NAF1

nuclear assembly factor 1 ribonucleoprotein, the group of Ribosomal biogenesis factors

Basic information

Region (hg38): 4:163110073-163166890

Links

ENSG00000145414 ∙ NCBI:92345 ∙ OMIM:617868 ∙ HGNC:25126 ∙ Uniprot:Q96HR8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7	AD	Allergy/Immunology/Infectious; Hematologic; Pulmonary	The condition can involve immunologic manifestations, and awareness may allow early diagnosis and medical management (eg, with IVIG); Surveillance and prompt treatment of bone marrow failure may reduce morbidity; For treatment related to pulmonary fibrosis, early recognition may allow prompt medical management; HSCT has been described	Allergy/Immunology/Infectious; Dermatologic; Hematologic; Pulmonary	34767620

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NAF1 gene.

• not_provided (194 variants)
• not_specified (78 variants)
• NAF1-related_disorder (16 variants)
• Pulmonary_fibrosis (4 variants)
• Pulmonary_fibrosis_and/or_bone_marrow_failure_syndrome,_telomere-related,_7 (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NAF1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000138386.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	51	1	55
missense			148	8	4	160
nonsense		2	1			3
start loss						0
frameshift	2					2
splice donor/acceptor (+/-2bp)		2	2			4
Total	2	4	154	59	5

Highest pathogenic variant AF is 0.00000342031

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NAF1	protein_coding	protein_coding	ENST00000274054	8	56849

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.978	0.0221	125738	0	7	125745	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.310	264	250	1.06	0.0000119	3161
Missense in Polyphen		32	55.231	0.57938		709
Synonymous	-2.47	125	94.5	1.32	0.00000461	991
Loss of Function	3.79	2	20.5	0.0975	0.00000103	257

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000633	0.0000633
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000444	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: RNA-binding protein required for the maturation of box H/ACA snoRNPs complex and ribosome biogenesis. During assembly of the H/ACA snoRNPs complex, it associates with the complex and disappears during maturation of the complex and is replaced by NOLA1/GAR1 to yield mature H/ACA snoRNPs complex. Probably competes with NOLA1/GAR1 for binding with DKC1/NOLA4. {ECO:0000269|PubMed:16618814}.

Intolerance Scores

• loftool: 0.453
• rvis_EVS: 0.53
• rvis_percentile_EVS: 80.73

Haploinsufficiency Scores

• pHI: 0.151
• hipred: N
• hipred_score: 0.372
• ghis: 0.405

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.690

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Naf1
• 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); normal phenotype

Gene ontology

• Biological process: snoRNA guided rRNA pseudouridine synthesis;box H/ACA snoRNP assembly;positive regulation of telomere maintenance via telomerase;ribosome biogenesis;RNA stabilization;positive regulation of telomerase activity;telomerase RNA stabilization;positive regulation of telomere maintenance via telomere lengthening;positive regulation of telomerase RNA localization to Cajal body;telomerase holoenzyme complex assembly
• Cellular component: nucleus;small nucleolar ribonucleoprotein complex;cytoplasm
• Molecular function: RNA binding;protein binding;telomerase RNA binding