CLSTN2

Chr 3

calsyntenin 2

Also known as: ALC-GAMMA, CDHR13, CS2, CSTN2, alcagamma

NCBI Gene: 64084 ENSG00000158258 UniProt: Q9H4D0 OMIM: 611323

Predicted to enable cell-cell adhesion mediator activity. Predicted to be involved in homophilic cell-cell adhesion; positive regulation of synapse assembly; and positive regulation of synaptic transmission. Predicted to be located in several cellular components, including Golgi membrane; postsynaptic density; and postsynaptic membrane. Predicted to be active in cell surface and postsynaptic density membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.59

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.59LOEUF

pLI 0.000

Z-score 3.67

OE 0.40 (0.27–0.59)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.68Z-score

OE missense 0.92 (0.85–0.99)

511 obs / 556.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.27–0.59)

0≤0.351.4

Missense OE?0.92 (0.85–0.99)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 17 / 42.9Missense obs/exp: 511 / 556.1Syn Z: -1.04

Background carrier burden — how many people carry a rare variant somewhere in CLSTN2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 43

1,240 rare PASS variants

Rare truncating (LoF)

1 in 2,300

117 rare PASS variants

Rare synonymous (reference)

1 in 74

516 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CLSTN2. 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 62	1 in 2,200
South Asian	~43k	1 in 34	1 in 1,200
Remaining (unassigned)	~30k	1 in 32	≈ 1 in 15,000
European (Finnish)	~27k	1 in 280	1 in 3,000
Admixed American	~22k	1 in 46	≈ 1 in 11,000
African / African American	~21k	1 in 42	1 in 2,000
East Asian	~20k	1 in 41	1 in 1,200
Ashkenazi Jewish	~13k	1 in 150	1 in 1,500
Middle Eastern	~2,884	1 in 42	≈ 1 in 2,800

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): 16 of 17 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 17.? see exons ↓