Human Gene Module / Chromosome 22 / CHKB

CHKBCholine kinase beta

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
5 / 11
Rare Variants / Common Variants
37 / 0
Aliases
CHKB, CHETK,  CHKL,  CK,  CKB,  CKEKB,  EK,  EKB,  MDCMC
Associated Syndromes
-
Chromosome Band
22q13.33
Associated Disorders
DD/NDD, ID, ASD, EPS
Relevance to Autism

Clinical characterization of 15 patients from 14 unrelated families with megaconial type congenital muscular dystrophy caused by CHKB mutations found that 8/15 patients presented with autistic features/behavioral problems (Haliloglu et al., 2015). A homozygous frameshift variant in CHKB was previously identifed in a patient with megaconial type congenital muscular dystrophy and a diagnosis of autistic spectrum disorder (Quinlivan et al., 2013). More recently, Bardhan et al. 2021 reported five children with megaconial type congenital muscular dystrophy from four Indian families, all of whom presented with autistic features and stereotypic hand movements; one of these patients was reported to have autistic spectrum disorder.

Molecular Function

The protein encoded by the CHKB gene catalyzes the first step in phosphatidylethanolamine biosynthesis and consequently plays as a key role in phospholipid biosynthesis. Homozygous or compound heterozygous mutations in this gene are responsible for megaconial type congenital muscular dystrophy (OMIM 602541).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CHKB (11 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Muscular dystrophy with large mitochondria associated with mutations in the CHKB gene in three British patients: extending the clinical and pathological phenotype Quinlivan R , et al. (2013) No ASD
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Primary Clinical characteristics of megaconial congenital muscular dystrophy due to choline kinase beta gene defects in a series of 15 patients Haliloglu G , et al. (2015) No DD, ID, autistic features
4 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
5 Support - Kutluk G et al. (Sep-) No ASD, DD, epilepsy/seizures
6 Support - Bardhan M et al. (2021) No Stereotypy
7 Support - Rhine CL et al. (2022) Yes -
8 Support - Zemorshidi F et al. (2023) No Autistic features, epilepsy/seizures
9 Support - Cirnigliaro M et al. (2023) Yes -
10 Support - Ruohao Wu et al. (2024) No -
11 Support - Mohammad-Reza Ghasemi et al. (2024) Yes DD, ID
Rare Variants   (37)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1031+1G>A - splice_site_variant Unknown - Simplex 33623274 Kutluk G et al. (Sep-)
c.1123C>T p.Gln375Ter stop_gained Unknown - Simplex 33712684 Bardhan M et al. (2021)
c.475C>T p.Arg159Ter stop_gained Unknown - Multiplex 26067811 Haliloglu G , et al. (2015)
c.1031+1G>A - splice_site_variant Unknown - Multiplex 26067811 Haliloglu G , et al. (2015)
c.1010A>G p.Asp337Gly missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.722A>G p.Asn241Ser missense_variant Unknown - Unknown 23692895 Quinlivan R , et al. (2013)
c.881C>G p.Pro294Arg missense_variant Unknown - Unknown 23692895 Quinlivan R , et al. (2013)
c.818+1G>A - splice_site_variant Familial Both parents Simplex 33623274 Kutluk G et al. (Sep-)
c.224+1G>T - splice_site_variant Familial Both parents Multiplex 33712684 Bardhan M et al. (2021)
c.151C>T p.Gln51Ter stop_gained Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1027dup p.Ser343LysfsTer86 frameshift_variant Unknown - Simplex 33712684 Bardhan M et al. (2021)
c.678-1G>C - splice_site_variant Familial Both parents Simplex 37393748 Zemorshidi F et al. (2023)
c.382G>T p.Glu128Ter stop_gained Familial Both parents Simplex 37393748 Zemorshidi F et al. (2023)
c.1031+1G>A - splice_site_variant Familial Both parents Simplex 26067811 Haliloglu G , et al. (2015)
c.1031+1G>A - splice_site_variant Familial Both parents Simplex 37393748 Zemorshidi F et al. (2023)
c.737-1G>C - splice_site_variant Familial Both parents Multiplex 37393748 Zemorshidi F et al. (2023)
c.581G>A p.Arg194Gln missense_variant Familial Both parents Simplex 33712684 Bardhan M et al. (2021)
c.922C>T p.Gln308Ter stop_gained Familial Both parents Multiplex 26067811 Haliloglu G , et al. (2015)
c.567_570del p.Phe189LeufsTer7 frameshift_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.722A>G p.Asn241Ser missense_variant Familial Both parents Simplex 23692895 Quinlivan R , et al. (2013)
c.847G>A p.Glu283Lys missense_variant Familial Both parents Simplex 26067811 Haliloglu G , et al. (2015)
c.392T>C p.Leu131Pro missense_variant Familial Both parents Simplex 37393748 Zemorshidi F et al. (2023)
c.539C>G p.Pro180Arg missense_variant Familial Both parents Simplex 37393748 Zemorshidi F et al. (2023)
c.722A>G p.Asn241Ser missense_variant Familial Both parents Simplex 37393748 Zemorshidi F et al. (2023)
c.1130G>T p.Arg377Leu missense_variant Familial Both parents Simplex 26067811 Haliloglu G , et al. (2015)
c.260T>C p.Leu87Pro missense_variant Familial Both parents Multiplex 37393748 Zemorshidi F et al. (2023)
c.668G>A p.Gly223Asp splice_site_variant Familial Both parents Simplex 26067811 Haliloglu G , et al. (2015)
c.1130G>T p.Arg377Leu missense_variant Familial Both parents Multiplex 37393748 Zemorshidi F et al. (2023)
c.382G>T p.Glu128Ter stop_gained Familial Both parents Simplex 39103847 Mohammad-Reza Ghasemi et al. (2024)
c.668G>A p.Gly223Asp splice_site_variant Familial Both parents Multiplex 26067811 Haliloglu G , et al. (2015)
c.598del p.Gln200ArgfsTer11 frameshift_variant Familial Both parents Simplex 38764027 Ruohao Wu et al. (2024)
c.852_859del p.Trp284Ter frameshift_variant Familial Both parents Simplex 23692895 Quinlivan R , et al. (2013)
c.611dup p.Thr205AsnfsTer5 frameshift_variant Familial Both parents Simplex 26067811 Haliloglu G , et al. (2015)
c.844dup p.Cys282LeufsTer2 frameshift_variant Familial Both parents Simplex 37393748 Zemorshidi F et al. (2023)
c.554_562del p.Pro185_Trp187del inframe_deletion Familial Both parents Simplex 26067811 Haliloglu G , et al. (2015)
c.554_562del p.Pro185_Trp187del inframe_deletion Familial Both parents Simplex 37393748 Zemorshidi F et al. (2023)
c.1007_1010del p.Glu336ValfsTer4 frameshift_variant Familial Both parents Simplex 26067811 Haliloglu G , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Clinical characterization of 15 patients from 14 unrelated families with megaconial type congenital muscular dystrophy caused by CHKB mutations found that 8/15 patients presented with autistic features/behavioral problems (PMID 26067811). A homozygous frameshift variant in CHKB was previously identifed in a patient with megaconial type congenital muscular dystrophy and a diagnosis of autistic spectrum disorder (PMID 23692895).

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

Clinical characterization of 15 patients from 14 unrelated families with megaconial type congenital muscular dystrophy caused by CHKB mutations found that 8/15 patients presented with autistic features/behavioral problems (PMID 26067811). A homozygous frameshift variant in CHKB was previously identifed in a patient with megaconial type congenital muscular dystrophy and a diagnosis of autistic spectrum disorder (PMID 23692895).

Reports Added
[Megaconial congenital muscular dystrophy secondary to novel CHKB mutations resemble atypical Rett syndrome2021]
1/1/2021
S
icon
S

Score remained at S

Description

Clinical characterization of 15 patients from 14 unrelated families with megaconial type congenital muscular dystrophy caused by CHKB mutations found that 8/15 patients presented with autistic features/behavioral problems (PMID 26067811). A homozygous frameshift variant in CHKB was previously identifed in a patient with megaconial type congenital muscular dystrophy and a diagnosis of autistic spectrum disorder (PMID 23692895).

Reports Added
[A Rare Cause of Autism Spectrum Disorder: Megaconial Muscular DystrophySep-]
10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Clinical characterization of 15 patients from 14 unrelated families with megaconial type congenital muscular dystrophy caused by CHKB mutations found that 8/15 patients presented with autistic features/behavioral problems (PMID 26067811). A homozygous frameshift variant in CHKB was previously identifed in a patient with megaconial type congenital muscular dystrophy and a diagnosis of autistic spectrum disorder (PMID 23692895).

Reports Added
[New Scoring Scheme]
4/1/2017
S
icon
S

Score remained at S

Description

Clinical characterization of 15 patients from 14 unrelated families with megaconial type congenital muscular dystrophy caused by CHKB mutations found that 8/15 patients presented with autistic features/behavioral problems (PMID 26067811). A homozygous frameshift variant in CHKB was previously identifed in a patient with megaconial type congenital muscular dystrophy and a diagnosis of autistic spectrum disorder (PMID 23692895).

Reports Added
[Clinical characteristics of megaconial congenital muscular dystrophy due to choline kinase beta gene defects in a series of 15 patients.2015] [Muscular dystrophy with large mitochondria associated with mutations in the CHKB gene in three British patients: extending the clinical and patholo...2013] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017]
1/1/2016
S
icon
S

Score remained at S

Description

Clinical characterization of 15 patients from 14 unrelated families with megaconial type congenital muscular dystrophy caused by CHKB mutations found that 8/15 patients presented with autistic features/behavioral problems (PMID 26067811). A homozygous frameshift variant in CHKB was previously identifed in a patient with megaconial type congenital muscular dystrophy and a diagnosis of autistic spectrum disorder (PMID 23692895).

Reports Added
[Clinical characteristics of megaconial congenital muscular dystrophy due to choline kinase beta gene defects in a series of 15 patients.2015] [Muscular dystrophy with large mitochondria associated with mutations in the CHKB gene in three British patients: extending the clinical and patholo...2013] [The contribution of de novo coding mutations to autism spectrum disorder2014]
Krishnan Probability Score

Score 0.40847790701437

Ranking 22941/25841 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 0.0006449714931485

Ranking 12063/18225 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 0.92746309999536

Ranking 10677/18665 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 -0.11634540679139

Ranking 12989/20870 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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