NANOS3
protein-codingnanos C2HC-type zinc finger 3, the group of Zinc fingers C2HC-type
Gene summary
Enables enzyme activator activity. Involved in germ cell development; mRNA destabilization; and negative regulation of translation. Located in cytosol; nucleoplasm; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: SD
Disease ID:MONDO:0005387
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NANOS3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001098622.3. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 24 | 2 | 26 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 25 | 2 | 0 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001092092.1 | 2 | MANE Select | |
| Ensembl | ENSP00000341992.4 | 2 | MANE Select | |
| Ensembl | ENSP00000380687.2 | 3 | Standard | |
| Ensembl | ENSP00000807966.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| nanos3 | Danio rerio | Structure: primordial germ cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of translation
- multicellular organism development
- germ cell development
- spermatogenesis
- negative regulation of translation
Molecular Function
- RNA binding
- protein binding
- zinc ion binding
Cellular Component
- P-body
- nucleus
- cytoplasm
- cytoplasmic stress granule
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000339133
- Coding exons
- 2
- Length
- 18695
- Individuals with no LoFs
- 125071
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125077
- p
- 0.0000240
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.35 | 81 | 123 | 0.657 | 0.00000825 | 1176 |
| Missense (PolyPhen) | 12 | 46.426 | 0.25848 | 441 | ||
| Synonymous | -1.38 | 69 | 55.8 | 1.24 | 0.00000402 | 427 |
| Loss of Function | 1.29 | 3 | 6.55 | 0.458 | 4.54e-7 | 60 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in the maintenance of the undifferentiated state of germ cells regulating the spermatogonia cell cycle and inducing a prolonged transit in G1 phase. Affects cell proliferation probably by repressing translation of specific mRNAs. Maintains the germ cell lineage by suppressing both Bax- dependent and -independent apoptotic pathways. Essential in the early stage embryo to protect the migrating primordial germ cells (PGCs) from apoptosis. {ECO:0000269|PubMed:21421998}.;
Recessive Scores
- pRec
- 0.262
Intolerance Scores
- LoFtool
- 0.470
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.137
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |