NAF1: Nuclear Assembly Factor 1 Ribonucleoprotein
A key regulator of telomerase RNA biogenesis and H/ACA snoRNP assembly
Gene Information Card
| Symbol | NAF1 |
|---|---|
| Full Name | Nuclear Assembly Factor 1 Ribonucleoprotein |
| Gene Type | Protein coding |
| Chromosomal Location | 4q32.2 |
| NCBI Gene ID | 92345 ncbi.nlm.nih.gov/gene/92345 |
| Ensembl ID | ENSG00000145431 |
| UniProt ID | Q96HR8 |
| OMIM ID | 614798 |
| HGNC ID | 25036 |
| Aliases | DKCB5, FLJ10613, MGC131809, NAF-1 |
Description
NAF1 encodes a nuclear assembly factor essential for the biogenesis of H/ACA small nucleolar ribonucleoproteins (snoRNPs) and the telomerase RNP. It binds to the H/ACA RNA motif and facilitates the assembly of core proteins, including dyskerin (DKC1), NHP2, NOP10, and GAR1. NAF1 is critical for telomerase RNA (TERC) stability and telomere maintenance. Mutations in NAF1 cause dyskeratosis congenita and pulmonary fibrosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dyskeratosis congenita, autosomal dominant 5 (DKCB5) | Loss-of-function mutations reduce TERC levels, impairing telomerase activity and telomere maintenance | ClinVar, OMIM #614798 |
| Idiopathic pulmonary fibrosis (IPF) | Heterozygous NAF1 mutations lead to telomere shortening in alveolar epithelial cells, increasing susceptibility to fibrosis | ClinVar, NCBI |
| Hoyeraal-Hreidarsson syndrome | Severe telomere dysfunction due to compound heterozygous NAF1 variants | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Bone marrow | 8.7 | Medium |
| Lung | 5.2 | Low |
| Skin | 4.1 | Low |
| Liver | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.5 | Embryonic kidney, high expression |
| HeLa | 8.9 | Cervical carcinoma, moderate |
| A549 | 6.3 | Lung carcinoma, moderate |
| K562 | 4.7 | Leukemia, low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100C>T (p.Arg34*) | Nonsense | Rare | Premature truncation, loss of function |
| c.349G>A (p.Gly117Arg) | Missense | Rare | Impaired H/ACA RNA binding |
| c.544_545del (p.Gln182Valfs*5) | Frameshift | Rare | Loss of protein function |
Mutation functional classification
Loss of Function (LOF)
Most NAF1 mutations are loss-of-function, reducing TERC levels and telomerase activity.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Heterozygous mutations may act via haploinsufficiency; dominant-negative effects not established.
View complete mutation data：
Gene Ontology (GO)
| • nucleolus (GO:0005730) | • nucleoplasm (GO:0005654) |
| • intracellular ribonucleoprotein complex (GO:0030529) | • RNA binding (GO:0003723) |
| • mRNA processing (GO:0006397) | • RNA modification (GO:0009451) |
| • telomere maintenance via telomerase (GO:0007004) |
Pathways
• Telomere maintenance (Reactome: R-HSA-157579)
• rRNA modification in the nucleus and cytosol (Reactome: R-HSA-6790901)
• H/ACA snoRNP assembly (Reactome: R-HSA-6790901)
Protein Summary
NAF1 is a 464-amino-acid nuclear protein that acts as a molecular chaperone for H/ACA snoRNP assembly. It directly binds the H/ACA RNA motif and recruits dyskerin, NHP2, NOP10, and GAR1. After assembly, NAF1 is replaced by the retention factor NOP10, allowing mature snoRNPs to function. In telomerase biogenesis, NAF1 is essential for TERC stability and telomere elongation. Loss of NAF1 function leads to telomere shortening and is associated with dyskeratosis congenita and pulmonary fibrosis.
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