NVL
protein-codingnuclear VCP like, the group of MicroRNA protein coding host genes|AAA ATPases
Gene summary
This gene encodes a member of the AAA (ATPases associated with diverse cellular activities) superfamily. Multiple transcript variants encoding different isoforms have been found for this gene. Two encoded proteins, described as major and minor isoforms, have been localized to distinct regions of the nucleus. The largest encoded protein (major isoform) has been localized to the nucleolus and shown to participate in ribosome biosynthesis (PMID: 15469983, 16782053), while the minor isoform has been localized to the nucleoplasmin. [provided by RefSeq, Aug 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~102.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NVL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002533.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 2 | 6 | |||
| missense | 83 | 7 | 90 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 90 | 9 | 0 | 99 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002524.2 | 23 | MANE Select | |
| Ensembl | ENSP00000281701.6 | 23 | MANE Select | |
| RefSeq | NP_001230075.1 | 18 | Standard | |
| RefSeq | NP_001230076.1 | 22 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ribosome biogenesis in eukaryotes - Homo sapiens (human)
Biological Process
- rRNA processing
- positive regulation of protein binding
- ribosome biogenesis
- ribosomal large subunit biogenesis
- positive regulation of telomerase activity
Molecular Function
- RNA binding
- protein binding
- ATP binding
- ATPase activity
- preribosome binding
Cellular Component
- nuclear exosome (RNase complex)
- nucleus
- nucleoplasm
- telomerase holoenzyme complex
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000281701
- Coding exons
- 23
- Length
- 103054
- Individuals with no LoFs
- 125636
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 111
- Defined
- 125747
- p
- 0.000441
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.59 | 366 | 462 | 0.792 | 0.0000242 | 5560 |
| Missense (PolyPhen) | 108 | 174.09 | 0.62037 | 1935 | ||
| Synonymous | 0.394 | 158 | 164 | 0.961 | 0.00000836 | 1680 |
| Loss of Function | 2.01 | 37 | 52.7 | 0.702 | 0.00000325 | 587 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.00067 | 0.00067 | rare |
| Ashkenazi Jewish | 0.00079 | 0.00079 | rare |
| East Asian | 0.00077 | 0.00060 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00034 | 0.00034 | rare |
| South Asian | 0.00059 | 0.00059 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Participates in the assembly of the telomerase holoenzyme and effecting of telomerase activity via its interaction with TERT (PubMed:22226966). Involved in both early and late stages of the pre-rRNA processing pathways (PubMed:26166824). Spatiotemporally regulates 60S ribosomal subunit biogenesis in the nucleolus (PubMed:15469983, PubMed:16782053, PubMed:29107693, PubMed:26456651). Catalyzes the release of specific assembly factors, such as WDR74, from pre-60S ribosomal particles through the ATPase activity (PubMed:29107693, PubMed:26456651, PubMed:28416111). {ECO:0000269|PubMed:15469983, ECO:0000269|PubMed:16782053, ECO:0000269|PubMed:22226966, ECO:0000269|PubMed:26166824, ECO:0000269|PubMed:26456651, ECO:0000269|PubMed:28416111, ECO:0000269|PubMed:29107693}.;
Recessive Scores
- pRec
- 0.119
Intolerance Scores
- LoFtool
- 0.127
- RVIS EVS
- 0.56
- RVIS percentile EVS
- 81.67
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.701
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |