STRA8
protein-codingstimulated by retinoic acid 8
Gene summary
This gene encodes a retinoic acid-responsive protein. A homologous protein in mouse has been shown to be involved in the regulation of meiotic initiation in both spermatogenesis and oogenesis, though feature differences between the mouse and human proteins suggest that these homologs are not entirely functionally equivalent. It is thought that this gene may play a role in spermatogenesis in humans. [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 ~26.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0018393
Submitter: King Faisal Specialist Hospital and Research Center
Alhathal et al., 2020 (PMID: 32719396) reported a LOF variant in a large male infertility cohort (n=285 infertile man and case–control fertile man). Gene is scored according to ClinGen classification. Moderate with total score of 8. Single variant segregation (3 points), experimental evidence: Animal model (4 points) and testicular expression (1 points) (PMID: 33400349).
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to STRA8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001394401.1. 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 | 1 | 1 | 2 | |||
| missense | 31 | 1 | 32 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 32 | 2 | 0 | 34 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001381330.1 | 8 | MANE Select | |
| Ensembl | ENSP00000499386.1 | 8 | MANE Select | |
| RefSeq | NP_872295.2 | 8 | Standard | |
| Ensembl | ENSP00000275764.3 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- DNA replication
- positive regulation of transcription by RNA polymerase II
- male germ-line stem cell asymmetric division
- oogenesis
- meiotic cell cycle
Molecular Function
- protein dimerization activity
Cellular Component
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000275764
- Coding exons
- 9
- Length
- 26514
- Individuals with no LoFs
- 125718
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 30
- Defined
- 125748
- p
- 0.000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.28 | 144 | 194 | 0.741 | 0.0000114 | 2186 |
| Missense (PolyPhen) | 32 | 52.668 | 0.60758 | 637 | ||
| Synonymous | 1.73 | 60 | 79.6 | 0.753 | 0.00000503 | 610 |
| Loss of Function | 2.04 | 8 | 17.1 | 0.468 | 8.99e-7 | 179 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00087 | 0.00082 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Meiosis-inducer required for the transition into meiosis for both female and male germ cells. In female germ cells, required for premeiotic DNA replication and subsequent events in meiotic prophase. During spermatogenesis, next to its role in meiotic initiation, promotes (but is not required for) spermatogonial differentiation. Can associate with DNA (possibly in an indirect manner), and in vitro can activate DNA transcription (By similarity). {ECO:0000250|UniProtKB:P70278}.;
Recessive Scores
- pRec
- 0.149
Intolerance Scores
- LoFtool
- 0.426
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 64.11
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0894
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |