PKIB

Summary

PKIB (cAMP-dependent protein kinase inhibitor beta, HGNC:9018) is a protein-coding gene on chromosome 6q22.31, encoding cAMP-dependent protein kinase inhibitor beta (Q9C010). Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains.

This gene encodes a member of the cAMP-dependent protein kinase inhibitor family. The encoded protein may play a role in the protein kinase A (PKA) pathway by interacting with the catalytic subunit of PKA, and overexpression of this gene may play a role in prostate cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 5570 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 20 total
• MANE Select transcript: NM_181795

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9018
Approved symbol	PKIB
Name	cAMP-dependent protein kinase inhibitor beta
Location	6q22.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135549
Ensembl biotype	protein_coding
OMIM	606914
Entrez	5570

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 40 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000258014, ENST00000354275, ENST00000368446, ENST00000368448, ENST00000368452, ENST00000392490, ENST00000392491, ENST00000583007, ENST00000607474, ENST00000608895, ENST00000615438, ENST00000618977, ENST00000696716, ENST00000884759, ENST00000884760, ENST00000884761, ENST00000884762, ENST00000884763, ENST00000884764, ENST00000884765, ENST00000884766, ENST00000884767, ENST00000884768, ENST00000884769, ENST00000884770, ENST00000884771, ENST00000884772, ENST00000884773, ENST00000884774, ENST00000884775, ENST00000884776, ENST00000923510, ENST00000923511, ENST00000923512, ENST00000943366, ENST00000943367, ENST00000943368, ENST00000943369, ENST00000943370, ENST00000943371, ENST00000943372, ENST00000943373, ENST00000943374, ENST00000943375

RefSeq mRNA: 6 — MANE Select: NM_181795 NM_001270393, NM_001270394, NM_001270395, NM_032471, NM_181794, NM_181795

CCDS: CCDS5126, CCDS59033

Canonical transcript exons

ENST00000368452 — 5 exons

Exon	Start	End
ENSE00001425899	122675078	122675144
ENSE00001447151	122725128	122726373
ENSE00001447158	122633283	122633367
ENSE00003492527	122717787	122717963
ENSE00003849003	122610405	122610535

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 99.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1754 / max 763.2770, expressed in 1300 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69529	9.2880	836
69524	1.2126	670
69534	1.1830	240
69530	1.0453	322
69528	0.1603	63
69527	0.1158	62
69526	0.0967	45
69533	0.0377	14
69523	0.0361	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	99.10	gold quality
ileal mucosa	UBERON:0000331	98.96	gold quality
mucosa of transverse colon	UBERON:0004991	98.57	gold quality
cerebellar cortex	UBERON:0002129	98.36	gold quality
cerebellar hemisphere	UBERON:0002245	98.32	gold quality
cerebellum	UBERON:0002037	98.31	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.57	gold quality
colonic mucosa	UBERON:0000317	97.07	gold quality
rectum	UBERON:0001052	96.54	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.50	gold quality
placenta	UBERON:0001987	95.36	gold quality
bronchial epithelial cell	CL:0002328	94.62	gold quality
pons	UBERON:0000988	93.03	gold quality
bronchus	UBERON:0002185	92.39	gold quality
islet of Langerhans	UBERON:0000006	92.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.90	gold quality
jejunal mucosa	UBERON:0000399	89.73	gold quality
transverse colon	UBERON:0001157	89.51	gold quality
upper leg skin	UBERON:0004262	89.11	gold quality
pituitary gland	UBERON:0000007	86.30	gold quality
adenohypophysis	UBERON:0002196	86.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.26	gold quality
body of stomach	UBERON:0001161	85.27	gold quality
duodenum	UBERON:0002114	84.98	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.03	gold quality
colonic epithelium	UBERON:0000397	82.23	gold quality
stomach	UBERON:0000945	81.56	gold quality
large intestine	UBERON:0000059	81.49	gold quality
substantia nigra pars compacta	UBERON:0001965	81.47	gold quality
intestine	UBERON:0000160	81.42	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-GEOD-130148	yes	1030.57
E-MTAB-6653	yes	469.47
E-MTAB-6701	yes	129.62
E-MTAB-6911	yes	56.18
E-HCAD-31	yes	26.55
E-GEOD-125970	yes	26.47
E-MTAB-5061	yes	16.00
E-GEOD-81608	yes	15.89
E-MTAB-8410	yes	13.79
E-GEOD-81547	yes	13.21
E-CURD-114	yes	12.53
E-CURD-88	yes	11.81
E-ANND-3	yes	9.52
E-GEOD-83139	yes	9.04
E-MTAB-8060	no	325.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

77 targeting PKIB, 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-8485	100.00	77.57	4731
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4679	99.76	69.19	1229

Literature-anchored findings (GeneRIF, showing 9)

• human PKIbeta gene (clone 436F11, GenBank with accession number: AF225513) was over-expressed in normal brain tissues (PMID:12061725)
• PKIbeta may be a novel full-length gene related to human glioma and may provide a new way to gene therapy of glioma. (PMID:19035091)
• Findings show that PKIB and PKA-C kinase can have critical functions of aggressive phenotype of PCs through Akt phosphorylation and that they should be a promising molecular target for PC treatment. (PMID:19483721)
• Functional studies of the rat homolog (PMID:2052616)
• PKIB overexpression was strongly correlated with pAkt expression and triple-negative breast cancer, suggesting that PKIB overexpression might contribute to the tumor behavior and development of breast cancers. (PMID:23224602)
• mutation of the pseudosubstrate domain abolished the inhibitory activity of PKIB on protein kinase A activity, but had no effect on the interaction with GPR39, cell protection and induction of SRE-dependent transcription (PMID:24869658)
• results indicate that PKIB promotes cell proliferation and tumorigenesis by activating the PI3K/Akt pathway in non-small cell lung cancer (NSCLC), implying that this is an important underlying mechanism that affects the progression of NSCLC (PMID:27325557)
• Downregulation of cAMP-Dependent Protein Kinase Inhibitor-b Promotes Preeclampsia by Decreasing Phosphorylated Akt. (PMID:32676926)
• Functional studies of the mouse homolog (PMID:7684369)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pkib	ENSDARG00000053110
mus_musculus	Pkib	ENSMUSG00000019876
rattus_norvegicus	Pkib	ENSRNOG00000000811

Paralogs (2): PKIG (ENSG00000168734), PKIA (ENSG00000171033)

Protein

Protein identifiers

cAMP-dependent protein kinase inhibitor beta — Q9C010 (reviewed: Q9C010)

All UniProt accessions (3): A0A8Q3SIW0, Q9C010, Q5T0Z6

UniProt curated annotations — full annotation on UniProt →

Function. Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains.

Similarity. Belongs to the PKI family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9C010-1	1	yes
Q9C010-2	2

RefSeq proteins (6): NP_001257322, NP_001257323, NP_001257324, NP_115860, NP_861459, NP_861460* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004171	cAMP_dep_PKI	Family

Pfam: PF02827

UniProt features (9 total): compositionally biased region 3, site 3, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C010-F1	63.98	0.00

Functional residue map

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

Catalytic / active sites (3): 23 (important for inhibition); 26 (important for inhibition); 27 (important for inhibition)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 220 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_CHROMOSOME_ORGANIZATION, TGCGCANK_UNKNOWN, MODULE_418, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOZGIT_ESR1_TARGETS_DN, GOBP_TELOMERE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, LIAO_METASTASIS, GOBP_POSITIVE_REGULATION_OF_TELOMERE_MAINTENANCE, SABATES_COLORECTAL_ADENOMA_DN

GO Biological Process (2): positive regulation of telomere maintenance (GO:0032206), negative regulation of protein kinase activity (GO:0006469)

GO Molecular Function (3): cAMP-dependent protein kinase inhibitor activity (GO:0004862), protein kinase inhibitor activity (GO:0004860), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
telomere maintenance	1
regulation of telomere maintenance	1
positive regulation of DNA metabolic process	1
positive regulation of chromosome organization	1
negative regulation of protein phosphorylation	1
negative regulation of kinase activity	1
regulation of protein kinase activity	1
cAMP-dependent protein kinase activity	1
cAMP-dependent protein kinase regulator activity	1
protein serine/threonine kinase inhibitor activity	1
kinase inhibitor activity	1
protein kinase regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

669 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PKIB	PKIG	Q9Y2B9	638
PKIB	ZNF578	Q96N58	491
PKIB	GREB1	Q4ZG55	438
PKIB	DAP3	P51398	427
PKIB	S100A16	Q96FQ6	409
PKIB	HRNR	Q86YZ3	398
PKIB	TBC1D23	Q9NUY8	358
PKIB	IFT172	Q9UG01	353
PKIB	RNASEH1	O60930	353
PKIB	C4A	P01028	353
PKIB	SLC4A8	Q2Y0W8	353
PKIB	ZNF213	O14771	352
PKIB	DLGAP5	Q15398	348
PKIB	BUB1	O43683	342
PKIB	AURKA	O14965	330

IntAct

3 interactions, top by confidence:

A	B	Type	Score
LY6D	PKIB	psi-mi:“MI:0915”(physical association)	0.370
PKIB	PIN1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (9): PKIB (Two-hybrid), PKIB (Two-hybrid), PKIB (Two-hybrid), PKIB (Two-hybrid), KRTAP3-1 (Two-hybrid), SART1 (Cross-Linking-MS (XL-MS)), PKIB (Affinity Capture-RNA), PKIB (Two-hybrid), PKIB (Two-hybrid)

ESM2 similar proteins: A0A1B0GUA9, A0A1B0GV96, A4IFJ0, B3DGJ2, O43687, O55074, O70139, O75167, P04370, P0C8S0, P0C913, P0C914, P0CD96, P19103, P27775, P49342, P61925, P61926, P62025, P63248, P63249, Q04758, Q13522, Q29026, Q3SX13, Q3T0A6, Q3ZB98, Q4VC05, Q5FVI4, Q5R6X9, Q64256, Q6P3A1, Q71U53, Q7M2N1, Q7YQJ3, Q7YQJ4, Q8N111, Q8R409, Q8TAD7, Q8WMS3

Diamond homologs: P27775, P61925, P61926, P63248, P63249, Q04758, Q3SX13, Q71U53, Q9C010, O70139, Q7YQJ3, Q7YQJ4, Q90641, Q9Y2B9

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	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2620 predictions. Top by Δscore:

Variant	Effect	Δscore
6:122633277:CTTCA:C	acceptor_loss	1.0000
6:122633278:TTCA:T	acceptor_loss	1.0000
6:122633279:TCA:T	acceptor_loss	1.0000
6:122633280:CAG:C	acceptor_loss	1.0000
6:122633281:A:AG	acceptor_gain	1.0000
6:122633281:A:AT	acceptor_loss	1.0000
6:122633281:AG:A	acceptor_gain	1.0000
6:122633282:G:GG	acceptor_gain	1.0000
6:122633282:G:GT	acceptor_loss	1.0000
6:122633282:GG:G	acceptor_gain	1.0000
6:122633282:GGA:G	acceptor_gain	1.0000
6:122633282:GGAGT:G	acceptor_gain	1.0000
6:122633363:TAGGA:T	donor_gain	1.0000
6:122633364:AGGA:A	donor_gain	1.0000
6:122633365:GGA:G	donor_gain	1.0000
6:122633365:GGAG:G	donor_gain	1.0000
6:122633366:GA:G	donor_gain	1.0000
6:122633366:GAG:G	donor_gain	1.0000
6:122633366:GAGTA:G	donor_loss	1.0000
6:122633367:AG:A	donor_loss	1.0000
6:122633368:G:GG	donor_gain	1.0000
6:122633369:TAAG:T	donor_loss	1.0000
6:122633370:AA:A	donor_loss	1.0000
6:122717959:GGAAG:G	donor_gain	1.0000
6:122717960:G:GT	donor_gain	1.0000
6:122717961:A:T	donor_gain	1.0000
6:122472019:T:TA	donor_gain	0.9900
6:122472020:A:AA	donor_gain	0.9900
6:122472042:GT:G	donor_gain	0.9900
6:122477849:A:AG	acceptor_gain	0.9900

AlphaMissense

500 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:122717870:C:A	R26S	0.978
6:122717846:T:C	F18L	0.970
6:122717848:T:A	F18L	0.970
6:122717848:T:G	F18L	0.970
6:122717878:T:A	N28K	0.957
6:122717878:T:G	N28K	0.957
6:122717874:G:C	R27P	0.956
6:122717863:G:C	R23S	0.955
6:122717863:G:T	R23S	0.955
6:122717847:T:G	F18C	0.947
6:122717868:G:A	G25D	0.946
6:122717871:G:C	R26P	0.938
6:122717867:G:C	G25R	0.937
6:122717870:C:G	R26G	0.929
6:122717867:G:T	G25C	0.924
6:122717880:C:A	A29D	0.903
6:122717873:C:G	R27G	0.902
6:122717862:G:C	R23T	0.901
6:122717862:G:T	R23M	0.899
6:122717874:G:T	R27L	0.893
6:122717868:G:T	G25V	0.892
6:122717879:G:C	A29P	0.892
6:122717877:A:T	N28I	0.888
6:122717871:G:T	R26L	0.879
6:122717870:C:T	R26C	0.876
6:122717876:A:G	N28D	0.874
6:122717877:A:C	N28T	0.872
6:122717847:T:C	F18S	0.867
6:122717861:A:G	R23G	0.861
6:122717892:T:C	I33T	0.855

dbSNP variants (sampled 300 via entrez): RS1000000071 (6:122545977 A>G), RS1000012417 (6:122542469 G>A,T), RS1000042949 (6:122508310 G>A), RS1000051231 (6:122680811 C>T), RS1000062978 (6:122590770 G>C), RS1000063206 (6:122542611 G>A), RS1000065327 (6:122544186 A>G), RS1000067511 (6:122498827 A>C), RS1000087367 (6:122645847 T>A,C), RS1000095932 (6:122723559 A>G), RS1000111374 (6:122472984 C>T), RS1000113609 (6:122590475 T>C), RS1000125973 (6:122704101 G>C), RS1000137306 (6:122726555 T>C), RS1000160799 (6:122565289 T>C)

Disease associations

OMIM: gene MIM:606914 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST90002390_449	Mean corpuscular hemoglobin	1.000000e-11
GCST90002392_696	Mean corpuscular volume	2.000000e-16
GCST90002393_91	Monocyte count	9.000000e-16
GCST90002396_338	Mean reticulocyte volume	1.000000e-13
GCST90002397_478	Mean spheric corpuscular volume	5.000000e-13
GCST90002407_271	White blood cell count	6.000000e-19

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0005091	monocyte count
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases methylation	3
trichostatin A	affects cotreatment, increases expression	2
sodium arsenite	increases expression, affects methylation	2
Acetaminophen	decreases expression, increases expression	2
Coumestrol	affects cotreatment, increases expression, affects reaction	2
Tobacco Smoke Pollution	decreases expression	2
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
ochratoxin A	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
aflatoxin B2	increases methylation	1
indeno(1,2,3-cd)pyrene	decreases expression	1
picene	decreases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	decreases expression	1
Troglitazone	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1

Clinical trials (associated diseases)

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