SPAG17
protein-codingsperm associated antigen 17
Gene summary
This gene encodes a central pair protein present in the axonemes of cells with a "9 + 2" organization of microtubules. The encoded protein is required for the proper function of the axoneme. Mutations in the orthologous gene in mice lead to primary ciliary dyskinesia characterized by immotile nasal and tracheal cilia, reduced clearance of nasal mucus, profound respiratory distress, hydrocephalus, and neonatal lethality within twelve hours of birth due to impaired airway mucociliary clearance. Single-nucleotide polymorphisms in this gene are associated with human height and targeted mutations lead to skeletal malformations affecting the limbs in mice, suggesting a role for this gene in skeletal development. [provided by RefSeq, Feb 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~231.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0017173
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0030307
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0030307
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0018393
Submitter: King Faisal Specialist Hospital and Research Center
Alhathal et al., 2020 (PMID: 32719396) reported a missense variant in a large male infertility cohort (n=285 infertile man and case–control fertile man). Gene is scored according to ClinGen classification. Moderate based on, reported in male infertility (PMID: 28548327). Animal model (Spag17tm1b(KOMP)Wtsi). Expression (PMID:15827353)/ (>1 independent study with several unrelated probands with pathogenic variants, supporting experimental data and no contradictory evidences).
Clinical Genomic Database (CGD)
Manifestation: Genitourinary
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SPAG17 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_206996.4. 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 | 20 | 2 | 25 | ||
| missense | 1 | 1 | 278 | 28 | 6 | 314 |
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 1 | 1 | 290 | 48 | 8 | 348 |
Highest pathogenic variant AF is 0.000038425067
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_996879.1 | 48 | MANE Select | |
| Ensembl | ENSP00000337804.5 | 48 | MANE Select | |
| Ensembl | ENSP00000402749.1 | 17 | Standard | |
| Ensembl | ENSP00000800496.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- epithelial cilium movement
- axonemal central apparatus assembly
Cellular Component
- microtubule
- motile cilium
- axonemal central apparatus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000336338
- Coding exons
- 48
- Length
- 231363
- Individuals with no LoFs
- 125509
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 238
- Defined
- 125748
- p
- 0.000951
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0798 | 1126 | 1.13e+3 | 0.993 | 0.0000561 | 14678 |
| Missense (PolyPhen) | 349 | 378.69 | 0.9216 | 5116 | ||
| Synonymous | 0.250 | 381 | 387 | 0.984 | 0.0000194 | 4041 |
| Loss of Function | 5.00 | 60 | 119 | 0.505 | 0.00000585 | 1545 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0022 | 0.0022 | notable |
| Latino/Admixed American | 0.0017 | 0.0017 | notable |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00059 | 0.00054 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00071 | 0.00068 | rare |
| South Asian | 0.0022 | 0.0016 | notable |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the central pair apparatus of ciliary axonemes. Plays a critical role in the function and structure of motile cilia. May play a role in endochondral bone formation, most likely because of a function in primary cilia of chondrocytes and osteoblasts. {ECO:0000250|UniProtKB:Q5S003}.;
Intolerance Scores
- LoFtool
- 0.981
- RVIS EVS
- 0.6
- RVIS percentile EVS
- 82.88
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.101
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |