive 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dyskeratosis congenita, autosomal recessive 2	AR	Allergy/Immunology/Infectious; 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	Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic; Oncologic; Pulmonary	18523010; 20301779

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NHP2 gene.

• Dyskeratosis congenita (141 variants)
• not provided (19 variants)
• not specified (17 variants)
• Inborn genetic diseases (4 variants)
• Dyskeratosis congenita, autosomal recessive 1;Dyskeratosis congenita, autosomal recessive 2 (2 variants)
• Dyskeratosis congenita, autosomal recessive 2 (2 variants)
• Dyskeratosis Congenita, Recessive (1 variants)
• Dyskeratosis congenita, autosomal recessive 2;Dyskeratosis congenita, autosomal recessive 1 (1 variants)
• Dyskeratosis congenita, autosomal recessive 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NHP2 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				21		21
missense			65	2		67
nonsense						0
start loss			1			1
frameshift			9			9
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			4	6		10
non coding			3	33	5	41
Total	0	0	80	56	5

Variants in NHP2

This is a list of pathogenic ClinVar variants found in the NHP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-178149487-C-T			Likely benign (Feb 13, 2020)
5-178149702-A-T		not specified	Benign/Likely benign (May 06, 2019)
5-178149705-G-A		not specified	Uncertain significance (Oct 12, 2016)
5-178149715-A-C		Dyskeratosis congenita	Uncertain significance (Sep 01, 2022)
5-178149715-A-T		Dyskeratosis congenita, autosomal recessive 2 • Dyskeratosis congenita, autosomal recessive 1	Pathogenic (Aug 01, 2017)
5-178149719-G-T		Dyskeratosis congenita	Likely benign (Aug 23, 2022)
5-178149720-G-A		Dyskeratosis congenita	Uncertain significance (Oct 03, 2022)
5-178149726-G-T		Dyskeratosis congenita	Uncertain significance (Jun 03, 2022)
5-178149728-C-T		Dyskeratosis congenita	Likely benign (Sep 15, 2021)
5-178149734-C-A		Dyskeratosis congenita	Uncertain significance (Nov 06, 2023)
5-178149736-G-A		Dyskeratosis congenita	Uncertain significance (Jan 26, 2023)
5-178149736-G-T		Dyskeratosis congenita	Uncertain significance (Oct 13, 2023)
5-178149739-C-G		Dyskeratosis congenita	Uncertain significance (May 10, 2022)
5-178149741-T-A		Dyskeratosis congenita	Uncertain significance (Aug 19, 2022)
5-178149753-T-C		Dyskeratosis congenita	Uncertain significance (Mar 04, 2022)
5-178149757-C-T		Dyskeratosis congenita	Uncertain significance (Feb 16, 2022)
5-178149758-G-A		Dyskeratosis congenita	Likely benign (Oct 03, 2023)
5-178149760-A-G		Dyskeratosis congenita, autosomal recessive 2 • Dyskeratosis congenita, autosomal recessive 1	Pathogenic (Jun 10, 2008)
5-178149772-ACTC-A		Dyskeratosis congenita	Uncertain significance (Apr 02, 2019)
5-178149778-C-T		Dyskeratosis congenita	Uncertain significance (Aug 30, 2023)
5-178149779-A-ATGGGGCTT		Dyskeratosis congenita	Uncertain significance (Jan 22, 2018)
5-178149781-G-A		Dyskeratosis congenita • Dyskeratosis congenita, autosomal recessive 2	Uncertain significance (Aug 09, 2022)
5-178149784-G-T		Dyskeratosis congenita	Uncertain significance (Sep 04, 2023)
5-178149792-A-G		Dyskeratosis congenita	Uncertain significance (Aug 30, 2021)
5-178149797-C-T		Dyskeratosis congenita	Likely benign (Feb 10, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NHP2	protein_coding	protein_coding	ENST00000274606	4	4508

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0501	0.868	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0376	87	88.0	0.989	0.00000419	976
Missense in Polyphen		33	30.794	1.0716		379
Synonymous	0.00556	36	36.0	0.999	0.00000171	307
Loss of Function	1.44	3	7.15	0.419	3.92e-7	87

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000405	0.000405
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000220	0.000220
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000326	0.000326

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, 2 (DKCB2) [MIM:613987]: 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:18523010}. 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;Telomere Extension By Telomerase;Extension of Telomeres;Telomere Maintenance;Chromosome Maintenance;Cell Cycle;rRNA modification in the nucleus and cytosol;rRNA processing in the nucleus and cytosol (Consensus)

Recessive Scores

• pRec: 0.156

Intolerance Scores

• loftool: 0.729
• rvis_EVS: 0.42
• rvis_percentile_EVS: 76.81

Haploinsufficiency Scores

• pHI: 0.604
• hipred: Y
• hipred_score: 0.796
• ghis: 0.579

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.520

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nhp2
• Phenotype: skeleton 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); hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: cleavage involved in rRNA processing;maturation of LSU-rRNA;telomere maintenance via telomerase;rRNA pseudouridine synthesis;snRNA pseudouridine synthesis;positive regulation of telomerase RNA localization to Cajal body
• Cellular component: nuclear chromosome, telomeric region;nucleoplasm;telomerase holoenzyme complex;small nucleolar ribonucleoprotein complex;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