GAK

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

Basic information

Region (hg38): 4:849276-932373

Links

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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 101.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_005255.4	NP_005246.2	28	yes	-
ENST00000314167.9	ENSP00000314499.4	28	yes	-
NM_001318134.2	NP_001305063.1	25	-	-
ENST00000510799.1	ENSP00000426062.1	5	-	-

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• not_specified (245 variants)
• not_provided (15 variants)
• Incidental_Discovery (1 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. These statistics are base on transcript: NM_005255.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	9	4	16
missense			239	12	4	255
nonsense			1			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9			9
Total	0	0	252	21	8

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
		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

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

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