Human Gene Module / Chromosome 7 / CAMK2B

CAMK2Bcalcium/calmodulin dependent protein kinase II beta

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
3 / 13
Rare Variants / Common Variants
19 / 0
Aliases
CAMK2B, CAM2,  CAMK2,  CAMKB
Associated Syndromes
-
Chromosome Band
7p13
Associated Disorders
DD/NDD, ID, EP, EPS, ASD
Relevance to Autism

Kury et al., 2017 reported 10 individuals with intellectual disability that were found to carry de novo variants in the CAMK2B gene, many of which were experimentally shown to have either loss-of-function or gain-of-function effects; three of these individuals also presented with ASD/autistic features.

Molecular Function

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.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CAMK2B (13 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability Kry S , et al. (2017) No ASD or autistic features
2 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
3 Support De novo variants in CAMK2A and CAMK2B cause neurodevelopmental disorders Akita T , et al. (2018) No Epilepsy/seizures
4 Recent Recommendation A novel role for CAMKII? in the regulation of cortical neuron migration: implications for neurodevelopmental disorders Nicole O , et al. (2018) No -
5 Support Variant recurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense variants Lecoquierre F , et al. (2019) No -
6 Support Severe intellectual disability, absence of language, epilepsy, microcephaly and progressive cerebellar atrophy related to the recurrent de novo variant p.(P139L) of the CAMK2B gene: A case report and brief review Rizzi S et al. (2020) No DD, ID, epilepsy/seizures, stereotypy
7 Support - Heiman P et al. (2021) No Autosomal dominant mental retardation-54 (MRD54)
8 Support - Krgovic D et al. (2022) Yes DD, ID
9 Support - Zhou X et al. (2022) Yes -
10 Support - Sanchis-Juan A et al. (2023) No -
11 Support - Tamam Khalaf et al. (2024) No -
12 Support - Axel Schmidt et al. (2024) No -
13 Support - Katherynn K Zhang et al. (2024) No -
Rare Variants   (19)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.85C>T p.Arg29Ter stop_gained De novo - - 29100089 Kry S , et al. (2017)
c.820-1G>A - splice_site_variant De novo - - 29100089 Kry S , et al. (2017)
c.903+1G>A - splice_site_variant De novo - - 29100089 Kry S , et al. (2017)
c.85C>T p.Arg29Ter stop_gained Unknown - - 39039281 Axel Schmidt et al. (2024)
c.328G>A p.Glu110Lys missense_variant De novo - - 29100089 Kry S , et al. (2017)
c.416C>T p.Pro139Leu missense_variant De novo - - 29100089 Kry S , et al. (2017)
c.709G>A p.Glu237Lys missense_variant De novo - - 29100089 Kry S , et al. (2017)
c.901A>G p.Lys301Glu missense_variant De novo - - 29100089 Kry S , et al. (2017)
c.416C>T p.Pro139Leu missense_variant De novo - - 32875707 Rizzi S et al. (2020)
c.944C>G p.Ser315Ter stop_gained Unknown - - 38438125 Tamam Khalaf et al. (2024)
c.638C>T p.Pro213Leu missense_variant De novo - - 29560374 Akita T , et al. (2018)
c.852A>T p.Arg284Ser missense_variant De novo - - 29560374 Akita T , et al. (2018)
c.328G>A p.Glu110Lys missense_variant Unknown - - 35813072 Krgovic D et al. (2022)
c.199_200delinsTA p.Leu67Tyr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.416C>T p.Pro139Leu missense_variant De novo - - 31036916 Lecoquierre F , et al. (2019)
c.1991C>T p.Pro664Leu missense_variant De novo - Simplex 29346770 Takata A , et al. (2018)
c.85C>T p.Arg29Ter stop_gained Familial Maternal Multiplex 33796307 Heiman P et al. (2021)
c.416C>T p.Pro139Leu missense_variant Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
c.416C>T p.Pro139Leu missense_variant De novo - Simplex 39113374 Katherynn K Zhang et al. (2024)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Kury et al., 2017 reported 10 individuals with intellectual disability that were found to carry de novo variants in the CAMK2B gene, many of which were experimentally shown to have either loss-of-function or gain-of-function effects; three of these individuals also presented with ASD/autistic features.

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2021
S
icon
S

Score remained at S

Description

Kury et al., 2017 reported 10 individuals with intellectual disability that were found to carry de novo variants in the CAMK2B gene, many of which were experimentally shown to have either loss-of-function or gain-of-function effects; three of these individuals also presented with ASD/autistic features.

Reports Added
[A familial case of CAMK2B mutation with variable expressivity2021]
7/1/2020
S
icon
S

Score remained at S

Description

Kury et al., 2017 reported 10 individuals with intellectual disability that were found to carry de novo variants in the CAMK2B gene, many of which were experimentally shown to have either loss-of-function or gain-of-function effects; three of these individuals also presented with ASD/autistic features.

Reports Added
[Severe intellectual disability, absence of language, epilepsy, microcephaly and progressive cerebellar atrophy related to the recurrent de novo variant p.(P139L) of the CAMK2B gene: A case report and 2020]
10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Kury et al., 2017 reported 10 individuals with intellectual disability that were found to carry de novo variants in the CAMK2B gene, many of which were experimentally shown to have either loss-of-function or gain-of-function effects; three of these individuals also presented with ASD/autistic features.

Reports Added
[New Scoring Scheme]
7/1/2019
S
icon
S

Score remained at S

Description

Kury et al., 2017 reported 10 individuals with intellectual disability that were found to carry de novo variants in the CAMK2B gene, many of which were experimentally shown to have either loss-of-function or gain-of-function effects; three of these individuals also presented with ASD/autistic features.

Reports Added
[Variantrecurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense v...2019]
Krishnan Probability Score

Score 0.76560674844625

Ranking 11/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.46862019409236

Ranking 5623/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.94540328211814

Ranking 16456/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.51727002105531

Ranking 393/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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