AKAP6

protein-coding

A-kinase anchoring protein 6, 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 highly expressed in various brain regions and cardiac and skeletal muscle. It is specifically localized to the sarcoplasmic reticulum and nuclear membrane, and is involved in anchoring PKA to the nuclear membrane or sarcoplasmic reticulum. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004274.5

Inheritance

ClinVar variants

U:330B:25

Top phenotype

AKAP6-related disorder

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr14:32,329,298-32,837,684

External References & Databases

Ensembl (ENSG00000151320)

Transcript & Mutation Effects

hg38 • Region Span ~508.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AKAP6 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 305

not providedTotal: 15

AKAP6-related disorderTotal: 1

AKAP6-related Intellectual DisabilityTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004274.5. 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			7 clinvar	3 clinvar	1 clinvar	11
missense			309 clinvar	18 clinvar	3 clinvar	330
nonsense			9 clinvar			9
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	330	21	4	355

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004274.5	RefSeq	NP_004265.3	12	MANE Select
ENST00000280979.9	Ensembl	ENSP00000280979.4	12	MANE Select
ENST00000553547.5	Ensembl	ENSP00000451239.1	1	Standard
ENST00000554410.5	Ensembl	ENSP00000451246.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

G Protein Signaling Pathways

Biological Process

action potential
protein targeting
regulation of protein kinase A signaling
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
cAMP-mediated signaling

Molecular Function

protein binding
adenylate cyclase binding
protein-containing complex scaffold activity
protein kinase A regulatory subunit binding
protein membrane anchor

Cellular Component

nuclear envelope
cytoplasm
caveola
junctional sarcoplasmic reticulum membrane
intercalated disc

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000280979
Coding exons: 12
Length: 502089
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125743
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0427	1195	1.19e+3	1.00	0.0000604	15338
Missense (PolyPhen)		437	483.35	0.90411		6369
Synonymous	-1.00	484	457	1.06	0.0000244	4426
Loss of Function	7.22	14	86.5	0.162	0.00000492	1096

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the nuclear membrane or sarcoplasmic reticulum. May act as an adapter for assembling multiprotein complexes.;

Recessive Scores

pRec: 0.127

Intolerance Scores

LoFtool: 0.282
RVIS EVS: 0.3
RVIS percentile EVS: 71.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.525

Gene Damage Prediction

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