AKAP9

A-kinase anchoring protein 9, the group of A-kinase anchoring proteins|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 7:91940840-92110673

Links

ENSG00000127914 ∙ NCBI:10142 ∙ OMIM:604001 ∙ HGNC:379 ∙ Uniprot:Q99996 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• long QT syndrome 11 (Limited), mode of inheritance: AD
• long QT syndrome (Disputed Evidence), mode of inheritance: AD
• long QT syndrome 11 (Limited), mode of inheritance: AD
• male infertility with azoospermia or oligozoospermia due to single gene mutation (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Long QT syndrome 11	AD	Cardiovascular	In order to prevent sequelae including syncope, cardiac arrest and sudden death prophylactic use of beta blockers in asymptomatic individuals may be beneficial; ICD may be indicated for individuals refractory to beta-blocker treatment or with history of cardiac arrest; Agents that can contribute to prolonged QT or related dysrhythmias should be avoided, as should activities associated with high stress/intense exertion	Cardiovascular	10220144; 18093912; 20809527; 21430528; 20301308

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AKAP9 gene.

• Long_QT_syndrome (2203 variants)
• Cardiovascular_phenotype (2198 variants)
• not_provided (337 variants)
• Long_QT_syndrome_11 (272 variants)
• not_specified (183 variants)
• Congenital_long_QT_syndrome (82 variants)
• AKAP9-related_disorder (66 variants)
• Cardiomyopathy (11 variants)
• Long_QT_syndrome_1 (6 variants)
• Primary_dilated_cardiomyopathy (4 variants)
• Cardiac_arrest (4 variants)
• Hypertrophic_cardiomyopathy (4 variants)
• Ventricular_fibrillation (4 variants)
• Cardiac_arrhythmia (2 variants)
• Wolff-Parkinson-White_pattern (2 variants)
• Heart_failure (2 variants)
• Ventricular_tachycardia (2 variants)
• Restrictive_cardiomyopathy (1 variants)
• Sudden_cardiac_death (1 variants)
• Brugada_syndrome_1 (1 variants)
• Brugada_syndrome (1 variants)
• Arrhythmogenic_right_ventricular_cardiomyopathy (1 variants)
• Atrial_fibrillation (1 variants)
• Long_QT_syndrome_2 (1 variants)
• Catecholaminergic_polymorphic_ventricular_tachycardia (1 variants)
• unspecified_heart_condition (1 variants)
• Amyloidosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AKAP9 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005751.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			20	744	5	769
missense		2	1749	389	5	2145
nonsense		3	54			57
start loss			1			1
frameshift			73	1	3	77
splice donor/acceptor (+/-2bp)			41			41
Total	0	5	1938	1134	13

Highest pathogenic variant AF is 0.0000047886692

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AKAP9	protein_coding	protein_coding	ENST00000356239	50	169807

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125545	0	203	125748	0.000807

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.128	1850	1.83e+3	1.01	0.0000895	25902
Missense in Polyphen		588	654.49	0.89841		9778
Synonymous	0.762	625	650	0.962	0.0000317	6822
Loss of Function	9.06	71	214	0.332	0.0000115	2680

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00138	0.00137
Ashkenazi Jewish	0.000212	0.000198
East Asian	0.000492	0.000489
Finnish	0.00122	0.00120
European (Non-Finnish)	0.000959	0.000950
Middle Eastern	0.000492	0.000489
South Asian	0.000732	0.000719
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Scaffolding protein that assembles several protein kinases and phosphatases on the centrosome and Golgi apparatus. Required to maintain the integrity of the Golgi apparatus (PubMed:10202149, PubMed:15047863). Required for microtubule nucleation at the cis-side of the Golgi apparatus (PubMed:15047863, PubMed:19242490). Required for association of the centrosomes with the poles of the bipolar mitotic spindle during metaphase (PubMed:25657325). In complex with PDE4DIP isoform 13/MMG8/SMYLE, recruits CAMSAP2 to the Golgi apparatus and tethers non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:27666745, PubMed:28814570). In complex with PDE4DIP isoform 13/MMG8/SMYLE, EB1/MAPRE1 and CDK5RAP2, contributes to microtubules nucleation and extension also from the centrosome to the cell periphery (PubMed:29162697). {ECO:0000269|PubMed:10202149, ECO:0000269|PubMed:15047863, ECO:0000269|PubMed:19242490, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:27666745, ECO:0000269|PubMed:28814570, ECO:0000269|PubMed:29162697}.
• Disease: DISEASE: Long QT syndrome 11 (LQT11) [MIM:611820]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. {ECO:0000269|PubMed:18093912}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: G Protein Signaling Pathways;NO-cGMP-PKG mediated Neuroprotection;Disease;Signal Transduction;protein kinase a at the centrosome;Neuronal System;Phase 2 - plateau phase;Phase 3 - rapid repolarisation;Cardiac conduction;Muscle contraction;Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;G2/M Transition;Mitotic G2-G2/M phases;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;M Phase;Ras activation upon Ca2+ influx through NMDA receptor;CREB phosphorylation through the activation of Ras;Unblocking of NMDA receptor, glutamate binding and activation;CREB phosphorylation through the activation of CaMKII;Post NMDA receptor activation events;Activation of NMDA receptor and postsynaptic events;Cell Cycle;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.933
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.45

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.444

Gene Damage Prediction

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

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;microtubule nucleation;signal transduction;negative regulation of adenylate cyclase activity;chemical synaptic transmission;regulation of G2/M transition of mitotic cell cycle;positive regulation of microtubule polymerization;positive regulation of peptidyl-serine phosphorylation;response to electrical stimulus;maintenance of centrosome location;regulation of membrane repolarization;regulation of ventricular cardiac muscle cell membrane repolarization;cellular response to cAMP;regulation of heart rate by cardiac conduction;ciliary basal body-plasma membrane docking;regulation of cardiac muscle cell action potential involved in regulation of contraction;regulation of postsynaptic neurotransmitter receptor activity;positive regulation of potassium ion transmembrane transporter activity;regulation of Golgi organization
• Cellular component: Golgi apparatus;Golgi stack;cis-Golgi network;centrosome;cytosol;cytoskeleton;voltage-gated potassium channel complex;neuronal cell body;intracellular membrane-bounded organelle;dendritic branch;synaptic membrane;glutamatergic synapse;extrinsic component of postsynaptic density membrane
• Molecular function: DNA binding;signaling receptor binding;protein binding;potassium channel regulator activity;protein-containing complex scaffold activity;protein kinase A regulatory subunit binding;ion channel binding