CLSTN3

Chr 12

calsyntenin 3

Also known as: CDHR14, CSTN3, alcbeta

NCBI Gene: 9746 ENSG00000139182 UniProt: Q9BQT9 OMIM: 611324

CLSTN3 encodes a postsynaptic adhesion molecule that binds to presynaptic neurexins to mediate both excitatory and inhibitory synapse formation and regulates the balance between these synapse types. Mutations cause autosomal dominant neurodevelopmental disorders affecting cognitive function and behavior. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to have significant clinical consequences.

OMIM ResearchSummary from RefSeq, UniProt

Enables cell-cell adhesion mediator activity and neurexin family protein binding activity. Involved in L-ascorbic acid metabolic process and regulation of synapse assembly. Predicted to be located in several cellular components, including Golgi membrane; postsynaptic density; and postsynaptic membrane. Predicted to be part of protein-containing complex. Predicted to be active in several cellular components, including endoplasmic reticulum membrane; lipid droplet; and postsynaptic density membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.32

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.32LOEUF

pLI 0.970

Z-score 4.98

OE 0.17 (0.09–0.32)

Highly constrained

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

Missense Constraint?

1.50Z-score

OE missense 0.83 (0.77–0.89)

487 obs / 589.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.17 (0.09–0.32)

0≤0.351.4

Missense OE?0.83 (0.77–0.89)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 7 / 41.7Missense obs/exp: 487 / 589.3Syn Z: -0.17

Background carrier burden — how many people carry a rare variant somewhere in CLSTN3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 35

1,381 rare PASS variants

Rare truncating (LoF)

1 in 340

115 rare PASS variants

Rare synonymous (reference)

1 in 54

592 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CLSTN3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 42	1 in 760
South Asian	~43k	1 in 32	1 in 480
Remaining (unassigned)	~30k	1 in 28	1 in 510
European (Finnish)	~27k	1 in 75	1 in 5,200
Admixed American	~22k	1 in 31	1 in 350
African / African American	~21k	1 in 28	1 in 360
East Asian	~20k	1 in 34	1 in 640
Ashkenazi Jewish	~13k	1 in 110	1 in 1,300
Middle Eastern	~2,884	1 in 30	≈ 1 in 700

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 18 coding exons well covered in gnomAD exomes and genomes.? see exons ↓