CAMK2B

Chr 7AD

calcium/calmodulin dependent protein kinase II beta

Also known as: CAM2, CAMK2, CAMKB, CaMKIIbeta, MRD54

NCBI Gene: 816 ENSG00000058404 UniProt: Q13554 OMIM: 607707

The protein encodes the beta subunit of calcium/calmodulin-dependent protein kinase II, a serine/threonine kinase essential for calcium signaling and synaptic plasticity at glutamatergic synapses. Mutations cause autosomal dominant intellectual developmental disorder, autosomal dominant 54. The low LOEUF score (0.364) indicates the gene is highly intolerant to loss-of-function variants, suggesting haploinsufficiency as the likely pathogenic mechanism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The product of this gene belongs to the serine/threonine protein kinase family and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells, the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a beta chain. It is possible that distinct isoforms of this chain have different cellular localizations and interact differently with calmodulin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 54MIM #617799

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Intellectual developmental disorder, autosomal dominant 54; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.36

LOEUF

LOF*

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

0.36LOEUF

pLI 0.739

Z-score 4.65

OE 0.20 (0.12–0.36)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

4.07Z-score

OE missense 0.42 (0.37–0.48)

166 obs / 393.1 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.20 (0.12–0.36)

0≤0.351.4

Missense OE?0.42 (0.37–0.48)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 8 / 39.6Missense obs/exp: 166 / 393.1Syn Z: 0.22

Background carrier burden — how many people carry a rare variant somewhere in CAMK2B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 63

729 rare PASS variants

Rare truncating (LoF)

1 in 220

104 rare PASS variants

Rare synonymous (reference)

1 in 65

453 rare PASS variants

Rare missense and truncating variants are carried at similar rates in CAMK2B; this gene does not show strong loss-of-function constraint by this measure. 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 92	1 in 230
South Asian	~43k	1 in 62	1 in 610
Remaining (unassigned)	~30k	1 in 72	1 in 980
European (Finnish)	~27k	1 in 260	1 in 2,600
Admixed American	~22k	1 in 110	1 in 460
African / African American	~21k	1 in 110	1 in 1,500
East Asian	~20k	1 in 94	1 in 370
Ashkenazi Jewish	~13k	1 in 270	≈ 1 in 2,700
Middle Eastern	~2,884	1 in 110	≈ 1 in 850

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): 19 of 23 coding exons well covered in gnomAD exomes; exons 1, 18, 19, 20 marginal. Genomes: 20 of 23 (exons 1, 5, 20 below).? see exons ↓