AKAIN1

Summary

AKAIN1 (A-kinase anchor inhibitor 1, HGNC:28285) is a protein-coding gene on chromosome 18p11.31, encoding A-kinase anchor protein inhibitor 1 (P0CW23). Protein kinase A (PKA)-binding protein.

Enables protein kinase A binding activity. Involved in protein localization. Predicted to be located in cytosol.

Source: NCBI Gene 642597 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 20 total — 7 pathogenic
• MANE Select transcript: NM_001145194

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28285
Approved symbol	AKAIN1
Name	A-kinase anchor inhibitor 1
Location	18p11.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000231824
Ensembl biotype	protein_coding
OMIM	616427
Entrez	642597

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000434239, ENST00000580650

RefSeq mRNA: 2 — MANE Select: NM_001145194 NM_001145194, NM_001330553

CCDS: CCDS54179, CCDS82235

Canonical transcript exons

ENST00000434239 — 2 exons

Exon	Start	End
ENSE00002321816	5197038	5197257
ENSE00002726727	5142911	5145755

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 91.52.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3506 / max 87.1123, expressed in 73 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171090	0.1553	42
171087	0.0867	30
171089	0.0865	33
171088	0.0220	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	91.52	gold quality
cerebellar cortex	UBERON:0002129	91.49	gold quality
cerebellum	UBERON:0002037	90.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.85	gold quality
islet of Langerhans	UBERON:0000006	85.91	gold quality
ganglionic eminence	UBERON:0004023	82.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.37	gold quality
cerebellar vermis	UBERON:0004720	73.60	gold quality
lateral nuclear group of thalamus	UBERON:0002736	72.32	gold quality
Ammon’s horn	UBERON:0001954	68.97	gold quality
prefrontal cortex	UBERON:0000451	66.08	gold quality
Brodmann (1909) area 23	UBERON:0013554	65.86	silver quality
primary visual cortex	UBERON:0002436	65.07	gold quality
middle temporal gyrus	UBERON:0002771	64.39	silver quality
pituitary gland	UBERON:0000007	62.89	gold quality
buccal mucosa cell	CL:0002336	61.95	silver quality
adenohypophysis	UBERON:0002196	61.50	gold quality
anterior cingulate cortex	UBERON:0009835	61.34	gold quality
Brodmann (1909) area 9	UBERON:0013540	61.16	gold quality
right frontal lobe	UBERON:0002810	61.06	gold quality
cerebral cortex	UBERON:0000956	60.91	gold quality
neocortex	UBERON:0001950	60.90	gold quality
frontal cortex	UBERON:0001870	60.83	gold quality
ventricular zone	UBERON:0003053	60.55	gold quality
pancreas	UBERON:0001264	60.41	gold quality
pons	UBERON:0000988	60.37	silver quality
brain	UBERON:0000955	59.97	gold quality
occipital lobe	UBERON:0002021	59.28	gold quality
lateral globus pallidus	UBERON:0002476	58.85	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	58.66	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

100 targeting AKAIN1, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-8067	99.86	69.59	2260

Literature-anchored findings (GeneRIF, showing 1)

• These findings suggest that C18orf42 may be a novel PKA signaling gene that serves as an endogenous disruptor peptide for PKA-AKAP interactions. (PMID:25653177)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Akain1	ENSMUSG00000091636
rattus_norvegicus	Akain1	ENSRNOG00000063808

Paralogs (1): AKAP7 (ENSG00000118507)

Protein

Protein identifiers

A-kinase anchor protein inhibitor 1 — P0CW23 (reviewed: P0CW23)

All UniProt accessions (2): P0CW23, J3KS16

UniProt curated annotations — full annotation on UniProt →

Function. Protein kinase A (PKA)-binding protein. Binds to type II regulatory subunits of protein kinase A (PKA) and may block the A-kinase anchoring protein (AKAP)-mediated subcellular localization of PKA.

Subunit / interactions. Binds cAMP-dependent protein kinase (PKA). Interacts specifically with RII-regulatory subunits of PKA (PRKAR2A and PRKAR2B).

Tissue specificity. Preferentially expressed in the neural tissues.

Domain organisation. The RII-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer.

RefSeq proteins (2): NP_001138666, NP_001317482 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019511	AKAP7_RI-RII-bd_dom	Domain

Pfam: PF10470

UniProt features (5 total): region of interest 2, chain 1, compositionally biased region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0CW23-F1	75.59	0.31

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 (1):

Position	Phenotype
25	reduces binding to rii subunits of pka.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 36 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOMF_PROTEIN_KINASE_A_BINDING, HMG20B_TARGET_GENES, MIER1_TARGET_GENES, ZNF766_TARGET_GENES, ZSCAN30_TARGET_GENES, MIR607, MIR335_3P, MIR4803, MIR545_3P, MIR29B_3P_MIR29C_3P, MIR29A_3P

GO Biological Process (3): intracellular protein localization (GO:0008104), negative regulation of protein-containing complex assembly (GO:0031333), protein-containing complex assembly (GO:0065003)

GO Molecular Function (2): protein kinase A binding (GO:0051018), protein binding (GO:0005515)

GO Cellular Component (1): cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
macromolecule localization	1
regulation of protein-containing complex assembly	1
negative regulation of cellular component organization	1
protein-containing complex assembly	1
cellular component assembly	1
protein-containing complex organization	1
protein binding	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

124 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AKAIN1	CLUL1	Q15846	609
AKAIN1	L3MBTL4	Q8NA19	570
AKAIN1	ARHGAP28	Q9P2N2	541
AKAIN1	ENOSF1	Q7L5Y1	516
AKAIN1	PRELID3A	Q96N28	480
AKAIN1	MAB21L3	Q8N8X9	480
AKAIN1	ZBTB14	O43829	438
AKAIN1	THOC1	Q96FV9	431
AKAIN1	TXNDC2	Q86VQ3	431
AKAIN1	CETN1	Q12798	419
AKAIN1	SMCHD1	A6NHR9	417
AKAIN1	MYOM1	P52179	417
AKAIN1	COLEC12	Q5KU26	412
AKAIN1	PTPRM	P28827	398
AKAIN1	LPIN2	Q92539	391
AKAIN1	SLC22A15	Q8IZD6	391

IntAct

4 interactions, top by confidence:

A	B	Type	Score
AKAIN1	ROPN1	psi-mi:“MI:0915”(physical association)	0.560
ROPN1	AKAIN1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (1): C18orf42 (Two-hybrid)

ESM2 similar proteins: A1L3H4, A7SPE8, A9ULR1, C1CZ29, O71026, P03488, P07389, P07533, P0CU43, P0CU44, P0CU51, P0CU52, P0CW23, P12436, P15234, P22047, P25179, P30209, P33475, P69363, P69364, Q01175, Q02168, Q08454, Q18012, Q1J1S9, Q37887, Q3TC33, Q3V4Q3, Q3ZC61, Q4R8E8, Q4V8S9, Q54ID4, Q57780, Q5M820, Q68Y31, Q6PEB9, Q6R7D7, Q82037, Q82681

Diamond homologs: G3UWD5, P0CW23, O43687, O55074, Q6JP77, Q7TN79, Q9P0M2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	0
Uncertain significance	10
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
147396	GRCh38/hg38 18p11.32-11.21(chr18:2425507-11904118)x3	Pathogenic
1526599	GRCh37/hg19 18p11.31-11.23(chr18:3532742-7487522)	Pathogenic
154072	GRCh38/hg38 18p11.32-11.21(chr18:958974-11954935)x1	Pathogenic
442363	GRCh37/hg19 18p11.32-11.31(chr18:2666704-5267842)x1	Pathogenic
442451	GRCh37/hg19 18p11.32-q21.1(chr18:136227-46171053)x3	Pathogenic
59917	GRCh38/hg38 18p11.32-11.31(chr18:2547398-6694867)x1	Pathogenic
816496	GRCh37/hg19 18p11.32-11.21(chr18:13034-15330525)x1	Pathogenic

SpliceAI

788 predictions. Top by Δscore:

Variant	Effect	Δscore
18:5145761:C:T	acceptor_gain	1.0000
18:5145767:C:CT	acceptor_gain	1.0000
18:5145768:A:AC	acceptor_gain	1.0000
18:5145768:A:C	acceptor_gain	1.0000
18:5145751:CTCAC:C	acceptor_gain	0.9900
18:5145752:TCAC:T	acceptor_gain	0.9900
18:5145753:CAC:C	acceptor_gain	0.9900
18:5145753:CACC:C	acceptor_gain	0.9900
18:5145754:AC:A	acceptor_gain	0.9900
18:5145755:CC:C	acceptor_gain	0.9900
18:5145756:C:CA	acceptor_loss	0.9900
18:5145757:T:G	acceptor_loss	0.9900
18:5145761:C:CT	acceptor_gain	0.9900
18:5145762:A:T	acceptor_gain	0.9900
18:5145768:A:T	acceptor_gain	0.9900
18:5145756:C:CC	acceptor_gain	0.9800
18:5145767:CA:C	acceptor_loss	0.9800
18:5165486:TCTTG:T	donor_gain	0.9800
18:5196558:C:A	donor_gain	0.9800
18:5197032:GTGTA:G	donor_loss	0.9800
18:5197033:TGTAC:T	donor_loss	0.9800
18:5197034:GTACC:G	donor_loss	0.9800
18:5197035:TACC:T	donor_loss	0.9800
18:5197036:A:T	donor_loss	0.9800
18:5197037:C:CT	donor_loss	0.9800
18:5147938:T:TA	donor_gain	0.9700
18:5147526:C:CT	donor_gain	0.9600
18:5147527:T:TT	donor_gain	0.9600
18:5145752:TCACC:T	acceptor_gain	0.9500
18:5196281:T:TA	donor_gain	0.9500

AlphaMissense

455 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:5145706:G:C	S22R	0.990
18:5145706:G:T	S22R	0.990
18:5145708:T:G	S22R	0.990
18:5145675:C:G	A33P	0.983
18:5145683:A:G	I30T	0.983
18:5145683:A:T	I30N	0.980
18:5145687:C:G	A29P	0.977
18:5145683:A:C	I30S	0.973
18:5197045:G:C	F3L	0.971
18:5197045:G:T	F3L	0.971
18:5197047:A:G	F3L	0.971
18:5145695:A:T	V26E	0.964
18:5145698:A:C	I25S	0.959
18:5145674:G:T	A33D	0.953
18:5145707:C:A	S22I	0.953
18:5145719:A:G	L18P	0.942
18:5145698:A:T	I25N	0.940
18:5145707:C:T	S22N	0.927
18:5145703:T:A	K23N	0.917
18:5145703:T:G	K23N	0.917
18:5145695:A:G	V26A	0.913
18:5145680:A:G	L31P	0.908
18:5145695:A:C	V26G	0.904
18:5145692:T:G	Q27P	0.897
18:5145686:G:T	A29E	0.893
18:5145711:C:G	A21P	0.891
18:5145719:A:T	L18Q	0.884
18:5145698:A:G	I25T	0.882
18:5197046:A:C	F3C	0.874
18:5145696:C:A	V26L	0.862

dbSNP variants (sampled 300 via entrez): RS1000002903 (18:5156437 T>C), RS1000077628 (18:5180740 A>G), RS1000138035 (18:5174096 C>G,T), RS1000158788 (18:5157334 T>C), RS1000162947 (18:5198620 C>T), RS1000275213 (18:5157027 C>A,G), RS1000343903 (18:5198944 A>C,G,T), RS1000364222 (18:5150997 T>G), RS1000433904 (18:5151815 T>C), RS1000466212 (18:5174620 A>G), RS1000494074 (18:5180961 G>C), RS1000495366 (18:5155779 A>G), RS1000613577 (18:5197578 A>G,T), RS1000634942 (18:5157764 C>G), RS1000674442 (18:5191219 T>A)

Disease associations

OMIM: gene MIM:616427 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002806_12	Type 2 diabetes	3.000000e-06
GCST007565_205	Morning person	7.000000e-19
GCST007576_333	Chronotype	7.000000e-19
GCST011352_7	Alanine aminotransferase levels	3.000000e-08
GCST90000015_28	Parkinson’s disease motor subtype (tremor to postural instability/gait difficulty score ratio)	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0600011	Parkinson’s disease symptom measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	2
Vorinostat	decreases expression	1
Methotrexate	increases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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