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.

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.

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				1	1	2
missense			32		1	33
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	32	1	2

Variants in AAK1

This is a list of pathogenic ClinVar variants found in the AAK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-69478983-G-A		not specified	Uncertain significance (Jun 06, 2023)
2-69479025-G-C		not specified	Uncertain significance (Jun 18, 2021)
2-69479028-C-T		not specified	Uncertain significance (Aug 12, 2021)
2-69479040-G-T		Tooth agenesis	Uncertain significance (-)
2-69480916-G-T		not specified	Uncertain significance (Jan 05, 2022)
2-69480947-C-G		not specified	Uncertain significance (Dec 02, 2022)
2-69495988-G-A		not specified	Uncertain significance (Sep 16, 2021)
2-69496027-C-T		not specified	Uncertain significance (Mar 29, 2022)
2-69496044-C-T		not specified	Uncertain significance (May 06, 2024)
2-69505662-C-T		not specified	Uncertain significance (Jul 19, 2023)
2-69507428-A-C			Benign (May 21, 2018)
2-69507504-G-A			Benign (Jul 16, 2018)
2-69507529-C-T		not specified	Uncertain significance (Mar 11, 2022)
2-69507535-G-T		not specified	Uncertain significance (Aug 21, 2023)
2-69509300-C-T		not specified	Uncertain significance (Dec 09, 2023)
2-69509339-C-T		not specified	Uncertain significance (Aug 19, 2021)
2-69509382-G-C		not specified	Uncertain significance (Feb 27, 2024)
2-69514484-G-A		not specified	Uncertain significance (Dec 03, 2021)
2-69514494-G-A		not specified	Uncertain significance (Jun 30, 2022)
2-69514736-T-G		not specified	Uncertain significance (Jun 02, 2024)
2-69518970-T-G		not specified	Uncertain significance (Dec 17, 2023)
2-69518997-G-A		not specified	Uncertain significance (Feb 03, 2022)
2-69519033-T-A		not specified	Uncertain significance (Feb 10, 2022)
2-69519087-G-A		not specified	Uncertain significance (Jun 11, 2021)
2-69519088-C-A		not specified	Uncertain significance (Mar 18, 2024)

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

• 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