DOK7 docking protein 7 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DOK7provided by HGNC
Official Full Name: docking protein 7provided by HGNC
Primary source: HGNC:HGNC:26594
See related: Ensembl:ENSG00000175920 MIM:610285; Vega:OTTHUMG00000122087
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CMS10; CMS1B; C4orf25
Summary: 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]
Expression: Biased expression in heart (RPKM 3.1), testis (RPKM 1.0) and 9 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 4p16.3

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	4	NC_000004.12 (3463306..3501476)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (3465033..3503203)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Silencing DNMT3A inhibits proliferation and invasion in ESCC cells by inducing demethylation of DOK7.
Title: Repression of DOK7 mediated by DNMT3A promotes the proliferation and invasion of KYSE410 and TE-12 ESCC cells.
DOK7 was reduced in lung cancer and reduced DOK7 expression was associated with poorer survival.DOK7 isoform 1 plays an inhibitory role on the proliferation and migration of lung cancer cells.
Title: The downstream of tyrosine kinase 7 is reduced in lung cancer and is associated with poor survival of patients with lung cancer.
Individuals with DOK7 congenital myasthenic syndrome displayed stridor and feeding difficulties at birth or progressive weakness despite normal milestones in infancy pointing to a diagnosis and should lead to neurophysiological and genetic investigation
Title: DOK7 congenital myasthenic syndrome in childhood: early diagnostic clues in 23 children.
this study demonistrated that Salbutamol is an effective treatment in patient wity congenital myasthenic syndrome due to DOK7 mutation.
Title: Salbutamol therapy in congenital myasthenic syndrome due to DOK7 mutation.
DOK7 limb-girdle myasthenic syndrome can mimick congenital muscular dystrophy.
Title: DOK7 limb-girdle myasthenic syndrome mimicking congenital muscular dystrophy.
Hypermethylation of DOK7 occurs years before tumor diagnosis, suggesting a role as a powerful epigenetic blood-based biomarker as well as providing insights into breast cancer pathogenesis
Title: DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker.
In contrast to AChR deficiency due to epsilon subunit mutations, onset of DOK7 CMS tends to be later--ages two to three years--and in DOK7 CMS eye movements are usually spared and anticholinesterases can exacerbate the weakness
Title: DOK7 congenital myasthenic syndrome.
The DOK7 gene is highly polymorphic, and within these many variants, a spectrum of mutations that can underlie DOK7 Congenital myasthenic syndromes that will inform in managing this disorder, were defined.
Title: The spectrum of mutations that underlie the neuromuscular junction synaptopathy in DOK7 congenital myasthenic syndrome.
Sequencing of DOK-7 in seronegative myasthenia gravis patients reveals no mutations.
Title: Investigation for RAPSN and DOK-7 mutations in a cohort of seronegative myasthenia gravis patients.
6 CMS patients with DOK7 mutations had congenital stridor, bilateral vocal cord palsy and difficulty with feeding
Title: Congenital stridor with feeding difficulty as a presenting symptom of Dok7 congenital myasthenic syndrome.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Myasthenia, limb-girdle, familial MedGen: C1850792 OMIM: 254300 GeneReviews: Congenital Myasthenic Syndromes	Compare labs
Pena-Shokeir syndrome type I MedGen: C1276035 OMIM: 208150 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
Discovery and refinement of loci associated with lipid levels. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

Homologs of the DOK7 gene: The DOK7 gene is conserved in chimpanzee, dog, cow, mouse, and rat.
Orthologs from Annotation Pipeline: 214 organisms have orthologs with human gene DOK7
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
lipid binding	IEA Inferred from Electronic Annotation more info
protein kinase binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
positive regulation of protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
cell junction	IEA Inferred from Electronic Annotation more info
mitochondrion	IDA Inferred from Direct Assay more info
nucleoplasm	IDA Inferred from Direct Assay more info
nucleus	IDA Inferred from Direct Assay more info
plasma membrane	IEA Inferred from Electronic Annotation more info
synapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: protein Dok-7

Names: downstream of tyrosine kinase 7

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013072.2 RefSeqGene

Range

5001..36177

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001164673.1 → NP_001158145.1 protein Dok-7 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 3' UTR and coding sequence and uses an alternate splice site in the central coding region compared to variant 4, that causes a frameshift. The encoded isoform (2) differs in the central region and has a shorter and distinct C-terminus compared to isoform 4.

Source sequence(s)

AK091037, BM684814, DA205628

Consensus CDS

CCDS54717.1

UniProtKB/Swiss-Prot

Q18PE1

Related

ENSP00000423614.1, OTTHUMP00000216837, ENST00000507039.5, OTTHUMT00000242849

Conserved Domains (3) summary

cd14677
Location:6 → 107

PH_DOK7; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 7

pfam00169
Location:8 → 108

PH; PH domain

cl17171
Location:108 → 174

PH-like; Pleckstrin homology-like domain
NM_001256896.1 → NP_001243825.1 protein Dok-7 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate internal promoter and differs in the 3' UTR and coding sequence compared to variant 4. The encoded isoform (3) is significantly shorter at the N-terminus and has a shorter and distinct C-terminus compared to isoform 4.

Source sequence(s)

AK091037, AK096456, BM684814, DA823926

Consensus CDS

CCDS87206.1

UniProtKB/Swiss-Prot

Q18PE1

UniProtKB/TrEMBL

A0A1W2PRA3, Q8N1M3

Related

ENSP00000492194.1, ENST00000515886.5
NM_001301071.1 → NP_001288000.1 protein Dok-7 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) encodes the longest isoform (4).

Source sequence(s)

AK075037, AL590235, BC141852, DA205628

UniProtKB/Swiss-Prot

Q18PE1

Conserved Domains (2) summary

cd13165
Location:108 → 208

PTB_DOK7; Downstream of tyrosine kinase 7 phosphotyrosine-binding domain (PTBi)

cd14677
Location:6 → 107

PH_DOK7; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 7
NM_001363811.1 → NP_001350740.1 protein Dok-7 isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks two alternate exons compared to variant 4. The resulting isoform (5) has the same N- and C-termini but is shorter compared to isoform 4.

Source sequence(s)

AL590235

Consensus CDS

CCDS87205.1

Conserved Domains (1) summary

cl17171
Location:6 → 33

PH-like; Pleckstrin homology-like domain
NM_173660.4 → NP_775931.3 protein Dok-7 isoform 1

See identical proteins and their annotated locations for NP_775931.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) differs in the 3' UTR and coding sequence compared to variant 4. The resulting isoform (1) has a shorter and distinct C-terminus compared to isoform 4.

Source sequence(s)

AK091037, BC141852, BM684814, DA205628

Consensus CDS

CCDS3370.2

UniProtKB/Swiss-Prot

Q18PE1

Related

ENSP00000344432.5, OTTHUMP00000194785, ENST00000340083.5, OTTHUMT00000313538

Conserved Domains (2) summary

cd13165
Location:108 → 208

PTB_DOK7; Downstream of tyrosine kinase 7 phosphotyrosine-binding domain (PTBi)

cd14677
Location:6 → 107

PH_DOK7; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 7

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p12 Primary Assembly

Range

3463306..3501476

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011513435.2 → XP_011511737.1 protein Dok-7 isoform X1

Conserved Domains (2) summary

cd13165
Location:108 → 208

PTB_DOK7; Downstream of tyrosine kinase 7 phosphotyrosine-binding domain (PTBi)

cd14677
Location:6 → 107

PH_DOK7; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 7
XM_011513437.2 → XP_011511739.1 protein Dok-7 isoform X2

Conserved Domains (1) summary

cl17171
Location:36 → 70

PH-like; Pleckstrin homology-like domain
XM_017008038.1 → XP_016863527.1 protein Dok-7 isoform X3

Related

ENSP00000495701.1, ENST00000643608.1

Conserved Domains (1) summary

cl17171
Location:6 → 33

PH-like; Pleckstrin homology-like domain