DOK7

Protein identityUniProt · HPA

UniProt accession

Q18PE1

Gene

DOK7

Ensembl

ENSG00000175920

Chromosome

4

Canonical length

504 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Nucleoplasm,Mitochondria

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is essential for neuromuscular synaptogenesis. The protein functions in aneural activation of muscle-specific receptor kinase, which is required for postsynaptic differentiation, and in the subsequent clustering of the acetylcholine receptor in myotubes. This protein can also induce autophosphorylation of muscle-specific receptor kinase. Mutations in this gene are a cause of familial limb-girdle myasthenia autosomal recessive, which is also known as congenital myasthenic syndrome type 1B. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

Canonical amino-acid sequenceUniProt

504 residues, UniProt reviewed canonical sequence.

>Q18PE1|DOK7
     1  MTEAALVEGQ VKLRDGKKWK SRWLVLRKPS PVADCLLMLV YKDKSERIKG LRERSSLTLE
    61  DICGLEPGLP YEGLVHTLAI VCLSQAIMLG FDSHEAMCAW DARIRYALGE VHRFHVTVAP
   121  GTKLESGPAT LHLCNDVLVL ARDIPPAVTG QWKLSDLRRY GAVPSGFIFE GGTRCGYWAG
   181  VFFLSSAEGE QISFLFDCIV RGISPTKGPF GLRPVLPDPS PPGPSTVEER VAQEALETLQ
   241  LEKRLSLLSH AGRPGSGGDD RSLSSSSSEA SHLDVSASSR LTAWPEQSSS SASTSQEGPR
   301  PAAAQAAGEA MVGASRPPPK PLRPRQLQEV GRQSSSDSGI ATGSHSSYSS SLSSYAGSSL
   361  DVWRATDELG SLLSLPAAGA PEPSLCTCLP GTVEYQVPTS LRAHYDTPRS LCLAPRDHSP
   421  PSQGSPGNSA ARDSGGQTSA GCPSGWLGTR RRGLVMEAPQ GSEATLPGPA PGEPWEAGGP
   481  HAGPPPAFFS ACPVCGGLKV NPPP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DOK7 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)

0.51

Highest tissue expression

43 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DOK7.

Disease | AllUniProt

Conditions DOK7 is implicated in, by any mechanism.

• Myasthenic syndrome, congenital, 10 (CMS10) MIM:254300
• Fetal akinesia deformation sequence 3 (FADS3) MIM:618389

Disease | GeneticClinVar

149 pathogenic / likely-pathogenic of 1,335 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital myasthenic syndrome 10
• Fetal akinesia deformation sequence 1
• Fetal akinesia deformation sequence 3
• Congenital myasthenic syndrome
• DOK7-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)

0.93

gnomAD pLI

0

gnomAD missense Z

-2.55

DepMap mean gene effect

0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• enzyme-linked receptor protein signaling pathway
• neuromuscular junction development
• neurotransmitter receptor localization to postsynaptic specialization membrane
• positive regulation of protein tyrosine kinase activity
• positive regulation of Rac protein signal transduction
• positive regulation of skeletal muscle acetylcholine-gated channel clustering
• Rac protein signal transduction
• receptor clustering

Molecular functions

• phosphatidylinositol binding
• protein kinase binding
• signaling adaptor activity

Cellular components

• mitochondrion
• neuromuscular junction
• nucleoplasm
• postsynaptic membrane

Protein domainsUniProt · Pfam · InterPro

• Pleckstrin homology domain
• IRS-type PTB domain
• PH-like domain superfamily
• PTB domain (IRS-1 type)
• Protein Dok-7
• Dok-7, PH domain
• Dok-7, PTB domain

KeywordsUniProt

• Cell membrane
• Congenital myasthenic syndrome
• Lipid-binding
• Membrane
• Synapse

InteractionsUniProt · HPA

Protein binding partners of DOK7 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MUSK