AAK1

AP2 associated kinase 1, the group of Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): 2:69457997-69674349

Links

ENSG00000115977

∙ NCBI:22848 ∙ OMIM:616405 ∙ HGNC:19679 ∙ Uniprot:Q2M2I8 ∙ 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 AAK1 gene.

not_specified (82 variants)
not_provided (4 variants)
Tooth_agenesis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AAK1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014911.5. 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				3 clinvar	1 clinvar	4
missense			81 clinvar	1 clinvar	1 clinvar	83
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	81	4	2

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AAK1	protein_coding	protein_coding	ENST00000409085	21	212950

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.05e-7	124639	0	6	124645	0.0000241

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.61	342	508	0.674	0.0000258	6227
Missense in Polyphen		62	100.55	0.61662		1265
Synonymous	0.334	189	195	0.970	0.0000103	1934
Loss of Function	6.20	2	48.7	0.0411	0.00000224	544

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000292	0.0000292
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000466	0.0000464
European (Non-Finnish)	0.0000366	0.0000354
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis. Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1. Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes. Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes. Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity. {ECO:0000269|PubMed:12952931, ECO:0000269|PubMed:17494869, ECO:0000269|PubMed:18657069, ECO:0000269|PubMed:21464124}.;
Pathway: Vesicle-mediated transport;Membrane Trafficking;Clathrin-mediated endocytosis;Cargo recognition for clathrin-mediated endocytosis (Consensus)

Recessive Scores

pRec: 0.0954

Intolerance Scores

loftool
rvis_EVS: -0.66
rvis_percentile_EVS: 15.91

Haploinsufficiency Scores

pHI: 0.0991
hipred: Y
hipred_score: 0.710
ghis: 0.541

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.446

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Aak1
Phenotype: hearing/vestibular/ear phenotype;

Gene ontology

Biological process: protein phosphorylation;endocytosis;regulation of endocytosis;regulation of protein localization;positive regulation of Notch signaling pathway;protein autophosphorylation;protein stabilization;membrane organization;regulation of clathrin-dependent endocytosis
Cellular component: nucleus;cytosol;clathrin-coated pit;extrinsic component of plasma membrane;clathrin-coated vesicle;cell leading edge;terminal bouton
Molecular function: protein serine/threonine kinase activity;Notch binding;protein binding;ATP binding;AP-2 adaptor complex binding