SHISA6
protein-codingshisa family member 6, the group of Shisa family members
Gene summary
Predicted to enable ionotropic glutamate receptor binding activity. Predicted to be involved in several processes, including excitatory chemical synaptic transmission; negative regulation of canonical Wnt signaling pathway; and regulation of short-term neuronal synaptic plasticity. Predicted to be located in asymmetric, glutamatergic, excitatory synapse. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in dendritic spine membrane; postsynaptic density; and postsynaptic membrane. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~322.9 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 SHISA6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_207386.4. 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 | 0 | |||||
| missense | 110 | 110 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 111 | 0 | 0 | 111 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_997269.2 | 6 | MANE Select | |
| Ensembl | ENSP00000390084.3 | 6 | MANE Select | |
| RefSeq | NP_001166932.1 | 4 | Standard | |
| RefSeq | NP_001166933.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- spermatogenesis
- Wnt signaling pathway
- regulation of short-term neuronal synaptic plasticity
- negative regulation of canonical Wnt signaling pathway
- regulation of postsynaptic neurotransmitter receptor activity
Molecular Function
- PDZ domain binding
- ionotropic glutamate receptor binding
Cellular Component
- postsynaptic density
- cell junction
- AMPA glutamate receptor complex
- dendritic spine membrane
- synapse
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000441885
- Coding exons
- 6
- Length
- 322801
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.15 | 197 | 302 | 0.652 | 0.0000192 | 3488 |
| Missense (PolyPhen) | 120 | 191.06 | 0.62806 | 1939 | ||
| Synonymous | 0.704 | 122 | 132 | 0.922 | 0.00000900 | 1158 |
| Loss of Function | 3.46 | 3 | 19.5 | 0.154 | 9.94e-7 | 235 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in maintenance of high-frequency synaptic transmission at hippocampal CA3-CA1 synapses. Regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression. May play a role in self-renewal and differentiation of spermatogonial stem cells by inhibiting canonical Wnt signaling pathway. {ECO:0000250|UniProtKB:Q3UH99}.;
Intolerance Scores
- RVIS EVS
- 0.57
- RVIS percentile EVS
- 81.89
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |