AKAP3

protein-coding

A-kinase anchoring protein 3, the group of A-kinase anchoring proteins

Gene summary

This gene encodes a member of A-kinase anchoring proteins (AKAPs), a family of functionally related proteins that target protein kinase A to discrete locations within the cell. The encoded protein is reported to participate in protein-protein interactions with the R-subunit of the protein kinase A as well as sperm-associated proteins. This protein is expressed in spermatozoa and localized to the acrosomal region of the sperm head as well as the length of the principal piece. It may function as a regulator of motility, capacitation, and the acrosome reaction. [provided by RefSeq, May 2013]

MANE transcript

NM_001278309.2

Inheritance

ClinVar variants

P:3U:121B:14

Top phenotype

Spermatogenic failure 82

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr12:4,615,508-4,649,051

External References & Databases

Ensembl (ENSG00000111254)

Transcript & Mutation Effects

hg38 • Region Span ~33.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 82LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0957249

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spermatogenic failure 82AR

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 35228300

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AKAP3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 122

not providedTotal: 4

Spermatogenic failure 82Total: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001278309.2. 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	2 clinvar	5
missense		1 clinvar	118 clinvar	10 clinvar		129
nonsense						0
start loss						0
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	2	121	12	2	138

Highest pathogenic variant AF is 0.000099781966

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001278309.2	RefSeq	NP_001265238.2	3	MANE Select
ENST00000228850.6	Ensembl	ENSP00000228850.1	3	MANE Select
NM_006422.4	RefSeq	NP_006413.4	3	Standard
ENST00000536414.3	Ensembl	ENSP00000439382.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

G Protein Signaling Pathways

Biological Process

blastocyst hatching
transmembrane receptor protein serine/threonine kinase signaling pathway
single fertilization
acrosome reaction
protein localization

Molecular Function

protein binding
protein kinase A binding

Cellular Component

acrosomal vesicle
nucleus
cytoplasm
sperm fibrous sheath
sperm principal piece

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000545990
Coding exons: 3
Length: 33540
Individuals with no LoFs: 94395
Homozygous LoFs: 2566
Heterozygous LoFs: 28787
Defined: 125748
p: 0.134

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.468	441	470	0.939	0.0000248	5618
Missense (PolyPhen)		167	184.05	0.90734		2389
Synonymous	1.42	160	184	0.867	0.0000104	1678
Loss of Function	3.32	7	24.9	0.281	0.00000121	348

Population LoF Frequency

Population	CAF	p-value	Status
African	0.24	0.12	notable
Latino/Admixed American	0.24	0.12	notable
Ashkenazi Jewish	0.26	0.13	notable
East Asian	0.27	0.13	notable
Finnish	0.16	0.083	notable
European (Non-Finnish)	0.24	0.12	notable
South Asian	0.52	0.25	notable
Other	0.27	0.13	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function as a regulator of both motility- and head- associated functions such as capacitation and the acrosome reaction.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.775
RVIS EVS: 1.21
RVIS percentile EVS: 93.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.420

Gene Damage Prediction

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