CASK

Protein identityUniProt · HPA

UniProt accession

O14936

Gene

CASK

Ensembl

ENSG00000147044

Chromosome

X

Canonical length

926 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Nucleoplasm,Cytosol

OverviewNCBI Gene

This gene encodes a calcium/calmodulin-dependent serine protein kinase. The encoded protein is a MAGUK (membrane-associated guanylate kinase) protein family member. These proteins are scaffold proteins and the encoded protein is located at synapses in the brain. Mutations in this gene are associated with FG syndrome 4, intellectual disability and microcephaly with pontine and cerebellar hypoplasia, and a form of X-linked intellectual disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

Canonical amino-acid sequenceUniProt

926 residues, UniProt reviewed canonical sequence.

>O14936|CASK
     1  MADDDVLFED VYELCEVIGK GPFSVVRRCI NRETGQQFAV KIVDVAKFTS SPGLSTEDLK
    61  REASICHMLK HPHIVELLET YSSDGMLYMV FEFMDGADLC FEIVKRADAG FVYSEAVASH
   121  YMRQILEALR YCHDNNIIHR DVKPHCVLLA SKENSAPVKL GGFGVAIQLG ESGLVAGGRV
   181  GTPHFMAPEV VKREPYGKPV DVWGCGVILF ILLSGCLPFY GTKERLFEGI IKGKYKMNPR
   241  QWSHISESAK DLVRRMLMLD PAERITVYEA LNHPWLKERD RYAYKIHLPE TVEQLRKFNA
   301  RRKLKGAVLA AVSSHKFNSF YGDPPEELPD FSEDPTSSGL LAAERAVSQV LDSLEEIHAL
   361  TDCSEKDLDF LHSVFQDQHL HTLLDLYDKI NTKSSPQIRN PPSDAVQRAK EVLEEISCYP
   421  ENNDAKELKR ILTQPHFMAL LQTHDVVAHE VYSDEALRVT PPPTSPYLNG DSPESANGDM
   481  DMENVTRVRL VQFQKNTDEP MGITLKMNEL NHCIVARIMH GGMIHRQGTL HVGDEIREIN
   541  GISVANQTVE QLQKMLREMR GSITFKIVPS YRTQSSSCER DSPSTSRQSP ANGHSSTNNS
   601  VSDLPSTTQP KGRQIYVRAQ FEYDPAKDDL IPCKEAGIRF RVGDIIQIIS KDDHNWWQGK
   661  LENSKNGTAG LIPSPELQEW RVACIAMEKT KQEQQASCTW FGKKKKQYKD KYLAKHNAVF
   721  DQLDLVTYEE VVKLPAFKRK TLVLLGAHGV GRRHIKNTLI TKHPDRFAYP IPHTTRPPKK
   781  DEENGKNYYF VSHDQMMQDI SNNEYLEYGS HEDAMYGTKL ETIRKIHEQG LIAILDVEPQ
   841  ALKVLRTAEF APFVVFIAAP TITPGLNEDE SLQRLQKESD ILQRTYAHYF DLTIINNEID
   901  ETIRHLEEAV ELVCTAPQWV PVSWVY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CASK can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.33

Highest tissue expression

30 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CASK.

Disease | AllUniProt

Conditions CASK is implicated in, by any mechanism.

• Intellectual developmental disorder with microcephaly and pontine and cerebellar hypoplasia (MICPCH) MIM:300749
• FG syndrome 4 (FGS4) MIM:300422

Disease | GeneticClinVar

203 pathogenic / likely-pathogenic of 1,097 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Syndromic X-linked intellectual disability Najm type
• Intellectual disability, CASK-related, X-linked
• FG syndrome 4
• Inborn genetic diseases
• CASK-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.07

gnomAD pLI

1

gnomAD missense Z

4.25

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• calcium ion import
• cell adhesion
• establishment of localization in cell
• intracellular protein localization
• negative regulation of cell-matrix adhesion
• negative regulation of cellular response to growth factor stimulus
• negative regulation of keratinocyte proliferation
• negative regulation of wound healing
• positive regulation of calcium ion import
• positive regulation of transcription by RNA polymerase II
• regulation of neurotransmitter secretion
• regulation of synaptic vesicle exocytosis

Molecular functions

• ATP binding
• calmodulin binding
• GMP kinase activity
• neurexin family protein binding
• protein serine kinase activity
• protein serine/threonine kinase activity
• signaling receptor binding

Cellular components

• actin cytoskeleton
• basement membrane
• basolateral plasma membrane
• cell-cell junction
• ciliary membrane
• cytoplasm
• cytosol
• focal adhesion
• nuclear lamina
• nuclear matrix
• nucleolus
• plasma membrane
• presynaptic membrane
• Schaffer collateral - CA1 synapse
• vesicle

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• SH3 domain
• PDZ domain
• L27 domain
• Guanylate kinase-like domain
• Guanylate kinase/L-type calcium channel beta subunit
• Protein kinase-like domain superfamily
• L27 domain, C-terminal
• Guanylate kinase, conserved site
• P-loop containing nucleoside triphosphate hydrolase
• SH3-like domain superfamily
• PDZ superfamily
• L27 domain superfamily
• Membrane-associated guanylate kinase
• Protein kinase domain
• PDZ domain
• Guanylate kinase
• L27 domain
• Variant SH3 domain
• CASK, SH3 domain

KeywordsUniProt

• ATP-binding
• Calmodulin-binding
• Cell membrane
• Cytoplasm
• Intellectual disability
• Kinase
• Membrane
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Repeat
• Serine/threonine-protein kinase
• SH3 domain
• Transferase

InteractionsUniProt · HPA

Protein binding partners of CASK in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• APBA1
• CASKIN1
• FCHSD2
• KIRREL3
• LIN7
• TBR1
• TSPYL2
• WHRN
• CADM3
• ID1
• LIN7A
• RPH3A
• SDC2
• SH2D4A
• SNTB2
• TIAM1