SPAG6
protein-codingsperm associated antigen 6, the group of Armadillo repeat containing|Cilia and flagella associated
Gene summary
The correlation of anti-sperm antibodies with cases of unexplained infertility implicates a role for these antibodies in blocking fertilization. Improved diagnosis and treatment of immunologic infertility, as well as identification of proteins for targeted contraception, are dependent on the identification and characterization of relevant sperm antigens. The protein expressed by this gene is recognized by anti-sperm antibodies from an infertile man. This protein localizes to the tail of permeabilized human sperm and contains eight contiguous armadillo repeats, a motif known to mediate protein-protein interactions. Studies in mice suggest that this protein is involved in sperm flagellar motility and maintenance of the structural integrity of mature sperm. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~108.8 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 SPAG6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012443.4. 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 | 3 | 2 | 1 | 6 | ||
| missense | 61 | 1 | 62 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 65 | 3 | 1 | 69 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036575.1 | 11 | MANE Select | |
| Ensembl | ENSP00000365811.3 | 11 | MANE Select | |
| RefSeq | NP_001240783.1 | 10 | Standard | |
| RefSeq | NP_001240784.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- spermatid development
- cell projection organization
Cellular Component
- nucleus
- microtubule
- axoneme
- microtubule cytoskeleton
- motile cilium
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000376624
- Coding exons
- 11
- Length
- 108755
- Individuals with no LoFs
- 125678
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 70
- Defined
- 125748
- p
- 0.000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.743 | 238 | 273 | 0.873 | 0.0000136 | 3274 |
| Missense (PolyPhen) | 60 | 75.33 | 0.7965 | 986 | ||
| Synonymous | -0.688 | 114 | 105 | 1.09 | 0.00000582 | 1038 |
| Loss of Function | 0.674 | 22 | 25.7 | 0.857 | 0.00000135 | 305 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.0010 | 0.0010 | notable |
| Finnish | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.00026 | 0.00025 | rare |
| South Asian | 0.00024 | 0.00023 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Important for structural integrity of the central apparatus in the sperm tail and for flagellar motility. {ECO:0000250, ECO:0000269|PubMed:10493827}.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- LoFtool
- 0.770
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.66
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.278
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |