GNL3
protein-codingG protein nucleolar 3, the group of Small nucleolar RNA protein coding host genes
Gene summary
The protein encoded by this gene may interact with p53 and may be involved in tumorigenesis. The encoded protein also appears to be important for stem cell proliferation. This protein is found in both the nucleus and nucleolus. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.3 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 GNL3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014366.5. 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 | 6 | 6 | ||||
| missense | 72 | 10 | 82 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 84 | 10 | 0 | 94 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055181.3 | 15 | MANE Select | |
| Ensembl | ENSP00000395772.1 | 15 | MANE Select | |
| RefSeq | NP_996561.1 | 14 | Standard | |
| RefSeq | NP_996562.1 | 14 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| gnl3 | Danio rerio | Structure: radial glial cell Quality: disorganized abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ribosome biogenesis in eukaryotes - Homo sapiens (human)
Biological Process
- cell population proliferation
- stem cell division
- stem cell population maintenance
- positive regulation of telomere maintenance
- positive regulation of protein sumoylation
Molecular Function
- RNA binding
- protein binding
- GTP binding
- mRNA 5'-UTR binding
Cellular Component
- extracellular space
- nucleus
- nucleolus
- membrane
- nuclear body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000418458
- Coding exons
- 15
- Length
- 13337
- Individuals with no LoFs
- 125660
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 88
- Defined
- 125748
- p
- 0.000350
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.283 | 272 | 285 | 0.953 | 0.0000137 | 3628 |
| Missense (PolyPhen) | 61 | 87.494 | 0.69719 | 1186 | ||
| Synonymous | -1.50 | 118 | 99.1 | 1.19 | 0.00000484 | 985 |
| Loss of Function | 0.349 | 30 | 32.1 | 0.934 | 0.00000164 | 387 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00062 | 0.00062 | rare |
| Latino/Admixed American | 0.00049 | 0.00049 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00036 | 0.00036 | rare |
| South Asian | 0.00030 | 0.00029 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be required to maintain the proliferative capacity of stem cells. Stabilizes MDM2 by preventing its ubiquitination, and hence proteasomal degradation (By similarity). {ECO:0000250, ECO:0000269|PubMed:12464630, ECO:0000269|PubMed:16012751}.;
Recessive Scores
- pRec
- 0.174
Intolerance Scores
- LoFtool
- 0.951
- RVIS EVS
- 0.8
- RVIS percentile EVS
- 87.59
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.855
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |