AKAP8

A-kinase anchoring protein 8, the group of A-kinase anchoring proteins

Basic information

Region (hg38): 19:15353385-15379815

Links

ENSG00000105127 ∙ NCBI:10270 ∙ OMIM:604692 ∙ HGNC:378 ∙ Uniprot:O43823 ∙ 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 AKAP8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AKAP8 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				6	8	14
missense			57	13	5	75
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	2	3
non coding						0
Total	0	0	57	19	13

Variants in AKAP8

This is a list of pathogenic ClinVar variants found in the AKAP8 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-15354933-G-A			Likely benign (Oct 01, 2022)
19-15354974-C-T		not specified	Likely benign (Aug 02, 2022)
19-15354997-C-T		not specified	Uncertain significance (Jul 28, 2021)
19-15355034-C-T		not specified	Uncertain significance (May 20, 2024)
19-15355079-C-T		not specified	Uncertain significance (Aug 14, 2023)
19-15355088-C-T		not specified	Uncertain significance (Feb 12, 2024)
19-15355096-G-A		not specified	Uncertain significance (Jul 19, 2023)
19-15355148-C-T		not specified	Likely benign (Mar 19, 2024)
19-15355149-G-A			Benign (Dec 31, 2019)
19-15355165-G-A		not specified	Likely benign (Mar 29, 2022)
19-15355169-G-A		not specified	Uncertain significance (Apr 17, 2024)
19-15355183-G-T		not specified	Uncertain significance (Mar 11, 2024)
19-15355193-C-T		not specified	Uncertain significance (Aug 02, 2022)
19-15355229-C-T		not specified	Uncertain significance (Jul 19, 2022)
19-15355243-G-T		not specified	Uncertain significance (Sep 28, 2022)
19-15355289-T-G		not specified	Uncertain significance (Jun 18, 2021)
19-15359011-A-C		not specified	Uncertain significance (Dec 28, 2022)
19-15359053-C-G		not specified	Uncertain significance (Dec 27, 2023)
19-15360871-C-T		not specified	Uncertain significance (Dec 01, 2022)
19-15360872-G-A			Likely benign (Apr 01, 2022)
19-15360903-T-C		not specified	Uncertain significance (May 02, 2024)
19-15360947-G-T			Likely benign (Jul 20, 2018)
19-15360978-C-T		not specified	Uncertain significance (Oct 20, 2021)
19-15361743-G-A		not specified	Uncertain significance (Jan 06, 2023)
19-15361750-G-T			Likely benign (Dec 05, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AKAP8	protein_coding	protein_coding	ENST00000269701	14	26414

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.664	0.336	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0000295	453	453	1.00	0.0000303	4557
Missense in Polyphen		130	145.81	0.89158		1518
Synonymous	-1.29	211	188	1.12	0.0000147	1314
Loss of Function	4.04	6	29.8	0.201	0.00000135	338

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000163	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.000231	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000267	0.0000264
Middle Eastern	0.000231	0.000217
South Asian	0.0000327	0.0000327
Other	0.000173	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Anchoring protein that mediates the subcellular compartmentation of cAMP-dependent protein kinase (PKA type II) (PubMed:9473338). Acts as an anchor for a PKA-signaling complex onto mitotic chromosomes, which is required for maintenance of chromosomes in a condensed form throughout mitosis. Recruits condensin complex subunit NCAPD2 to chromosomes required for chromatin condensation; the function appears to be independent from PKA-anchoring (PubMed:10601332, PubMed:10791967, PubMed:11964380). May help to deliver cyclin D/E to CDK4 to facilitate cell cycle progression (PubMed:14641107). Required for cell cycle G2/M transition and histone deacetylation during mitosis. In mitotic cells recruits HDAC3 to the vicinity of chromatin leading to deacetylation and subsequent phosphorylation at 'Ser-10' of histone H3; in this function may act redundantly with AKAP8L (PubMed:16980585). Involved in nuclear retention of RPS6KA1 upon ERK activation thus inducing cell proliferation (PubMed:22130794). May be involved in regulation of DNA replication by acting as scaffold for MCM2 (PubMed:12740381). Enhances HMT activity of the KMT2 family MLL4/WBP7 complex and is involved in transcriptional regulation. In a teratocarcinoma cell line is involved in retinoic acid-mediated induction of developmental genes implicating H3 'Lys-4' methylation (PubMed:23995757). May be involved in recruitment of active CASP3 to the nucleus in apoptotic cells (PubMed:16227597). May act as a carrier protein of GJA1 for its transport to the nucleus (PubMed:26880274). Seems to involved in modulation of rDNA transcription. Preferentially binds GC-rich DNA in vitro and associates to GC-rich ribosomal RNA promoters (PubMed:26683827). Involved in modulation of Toll-like receptor signaling. Required for the cAMP-dependent suppression of TNF-alpha in early stages of LPS-induced macrophage activation; the function probably implicates targeting of PKA to NFKB1 (By similarity). {ECO:0000250|UniProtKB:Q63014, ECO:0000250|UniProtKB:Q9DBR0, ECO:0000269|PubMed:10601332, ECO:0000269|PubMed:10791967, ECO:0000269|PubMed:11964380, ECO:0000269|PubMed:16980585, ECO:0000269|PubMed:22130794, ECO:0000269|PubMed:26683827, ECO:0000269|PubMed:26880274, ECO:0000305|PubMed:14641107, ECO:0000305|PubMed:9473338}.
• Pathway: miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in squamous cell - TarBase;G Protein Signaling Pathways;akap95 role in mitosis and chromosome dynamics;TNFalpha (Consensus)

Recessive Scores

• pRec: 0.271

Intolerance Scores

• loftool: 0.583
• rvis_EVS: 0.5
• rvis_percentile_EVS: 79.66

Haploinsufficiency Scores

• pHI: 0.111
• hipred: Y
• hipred_score: 0.658
• ghis: 0.512

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.962

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Akap8
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; digestive/alimentary phenotype; respiratory system 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); normal phenotype

Gene ontology

• Biological process: mitotic cell cycle;mitotic chromosome condensation;signal transduction;protein transport;positive regulation of histone deacetylation;negative regulation of tumor necrosis factor production;regulation of histone phosphorylation;cell cycle G2/M phase transition;innate immune response;cellular response to lipopolysaccharide;cellular response to prostaglandin E stimulus
• Cellular component: condensed chromosome;female pronucleus;nucleus;nucleoplasm;nucleolus;mitochondrion;Golgi apparatus;membrane;nuclear matrix
• Molecular function: double-stranded DNA binding;RNA binding;protein binding;zinc ion binding;protein kinase A regulatory subunit binding;histone deacetylase binding;NF-kappaB binding