TDRD1
protein-codingtudor domain containing 1, the group of Tudor domain containing|Zinc fingers MYND-type
Gene summary
This gene encodes a protein containing a tudor domain that is thought to function in the suppression of transposable elements during spermatogenesis. The related protein in mouse forms a complex with piRNAs and Piwi proteins to promote methylation and silencing of target sequences. This gene was observed to be upregulated by ETS transcription factor ERG in prostate tumors. [provided by RefSeq, Sep 2018]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~53.4 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 TDRD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001395205.1. 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 | 2 | 2 | ||||
| missense | 1 | 126 | 10 | 1 | 138 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 126 | 12 | 1 | 140 |
Highest pathogenic variant AF is 0.000002478281
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001382134.1 | 24 | MANE Select | |
| Ensembl | ENSP00000511878.1 | 24 | MANE Select | |
| RefSeq | NP_001352820.1 | 24 | Standard | |
| RefSeq | NP_001372292.1 | 25 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tdrd1 | Danio rerio | Structure: primordial germ cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene expression (Transcription)
- PIWI-interacting RNA (piRNA) biogenesis
- Gene Silencing by RNA
Biological Process
- multicellular organism development
- germ cell development
- spermatogenesis
- gene silencing by RNA
- piRNA metabolic process
Molecular Function
- metal ion binding
Cellular Component
- cytoplasm
- chromatoid body
- P granule
- pi-body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000251864
- Coding exons
- 25
- Length
- 53035
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125742
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.40 | 509 | 606 | 0.840 | 0.0000293 | 7821 |
| Missense (PolyPhen) | 196 | 273.03 | 0.71786 | 3655 | ||
| Synonymous | -1.59 | 247 | 217 | 1.14 | 0.0000114 | 2158 |
| Loss of Function | 6.59 | 5 | 60.1 | 0.0832 | 0.00000280 | 820 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| 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 central role during spermatogenesis by participating in the repression transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Required for the localization of Piwi proteins to the meiotic nuage. Involved in the piRNA metabolic process by ensuring the entry of correct transcripts into the normal piRNA pool and limiting the entry of cellular transcripts into the piRNA pathway. May act by allowing the recruitment of piRNA biogenesis or loading factors that ensure the correct entry of transcripts and piRNAs into Piwi proteins (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0927
Intolerance Scores
- LoFtool
- 0.411
- RVIS EVS
- -0.52
- RVIS percentile EVS
- 20.94
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.810
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |