DOK7

docking protein 7

Basic information

Region (hg38): 4:3463306-3501473

Previous symbols: [ "C4orf25" ]

Links

ENSG00000175920

∙ NCBI:285489 ∙ OMIM:610285 ∙ HGNC:26594 ∙ Uniprot:Q18PE1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

congenital myasthenic syndrome 10 (Strong), mode of inheritance: AR
congenital myasthenic syndrome 10 (Strong), mode of inheritance: AR
fetal akinesia deformation sequence 3 (Limited), mode of inheritance: AR
congenital myasthenic syndrome 10 (Definitive), mode of inheritance: AR
fetal akinesia deformation sequence 1 (Supportive), mode of inheritance: AR
postsynaptic congenital myasthenic syndrome (Supportive), mode of inheritance: AR
congenital myasthenic syndrome 10 (Strong), mode of inheritance: AR
fetal akinesia deformation sequence 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital, 10	AR	Musculoskeletal; Neurologic; Pharmacogenomic	Unlike individuals with other types of genetic myasthenia, individuals with relevant DOK7 variants typically do not respond to chronic AChE inhibitor treatment, but other therapies (eg, albuterol, ephedrine, salbutamol) have been reported to result in marked clinical improvement; Agents that affect neuromuscular transmission and exacerbate myasthenic manifestations should be avoided; Additional neurologic monitoring in pregnancy may be beneficial	Musculoskeletal; Neurologic	16917026; 18626973; 18707767; 19261599; 19837590; 20012313; 20301347; 20458068; 20554332; 20562457; 20610155; 22661499; 22884442; 22911480; 23108489; 23219351; 23657916; 23790237; 23831158
Fetal akinesia deformation sequence 3 likely represents an extreme phenotype of Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DOK7 gene.

Congenital_myasthenic_syndrome_10 (1003 variants)
Fetal_akinesia_deformation_sequence_1 (987 variants)
not_provided (243 variants)
Inborn_genetic_diseases (166 variants)
Fetal_akinesia_deformation_sequence_3 (92 variants)
not_specified (58 variants)
DOK7-related_disorder (33 variants)
Congenital_myasthenic_syndrome (18 variants)
Ritscher-Schinzel_syndrome_2 (3 variants)
See_cases (3 variants)
Abnormality_of_the_musculature (1 variants)
Rett_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DOK7 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000173660.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		2 clinvar	3 clinvar	319 clinvar	6 clinvar	330
missense	4 clinvar	13 clinvar	358 clinvar	44 clinvar	6 clinvar	425
nonsense	14 clinvar	18 clinvar	1 clinvar			33
start loss			1			1
frameshift	38 clinvar	36 clinvar	2 clinvar	1 clinvar		77
splice donor/acceptor (+/-2bp)	6 clinvar	16 clinvar	4 clinvar			26
Total	62	85	369	364	12

Highest pathogenic variant AF is 0.001114792

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DOK7	protein_coding	protein_coding	ENST00000340083	7	38168

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000103	0.949	125559	0	48	125607	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.55	448	320	1.40	0.0000213	3103
Missense in Polyphen		155	124.48	1.2452		1164
Synonymous	-4.35	228	158	1.44	0.0000118	1121
Loss of Function	1.77	9	16.8	0.535	7.70e-7	190

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000585	0.000556
Ashkenazi Jewish	0.00	0.00
East Asian	0.000170	0.000163
Finnish	0.000131	0.0000924
European (Non-Finnish)	0.000232	0.000203
Middle Eastern	0.000170	0.000163
South Asian	0.000235	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Probable muscle-intrinsic activator of MUSK that plays an essential role in neuromuscular synaptogenesis. Acts in aneural activation of MUSK and subsequent acetylcholine receptor (AchR) clustering in myotubes. Induces autophosphorylation of MUSK. {ECO:0000269|PubMed:20603078}.;
Disease: DISEASE: Myasthenic syndrome, congenital, 10 (CMS10) [MIM:254300]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS10 is an autosomal recessive, post-synaptic form characterized by a typical 'limb girdle' pattern of muscle weakness with small, simplified neuromuscular junctions but normal acetylcholine receptor and acetylcholinesterase function. {ECO:0000269|PubMed:16917026, ECO:0000269|PubMed:17439981, ECO:0000269|PubMed:20012313, ECO:0000269|PubMed:20603078, ECO:0000269|PubMed:22661499}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Haploinsufficiency Scores

pHI: 0.171
hipred: N
hipred_score: 0.342
ghis: 0.433

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.319

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Dok7
Phenotype: growth/size/body region phenotype; muscle phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype;

Zebrafish Information Network

Gene name: dok7
Affected structure: slow muscle cell
Phenotype tag: abnormal
Phenotype quality: curved

Gene ontology

Biological process: positive regulation of protein tyrosine kinase activity
Cellular component: nucleus;nucleoplasm;mitochondrion;plasma membrane;cell junction;synapse
Molecular function: lipid binding;protein kinase binding