AKAP13

A-kinase anchoring protein 13, the group of Dbl family Rho GEFs|A-kinase anchoring proteins|Pleckstrin homology domain containing|MicroRNA protein coding host genes|Minor histocompatibility antigens

Basic information

Region (hg38): 15:85380570-85749358

Previous symbols: [ "LBC" ]

Links

ENSG00000170776 ∙ NCBI:11214 ∙ OMIM:604686 ∙ HGNC:371 ∙ Uniprot:Q12802 ∙ 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 AKAP13 gene.

• Inborn genetic diseases (118 variants)
• not provided (27 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AKAP13 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				8	9	17
missense			111	12	5	128
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	111	20	14

Variants in AKAP13

This is a list of pathogenic ClinVar variants found in the AKAP13 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-85521464-G-C		not specified	Uncertain significance (Nov 21, 2022)
15-85521518-C-T		not specified	Uncertain significance (Apr 12, 2022)
15-85533620-G-A		not specified	Uncertain significance (Jun 29, 2022)
15-85533623-C-G		not specified	Uncertain significance (Jan 04, 2024)
15-85533860-G-A		not specified	Uncertain significance (Feb 02, 2022)
15-85533870-G-C		not specified	Uncertain significance (Aug 17, 2022)
15-85543784-G-A		not specified	Uncertain significance (Nov 15, 2021)
15-85543808-T-C		not specified	Uncertain significance (Sep 27, 2021)
15-85543845-G-T		not specified	Uncertain significance (Oct 25, 2023)
15-85543853-C-A		not specified	Uncertain significance (Oct 27, 2023)
15-85543881-C-G		not specified	Uncertain significance (Aug 28, 2023)
15-85543936-C-G		not specified	Uncertain significance (Aug 01, 2022)
15-85575172-A-G		not specified	Uncertain significance (Jul 09, 2021)
15-85575184-A-C		not specified	Uncertain significance (Jul 20, 2022)
15-85575219-G-A		not specified	Uncertain significance (Mar 07, 2024)
15-85575226-A-C		not specified	Uncertain significance (Nov 10, 2022)
15-85575238-C-G		not specified	Uncertain significance (May 31, 2022)
15-85575283-G-A		not specified	Uncertain significance (Oct 13, 2023)
15-85575286-C-G		not specified	Uncertain significance (Nov 02, 2023)
15-85575319-A-C		not specified	Uncertain significance (Oct 14, 2023)
15-85578982-A-G		not specified	Uncertain significance (Dec 03, 2021)
15-85579068-G-A			Benign (Apr 30, 2018)
15-85579081-G-C		not specified	Uncertain significance (Oct 06, 2021)
15-85579201-G-A		not specified	Uncertain significance (Dec 17, 2023)
15-85579216-T-C		not specified	Likely benign (Nov 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AKAP13	protein_coding	protein_coding	ENST00000361243	36	368785

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.929	0.0709	125640	0	108	125748	0.000430

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.64	1700	1.52e+3	1.12	0.0000823	18512
Missense in Polyphen		430	448.95	0.95779		5611
Synonymous	-3.54	677	570	1.19	0.0000318	5516
Loss of Function	7.97	25	119	0.211	0.00000643	1466

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00280	0.00280
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000927	0.0000924
European (Non-Finnish)	0.000379	0.000378
Middle Eastern	0.000218	0.000217
South Asian	0.000165	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. Activates RHOA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor (PubMed:11546812, PubMed:15229649, PubMed:23090968, PubMed:25186459, PubMed:24993829). May also activate other Rho family members (PubMed:11546812). Part of a kinase signaling complex that links ADRA1A and ADRA1B adrenergic receptor signaling to the activation of downstream p38 MAP kinases, such as MAPK11 and MAPK14 (PubMed:17537920, PubMed:23716597, PubMed:21224381). Part of a signaling complex that links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional activity (PubMed:23090968). Part of a RHOA-dependent signaling cascade that mediates responses to lysophosphatidic acid (LPA), a signaling molecule that activates G-protein coupled receptors and potentiates transcriptional activation of the glucocorticoid receptor NR3C1 (PubMed:16469733). Part of a signaling cascade that stimulates MEF2C-dependent gene expression in response to lysophosphatidic acid (LPA) (By similarity). Part of a signaling pathway that activates MAPK11 and/or MAPK14 and leads to increased transcription activation of the estrogen receptors ESR1 and ESR2 (PubMed:9627117, PubMed:11579095). Part of a signaling cascade that links cAMP and EGFR signaling to BRAF signaling and to PKA- mediated phosphorylation of KSR1, leading to the activation of downstream MAP kinases, such as MAPK1 or MAPK3 (PubMed:21102438). Functions as scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1. This promotes activation of PRKD1, leading to increased phosphorylation of HDAC5 and ultimately cardiomyocyte hypertrophy (By similarity). Has no guanine nucleotide exchange activity on CDC42, Ras or Rac (PubMed:11546812). Required for normal embryonic heart development, and in particular for normal sarcomere formation in the developing cardiomyocytes (By similarity). Plays a role in cardiomyocyte growth and cardiac hypertrophy in response to activation of the beta-adrenergic receptor by phenylephrine or isoproterenol (PubMed:17537920, PubMed:23090968). Required for normal adaptive cardiac hypertrophy in response to pressure overload (PubMed:23716597). Plays a role in osteogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q394, ECO:0000269|PubMed:11546812, ECO:0000269|PubMed:11579095, ECO:0000269|PubMed:17537920, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:23716597, ECO:0000269|PubMed:24993829, ECO:0000269|PubMed:25186459, ECO:0000269|PubMed:9627117, ECO:0000269|PubMed:9891067}.
• Pathway: Glucocorticoid Receptor Pathway;Nuclear Receptors Meta-Pathway;G Protein Signaling Pathways;Signaling by GPCR;Signal Transduction;rho-selective guanine exchange factor akap13 mediates stress fiber formation;Rho GTPase cycle;Signaling by Rho GTPases;NRAGE signals death through JNK;Death Receptor Signalling;p75 NTR receptor-mediated signalling;G alpha (12/13) signalling events;GPCR downstream signalling;PAR1-mediated thrombin signaling events;Cell death signalling via NRAGE, NRIF and NADE;Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.220

Intolerance Scores

• loftool: 0.0693
• rvis_EVS: 1.99
• rvis_percentile_EVS: 97.64

Haploinsufficiency Scores

• pHI: 0.222
• hipred: N
• hipred_score: 0.429
• ghis: 0.440

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.956

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Akap13
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; immune system phenotype; embryo 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); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: protein phosphorylation;G protein-coupled receptor signaling pathway;heart development;positive regulation of Rho protein signal transduction;positive regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of MAP kinase activity;regulation of small GTPase mediated signal transduction;nuclear export;cardiac muscle cell differentiation;regulation of sarcomere organization;bone development;cell growth involved in cardiac muscle cell development;adrenergic receptor signaling pathway;adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process;regulation of glucocorticoid mediated signaling pathway
• Cellular component: nucleus;cytosol;actin filament;cell cortex;membrane;cortical actin cytoskeleton;perinuclear region of cytoplasm
• Molecular function: cAMP-dependent protein kinase activity;MAP-kinase scaffold activity;guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;protein binding;Rho GTPase binding;protein-containing complex scaffold activity;metal ion binding;protein kinase A binding