AKAP12

protein-coding

A-kinase anchoring protein 12, the group of A-kinase anchoring proteins

Gene summary

The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is expressed in endothelial cells, cultured fibroblasts, and osteosarcoma cells. It associates with protein kinases A and C and phosphatase, and serves as a scaffold protein in signal transduction. This protein and RII PKA colocalize at the cell periphery. This protein is a cell growth-related protein. Antibodies to this protein can be produced by patients with myasthenia gravis. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005100.4

Inheritance

—

ClinVar variants

U:253B:35

Top phenotype

Preeclampsia

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr6:151,239,967-151,358,559

External References & Databases

Ensembl (ENSG00000131016)

Transcript & Mutation Effects

hg38 • Region Span ~118.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AKAP12 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 261

not providedTotal: 23

PreeclampsiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005100.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	2 clinvar	6 clinvar	9
missense			251 clinvar	22 clinvar	5 clinvar	278
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	253	24	11	288

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005100.4	RefSeq	NP_005091.2	3	MANE Select
ENST00000402676.7	Ensembl	ENSP00000384537.2	3	MANE Select
NM_001370346.1	RefSeq	NP_001357275.1	2	Standard
NM_144497.2	RefSeq	NP_653080.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
akap12b	Danio rerio	Structure: mesodermal cell Quality: increased amount abnormal

Gene / Model

Organism

Observed Phenotype

akap12b

Danio rerio

Structure: mesodermal cell

Quality: increased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

G Protein Signaling Pathways

Biological Process

protein targeting
G protein-coupled receptor signaling pathway
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
regulation of protein kinase A signaling
positive regulation of protein kinase A signaling

Molecular Function

protein binding
adenylate cyclase binding
protein kinase A binding

Cellular Component

cytoplasm
cytosol
cytoskeleton
plasma membrane
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000402676
Coding exons: 3
Length: 118559
Individuals with no LoFs: 125713
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 125748
p: 0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.575	882	931	0.947	0.0000516	11583
Missense (PolyPhen)		205	237.74	0.86228		2922
Synonymous	-0.125	395	392	1.01	0.0000271	3557
Loss of Function	4.61	12	45.6	0.263	0.00000207	671

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00043	0.00027	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.000099	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC).;

Recessive Scores

pRec: 0.118

Intolerance Scores

LoFtool: 0.536
RVIS EVS: 0.91
RVIS percentile EVS: 89.55

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.719

Gene Damage Prediction

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