GAK

cyclin G associated kinase, the group of C2 tensin-type domain containing|DNAJ (HSP40) heat shock proteins

Basic information

Region (hg38): 4:849275-932373

Links

ENSG00000178950 ∙ NCBI:2580 ∙ OMIM:602052 ∙ HGNC:4113 ∙ Uniprot:O14976 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Inborn genetic diseases (69 variants)
• not provided (16 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GAK gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	4	9
missense			67	3	6	76
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	67	8	10

Variants in GAK

This is a list of pathogenic ClinVar variants found in the GAK region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-849689-G-A		not specified	Uncertain significance (May 17, 2023)
4-849690-A-G		not specified	Uncertain significance (May 17, 2023)
4-849710-G-A			Likely benign (Apr 25, 2018)
4-849718-G-A			Benign (Jul 06, 2018)
4-849723-T-G		not specified	Uncertain significance (Mar 13, 2023)
4-849748-G-A			Benign (Jun 20, 2018)
4-849758-T-C		not specified	Uncertain significance (Nov 15, 2021)
4-849761-G-A		not specified	Uncertain significance (Jul 13, 2021)
4-849920-C-T		not specified	Uncertain significance (Jan 02, 2024)
4-849932-T-C			Benign (Feb 24, 2021)
4-849947-G-A		not specified	Uncertain significance (Dec 21, 2023)
4-849961-G-A			Likely benign (Jan 01, 2023)
4-849977-G-A		not specified	Uncertain significance (Nov 09, 2021)
4-849996-C-T		not specified	Uncertain significance (Feb 03, 2022)
4-850007-G-A		not specified	Uncertain significance (Apr 28, 2023)
4-850940-A-C			Benign (Mar 29, 2018)
4-850955-G-A		not specified	Uncertain significance (Jul 12, 2022)
4-851015-G-C		not specified	Uncertain significance (Jun 29, 2023)
4-851786-C-T		not specified	Uncertain significance (Oct 13, 2023)
4-851789-C-T		not specified	Uncertain significance (Sep 01, 2021)
4-851809-G-A		not specified	Uncertain significance (Jan 09, 2024)
4-851812-T-C		not specified	Uncertain significance (Nov 09, 2021)
4-851842-G-C			Benign (Dec 31, 2019)
4-851849-G-C		not specified	Uncertain significance (Feb 23, 2023)
4-851860-G-A		not specified	Uncertain significance (Dec 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GAK	protein_coding	protein_coding	ENST00000314167	28	83098

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00518	0.995	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0210	816	818	0.998	0.0000530	8474
Missense in Polyphen		211	281.48	0.74961		2985
Synonymous	-2.90	443	372	1.19	0.0000283	2649
Loss of Function	5.33	17	62.5	0.272	0.00000305	712

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000149	0.000149
Ashkenazi Jewish	0.000104	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000163	0.000158
Middle Eastern	0.000109	0.000109
South Asian	0.000174	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Associates with cyclin G and CDK5. Seems to act as an auxilin homolog that is involved in the uncoating of clathrin- coated vesicles by Hsc70 in non-neuronal cells. Expression oscillates slightly during the cell cycle, peaking at G1. {ECO:0000269|PubMed:10625686}.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Golgi Associated Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking;Clathrin-mediated endocytosis (Consensus)

Recessive Scores

• pRec: 0.215

Intolerance Scores

• loftool: 0.165
• rvis_EVS: -1.35
• rvis_percentile_EVS: 4.59

Haploinsufficiency Scores

• pHI: 0.229
• hipred: Y
• hipred_score: 0.614
• ghis: 0.528

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.971

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gak
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; normal 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)

Zebrafish Information Network

• Gene name: gak
• Affected structure: tectal ventricle
• Phenotype tag: abnormal
• Phenotype quality: increased size

Gene ontology

• Biological process: protein phosphorylation;receptor-mediated endocytosis;endoplasmic reticulum organization;Golgi organization;cell cycle;negative regulation of neuron projection development;synaptic vesicle uncoating;protein localization to Golgi apparatus;chaperone cofactor-dependent protein refolding;membrane organization;clathrin coat disassembly;clathrin-dependent endocytosis;protein localization to plasma membrane;Golgi to lysosome transport;clathrin-coated pit assembly
• Cellular component: cytoplasm;Golgi apparatus;cytosol;focal adhesion;membrane;vesicle;intracellular membrane-bounded organelle;perinuclear region of cytoplasm;presynapse
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;clathrin binding;cyclin binding;chaperone binding