AKAP14

Summary

AKAP14 (A-kinase anchoring protein 14, HGNC:24061) is a protein-coding gene on chromosome Xq24, encoding A-kinase anchor protein 14 (Q86UN6). Binds to type II regulatory subunits of protein kinase A and anchors/targets them.

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 protein anchors PKA in ciliary axonemes and, in this way, may play a role in regulating ciliary beat frequency. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 158798 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 37 total — 2 pathogenic
• MANE Select transcript: NM_178813

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24061
Approved symbol	AKAP14
Name	A-kinase anchoring protein 14
Location	Xq24
Locus type	gene with protein product
Status	Approved
Aliases	AKAP28
Ensembl gene	ENSG00000186471
Ensembl biotype	protein_coding
OMIM	300462
Entrez	158798

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000334356, ENST00000371422, ENST00000371425, ENST00000371431, ENST00000491105, ENST00000863386, ENST00000863387, ENST00000919408

RefSeq mRNA: 3 — MANE Select: NM_178813 NM_001008534, NM_001008535, NM_178813

CCDS: CCDS14591, CCDS35376, CCDS35377

Canonical transcript exons

ENST00000371431 — 7 exons

Exon	Start	End
ENSE00001338729	119914699	119914878
ENSE00001338796	119919911	119919963
ENSE00001338800	119903495	119903586
ENSE00001338802	119903214	119903392
ENSE00001413756	119896155	119896267
ENSE00003621511	119920508	119920716
ENSE00003893294	119895893	119895987

Expression profiles

Bgee: expression breadth ubiquitous, 146 present calls, max score 98.72.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3346 / max 60.8965, expressed in 96 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197410	0.3118	96
197409	0.0228	3

Top tissues by expression

244 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	98.72	gold quality
bronchus	UBERON:0002185	98.11	gold quality
right uterine tube	UBERON:0001302	96.84	gold quality
oviduct epithelium	UBERON:0004804	95.84	gold quality
left testis	UBERON:0004533	95.40	gold quality
right testis	UBERON:0004534	95.21	gold quality
sperm	CL:0000019	95.13	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.53	gold quality
testis	UBERON:0000473	92.60	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.36	gold quality
epithelium of nasopharynx	UBERON:0001951	89.82	gold quality
fallopian tube	UBERON:0003889	85.26	gold quality
nasal cavity epithelium	UBERON:0005384	81.84	gold quality
nasal cavity mucosa	UBERON:0001826	76.42	gold quality
trachea	UBERON:0003126	75.94	gold quality
caput epididymis	UBERON:0004358	72.00	gold quality
adult organism	UBERON:0007023	69.94	gold quality
right lung	UBERON:0002167	66.81	gold quality
hypothalamus	UBERON:0001898	65.72	gold quality
amygdala	UBERON:0001876	62.91	gold quality
endometrium	UBERON:0001295	61.09	gold quality
lower lobe of lung	UBERON:0008949	60.87	silver quality
left uterine tube	UBERON:0001303	60.07	gold quality
ganglionic eminence	UBERON:0004023	58.50	gold quality
prefrontal cortex	UBERON:0000451	55.36	gold quality
pancreatic ductal cell	CL:0002079	55.10	silver quality
cardiac muscle of right atrium	UBERON:0003379	55.01	gold quality
ileal mucosa	UBERON:0000331	54.98	silver quality
lung	UBERON:0002048	54.40	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	7.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting AKAP14, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-1227-3P	97.36	66.94	834

Literature-anchored findings (GeneRIF, showing 1)

• AKAP28 likely plays a role in the signaling necessary for efficient modulation of ciliary beat frequency (PMID:12475942)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkeyp-81f3.4	ENSDARG00000105458
mus_musculus	Akap14	ENSMUSG00000036551
rattus_norvegicus	Akap14	ENSRNOG00000006899

Protein

Protein identifiers

A-kinase anchor protein 14 — Q86UN6 (reviewed: Q86UN6)

Alternative names: A-kinase anchor protein 28 kDa, Protein kinase A-anchoring protein 14

All UniProt accessions (1): Q86UN6

UniProt curated annotations — full annotation on UniProt →

Function. Binds to type II regulatory subunits of protein kinase A and anchors/targets them.

Subunit / interactions. Binds to type II regulatory subunits (RII).

Subcellular location. Cytoplasm.

Tissue specificity. Present in cilia (at protein level). Expressed in tissues containing axoneme-based organelles (cilia and/or flagella): trachea and testis. Highly expressed in airway cilia.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86UN6-1	1, Isoform A	yes
Q86UN6-2	2, Isoform B
Q86UN6-3	3, Isoform C

RefSeq proteins (3): NP_001008534, NP_001008535, NP_848928* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025663	AKAP_28	Family
IPR053084	AKAP	Family

Pfam: PF14469

UniProt features (11 total): splice variant 3, region of interest 2, compositionally biased region 2, mutagenesis site 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86UN6-F1	78.55	0.35

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (2):

Position	Phenotype
43	abolishes rii-binding; when associated with p-47.
47	abolishes rii-binding; when associated with p-43.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 35 (showing top): SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GOCC_CYTOPLASMIC_REGION, GOCC_TRANSFERASE_COMPLEX, GOCC_PROTEIN_KINASE_COMPLEX, GOCC_CILIUM, GOMF_PROTEIN_KINASE_A_REGULATORY_SUBUNIT_BINDING, GOMF_PROTEIN_KINASE_A_BINDING, DODD_NASOPHARYNGEAL_CARCINOMA_DN, chrXq24, ZHOU_INFLAMMATORY_RESPONSE_FIMA_DN, GOCC_CAMP_DEPENDENT_PROTEIN_KINASE_COMPLEX, ZNF7_TARGET_GENES, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_2

GO Biological Process (0):

GO Molecular Function (2): protein kinase A regulatory subunit binding (GO:0034237), protein binding (GO:0005515)

GO Cellular Component (3): axoneme (GO:0005930), cAMP-dependent protein kinase complex (GO:0005952), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein kinase A binding	1
binding	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
intracellular protein-containing complex	1
serine/threonine protein kinase complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

546 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AKAP14	AKAP1	Q92667	787
AKAP14	PRKACA	P17612	456
AKAP14	PRKACB	P22694	456
AKAP14	PRKACG	P22612	456
AKAP14	AKAP4	Q5JQC9	430
AKAP14	KIAA1210	Q9ULL0	400
AKAP14	SPANXN3	Q5MJ09	380
AKAP14	RFTN2	Q52LD8	376
AKAP14	SPACA5B	Q96QH8	374
AKAP14	AKAP5	P24588	370
AKAP14	SPANXN5	Q5MJ07	370
AKAP14	AKAP3	O75969	367
AKAP14	RIBC1	Q8N443	366
AKAP14	IHO1	Q8IYA8	355
AKAP14	CYLC1	P35663	346

IntAct

26 interactions, top by confidence:

A	B	Type	Score
PRKAR2B	AKAP14	psi-mi:“MI:0915”(physical association)	0.740
AKAP14	ROPN1L	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	AKAP14	psi-mi:“MI:0915”(physical association)	0.560
AKAP14	DPY30	psi-mi:“MI:0915”(physical association)	0.560
AKAP14	ROPN1	psi-mi:“MI:0915”(physical association)	0.560
PRKAR2A	AKAP14	psi-mi:“MI:0915”(physical association)	0.560
AKAP14	PRKAR2A	psi-mi:“MI:0914”(association)	0.530
MYCBP	AKAP14	psi-mi:“MI:0915”(physical association)	0.370
AKAP14	EFCAB7	psi-mi:“MI:0914”(association)	0.350
AKAP14	PRKAR2B	psi-mi:“MI:0915”(physical association)	0.000
AKAP14	DPY30	psi-mi:“MI:0915”(physical association)	0.000
AKAP14	PRKAR1B	psi-mi:“MI:0915”(physical association)	0.000
ROPN1	AKAP14	psi-mi:“MI:0915”(physical association)	0.000
AKAP14	PRKAR2A	psi-mi:“MI:0915”(physical association)	0.000
PRKAR2B	AKAP14	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (43): ARL5B (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), PRKAR2B (Affinity Capture-MS), PRKAR2A (Affinity Capture-MS), PRKACA (Affinity Capture-MS), PRKACG (Affinity Capture-MS), PRKACB (Affinity Capture-MS), SPA17 (Affinity Capture-MS), SYNJ2BP (Affinity Capture-MS), OCIAD1 (Affinity Capture-MS), EFCAB7 (Affinity Capture-MS), PRKAR2B (Affinity Capture-MS), SPA17 (Affinity Capture-MS), PRKACB (Affinity Capture-MS), PRKACG (Affinity Capture-MS)

ESM2 similar proteins: A1AVW3, A1BDQ9, A1DPK7, A8G2V3, A8MGN0, A9A5W9, B3DQN7, B3EFT2, B3EM52, B3QLJ0, B4S4Y9, B4SCX8, B8CNS1, B8DHM6, C0SPB1, C4QGM3, O15145, O32042, O48397, P06942, P06944, P09877, P0C141, P0C571, P0CA85, P0CA86, P13844, P18611, P21000, P30909, P35976, P38475, P81375, Q01639, Q0A442, Q1WTX9, Q3AT43, Q3T035, Q4ZZG6, Q54EY1

Diamond homologs: O35817, Q86UN6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

37 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	22
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3370387	GRCh38/hg38 Xq24-25(chrX:119043046-123885987)x2	Pathogenic
3391959	GRCh37/hg19 Xq24(chrX:118660849-119137904)x1	Pathogenic

SpliceAI

868 predictions. Top by Δscore:

Variant	Effect	Δscore
X:119903209:CCCA:C	acceptor_loss	1.0000
X:119903210:CCA:C	acceptor_loss	1.0000
X:119903212:A:AG	acceptor_gain	1.0000
X:119903212:AG:A	acceptor_gain	1.0000
X:119903212:AGGA:A	acceptor_loss	1.0000
X:119903213:G:GG	acceptor_gain	1.0000
X:119903213:GG:G	acceptor_gain	1.0000
X:119903213:GGA:G	acceptor_gain	1.0000
X:119903323:G:GT	donor_gain	1.0000
X:119903359:G:GT	donor_gain	1.0000
X:119903378:T:G	donor_gain	1.0000
X:119903389:G:GT	donor_gain	1.0000
X:119903390:A:T	donor_gain	1.0000
X:119903392:GGT:G	donor_loss	1.0000
X:119903393:G:T	donor_gain	1.0000
X:119903393:GT:G	donor_loss	1.0000
X:119903394:T:A	donor_loss	1.0000
X:119903490:TGCA:T	acceptor_loss	1.0000
X:119903491:GCAGA:G	acceptor_loss	1.0000
X:119903492:CAGAG:C	acceptor_loss	1.0000
X:119903493:A:AG	acceptor_gain	1.0000
X:119903493:A:C	acceptor_loss	1.0000
X:119903493:AGAG:A	acceptor_gain	1.0000
X:119903494:G:GG	acceptor_gain	1.0000
X:119903494:GA:G	acceptor_gain	1.0000
X:119903494:GAGG:G	acceptor_gain	1.0000
X:119903494:GAGGA:G	acceptor_gain	1.0000
X:119914698:GAA:G	acceptor_gain	1.0000
X:119920506:A:AG	acceptor_gain	1.0000
X:119920507:G:GA	acceptor_gain	1.0000

AlphaMissense

1316 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:119903542:T:C	F73L	0.987
X:119903544:C:A	F73L	0.987
X:119903544:C:G	F73L	0.987
X:119903524:T:A	W67R	0.982
X:119903524:T:C	W67R	0.982
X:119903543:T:C	F73S	0.978
X:119903526:G:C	W67C	0.971
X:119903526:G:T	W67C	0.971
X:119914847:T:C	F137S	0.967
X:119914846:T:C	F137L	0.962
X:119914848:C:A	F137L	0.962
X:119914848:C:G	F137L	0.962
X:119914780:T:G	Y115D	0.957
X:119914768:T:C	F111L	0.951
X:119914770:C:A	F111L	0.951
X:119914770:C:G	F111L	0.951
X:119920524:T:C	F171L	0.945
X:119920526:T:A	F171L	0.945
X:119920526:T:G	F171L	0.945
X:119914765:A:C	S110R	0.943
X:119914767:C:A	S110R	0.943
X:119914767:C:G	S110R	0.943
X:119903558:G:A	G78D	0.937
X:119903557:G:C	G78R	0.936
X:119903543:T:G	F73C	0.927
X:119914792:T:A	W119R	0.927
X:119914792:T:C	W119R	0.927
X:119919927:T:A	V153D	0.927
X:119914774:T:G	Y113D	0.923
X:119914722:G:C	W95C	0.918

dbSNP variants (sampled 300 via entrez): RS1000172187 (X:119919010 T>C), RS1000234920 (X:119917958 T>C), RS1000339370 (X:119899930 A>C,G), RS1000360202 (X:119903912 T>C), RS1000383639 (X:119909817 G>A), RS1000443820 (X:119900298 G>A), RS1000603979 (X:119911396 C>T), RS1000663021 (X:119901915 A>G), RS1000685142 (X:119909453 G>A), RS1001120937 (X:119911876 C>G), RS1001235613 (X:119907452 T>C), RS1001344570 (X:119897441 G>C,T), RS1001363072 (X:119906378 G>A), RS1001628561 (X:119916582 C>T), RS1001740661 (X:119921071 G>T)

Disease associations

OMIM: gene MIM:300462 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): intellectual disability (MONDO:0001071)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Tobacco Smoke Pollution	decreases expression	2
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
entinostat	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Methapyrilene	increases methylation	1
Smoke	increases abundance, increases expression	1

Clinical trials (associated diseases)

197 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders