GeneBe

NAF1

protein-coding

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

Gene summary

Enables identical protein binding activity and telomerase RNA binding activity. Involved in ribosome biogenesis; telomerase RNA stabilization; and telomerase holoenzyme complex assembly. Acts upstream of or within telomerase RNA localization to Cajal body. Located in cytosol and nucleoplasm. Part of sno(s)RNA-containing ribonucleoprotein complex. Implicated in melanoma. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_138386.3

Inheritance

AD

ClinVar variants

P:5U:190B:84

Top phenotype

Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr4:163,110,073-163,166,890

External References & Databases

Ensembl (ENSG00000145414)NCBI Gene (92345)OMIM (617868)HGNC:25126GenCCUniProt (Q96HR8)AlphaFoldClinVar (NAF1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~56.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0957261

Submitter: Labcorp Genetics (formerly Invitae)

pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0957261

Submitter: ClinGen

*NAF1*, nuclear assembly factor 1 ribonucleoprotein, encodes a box H/ACA RNA biogenesis factor which intervenes in early assembly steps of human box H/ACA RNPs, including telomerase (PMID: 16601202). *NAF1* was firstly reported in relation to pulmonary fibrosis in 2016 (Stanley et al., PMID: 27510903). The report described two frameshift mutations (K319Rfs*21 and S329Ifs*12 ) in two unrelated females with pulmonary fibrosis and bone marrow failure/ myelodysplasia. The reported variants were segregated with short telomere phenotype and low TR levels. An additional 11 (frameshift, splice site, inframe deletion and missense) variants were reported in the two retrospective cohort studies (Alder et al., (2021) PMID: 34933798 and Zhang et al., (2022) PMID: 36028256) that sequenced patients with Idiopathic Pulmonary Fibrosis (IPF) or IPF/Familial Pulmonary Fibrosis, respectively. Experimental evidence also supports this gene-disease relationship. Western blot of NAF1 in LCLs derived from mutation carriers detected a lower–molecular weight species similar to those detected by Myc-tagging NAF1 at an isogenic doxycycline-inducible locus in HeLa cells. Immunofluorescence showed a nuclear localization defect of NAF1 in the mutated cells (PMID: 27510903). *Naf1+/− *mice showed decreased TR levels, similar to *TR+/−* animals. Levels of H/ACA small nucleolar RNAs (snoRNAs) and a small Cajal body RNA were also reduced (PMID: 27510903). In summary, *NAF1* is definitively associated with autosomal dominant pulmonary fibrosis and/or bone marrow failure, Telomere-related. This has been repeatedly demonstrated in both research and diagnostic settings and has been upheld over time.

pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0957261

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7AD

Manifestation: Allergy/Immunology/Infectious; Dermatologic; Hematologic; Pulmonary

Intervention: Allergy/Immunology/Infectious; Hematologic; Pulmonary

Rationale: 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

Refs: 34767620Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NAF1 variants in ClinVar

5 Conditions Cataloged
not providedTotal: 250
not specifiedTotal: 112
NAF1-related disorderTotal: 25
Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7Total: 6
Pulmonary fibrosisTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138386.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
4
clinvar
68
clinvar
1
clinvar
 73
missense
178
clinvar
12
clinvar
3
clinvar
 193
nonsense
1
clinvar
4
clinvar
 5
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
2
clinvar
4
clinvar
 6
Total23190804279

Highest pathogenic variant AF is 0.0000034203094

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_138386.3RefSeqNP_612395.28MANE Select
ENST00000274054.3EnsemblENSP00000274054.28MANE Select
NM_001128931.2RefSeqNP_001122403.18Standard
ENST00000422287.6EnsemblENSP00000408963.28Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • snoRNA guided rRNA pseudouridine synthesis
  • box H/ACA snoRNP assembly
  • positive regulation of telomere maintenance via telomerase
  • ribosome biogenesis
  • RNA stabilization

Molecular Function

  • RNA binding
  • protein binding
  • telomerase RNA binding

Cellular Component

  • nucleus
  • small nucleolar ribonucleoprotein complex
  • cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000274054
Coding exons
8
Length
56849
Individuals with no LoFs
125738
Homozygous LoFs
0
Heterozygous LoFs
7
Defined
125745
p
0.0000278
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.3102642501.060.00001193161
Missense (PolyPhen)3255.2310.57938709
Synonymous-2.4712594.51.320.00000461991
Loss of Function3.79220.50.09750.00000103257

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000630.000058rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000440.000044rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.690

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.