SHISA9

Chr 16

shisa family member 9

Also known as: CKAMP44

NCBI Gene: 729993ENSG00000237515UniProt: B4DS77OMIM: 613346

The protein regulates short-term neuronal synaptic plasticity by associating with AMPA glutamate receptors in synaptic spines and promoting their desensitization at excitatory synapses. The gene is highly constrained against loss-of-function variants (pLI 0.87, LOEUF 0.41), but no established human disease associations have been reported to date.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.41
Clinical Summary— SHISA9
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 72 VUS of 93 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.873
Z-score 3.18
OE 0.13 (0.05–0.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.79Z-score
OE missense 0.68 (0.59–0.77)
164 obs / 242.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.13 (0.05–0.41)
0≤0.351.4
Missense OE0.68 (0.59–0.77)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 2 / 15.5Missense obs/exp: 164 / 242.4Syn Z: 0.73
DN
0.5378th %ile
GOF
0.6443th %ile
LOF
0.68top 10%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.41
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

93 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic2
VUS72
Likely Benign3
14
Pathogenic
2
Likely Pathogenic
72
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
2
0
2
VUS
0
61
11
0
72
Likely Benign
0
2
1
0
3
Benign
0
0
0
0
0
Total06328091

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SHISA9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients