SPAG9
protein-codingsperm associated antigen 9
Gene summary
This gene encodes a member of the cancer testis antigen gene family. The encoded protein functions as a scaffold protein that structurally organizes mitogen-activated protein kinases and mediates c-Jun-terminal kinase signaling. This protein also binds to kinesin-1 and may be involved in microtubule-based membrane transport. This protein may play a role in tumor growth and development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~158.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005090
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SPAG9 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001130528.3. 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 | 2 | 1 | 3 | 6 | ||
| missense | 139 | 3 | 142 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 148 | 4 | 3 | 155 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001124000.1 | 30 | MANE Select | |
| Ensembl | ENSP00000262013.7 | 30 | MANE Select | |
| RefSeq | NP_001123999.1 | 30 | Standard | |
| RefSeq | NP_001238900.1 | 27 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- EGF-Ncore
- Developmental Biology
- CDO in myogenesis
- Myogenesis
- Arf6 trafficking events
Biological Process
- activation of JUN kinase activity
- vesicle-mediated transport
- positive regulation of cell migration
- retrograde transport, endosome to Golgi
- positive regulation of neuron differentiation
Molecular Function
- MAP-kinase scaffold activity
- protein binding
- JUN kinase binding
- kinesin binding
- receptor signaling complex scaffold activity
Cellular Component
- acrosomal vesicle
- cytoplasm
- microtubule organizing center
- cytosol
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262013
- Coding exons
- 30
- Length
- 158692
- Individuals with no LoFs
- 125738
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125748
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.13 | 479 | 715 | 0.670 | 0.0000370 | 8651 |
| Missense (PolyPhen) | 102 | 217.98 | 0.46793 | 2449 | ||
| Synonymous | 1.18 | 234 | 258 | 0.907 | 0.0000136 | 2507 |
| Loss of Function | 7.43 | 5 | 74.0 | 0.0676 | 0.00000393 | 896 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Isoform 5 may play a role in spermatozoa-egg- interaction. {ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:15693750}.;
Recessive Scores
- pRec
- 0.200
Intolerance Scores
- LoFtool
- 0.399
- RVIS EVS
- -1.13
- RVIS percentile EVS
- 6.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.979
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |