Postsynaptic adhesion molecule that binds to presynaptic neurexins to mediate synapse formation, and which is involved in learning and memory (By similarity). Promotes synapse development by acting as a cell adhesion molecule at the postsynaptic membrane, which associates with neurexin-alpha at the presynaptic membrane (By similarity)

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 0.59
Clinical SummaryCLSTN2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.59LOEUF
pLI 0.000
Z-score 3.67
OE 0.40 (0.270.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.68Z-score
OE missense 0.92 (0.850.99)
511 obs / 556.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.40 (0.270.59)
00.351.4
Missense OE?0.92 (0.850.99)
00.61.4
Synonymous OE?1.09
01.21.6
LoF obs/exp: 17 / 42.9Missense obs/exp: 511 / 556.1Syn Z: -1.04

This gene — mechanism propensity

DN
0.6842th %ile
GOF
0.6443th %ile
LOF
0.3355th %ile

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

DNprediction above median
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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CLSTN2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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