SNAP91

Chr 6

synaptosome associated protein 91

Also known as: AP180, CALM

NCBI Gene: 9892ENSG00000065609UniProt: O60641

Predicted to enable several functions, including clathrin adaptor activity; clathrin heavy chain binding activity; and phosphatidylinositol binding activity. Acts upstream of or within regulation of clathrin-dependent endocytosis. Predicted to be located in cytosol; postsynaptic density; and presynaptic membrane. Predicted to be active in several cellular components, including Schaffer collateral - CA1 synapse; cytoplasmic vesicle; and parallel fiber to Purkinje cell synapse. Predicted to be extrinsic component of presynaptic endocytic zone membrane. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2025]

147
ClinVar variants
13
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SNAP91
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 121 VUS of 147 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.19LOEUF
pLI 1.000
Z-score 5.44
OE 0.07 (0.03–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.16Z-score
OE missense 0.72 (0.65–0.79)
327 obs / 456.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.03–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.65–0.79)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 3 / 40.2Missense obs/exp: 327 / 456.8Syn Z: 1.16

ClinVar Variant Classifications

147 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
VUS121
Likely Benign4
Benign8
Conflicting1
13
Pathogenic
121
VUS
4
Likely Benign
8
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
0
0
0
VUS
1
104
16
0
121
Likely Benign
0
2
0
2
4
Benign
0
1
2
5
8
Conflicting
—1
Total1107317147

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

View in ClinVar →

Protein Context — Lollipop Plot

SNAP91 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Gene-level analysis reveals the genetic aetiology and therapeutic targets of schizophrenia.
Dang X et al.·Nat Hum Behav
2025Meta-analysis
Clinical significance and potential molecular mechanism of miRNA-222-3p in metastatic prostate cancer.
Sun Y et al.·Bioengineered
2021Functional
Analysis of high-risk pedigrees identifies 11 candidate variants for Alzheimer's disease.
Teerlink CC et al.·Alzheimers Dement
2022
Diverse mutations and structural variations contribute to Notch signaling deregulation in paediatric T-cell lymphoblastic lymphoma.
Salmerón-Villalobos J et al.·Pediatr Blood Cancer
2022
Insights Into the Antigenic Repertoire of Unclassified Synaptic Antibodies.
Gilligan M et al.·Ann Clin Transl Neurol
2026
Genome-wide association of mood-incongruent psychotic bipolar disorder.
Goes FS et al.·Transl Psychiatry
2012Meta-analysis
An alpha-helix variant p.Arg156Pro in LMNA as a cause of hereditary dilated cardiomyopathy: genetics and bioinfomatics exploration.
Chang L et al.·BMC Med Genomics
2023
Integrated Analysis of Whole Exome Sequencing and Copy Number Evaluation in Parkinson's Disease.
Yemni EA et al.·Sci Rep
2019
Screening for biomarkers of spermatogonia within the human testis: a whole genome approach.
von Kopylow K et al.·Hum Reprod
2010
Identification of a Seven-lncRNA-mRNA Signature for Recurrence and Prognostic Prediction in Relapsed Acute Lymphoblastic Leukemia Based on WGCNA and LASSO Analyses.
Qi H et al.·Anal Cell Pathol (Amst)
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools