PKIG

Summary

PKIG (cAMP-dependent protein kinase inhibitor gamma, HGNC:9019) is a protein-coding gene on chromosome 20q13.12, encoding cAMP-dependent protein kinase inhibitor gamma (Q9Y2B9). 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 protein kinase inhibitor family. Studies of a similar protein in mice suggest that this protein acts as a potent competitive cAMP-dependent protein kinase inhibitor, and is a predominant form of inhibitor in various tissues. The encoded protein may be involved in osteogenesis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 11142 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_001281445

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9019
Approved symbol	PKIG
Name	cAMP-dependent protein kinase inhibitor gamma
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000168734
Ensembl biotype	protein_coding
OMIM	604932
Entrez	11142

Gene structure

Transcript identifiers

Ensembl transcripts: 78 — 77 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000349959, ENST00000372886, ENST00000372887, ENST00000372889, ENST00000372891, ENST00000372892, ENST00000372894, ENST00000477390, ENST00000902612, ENST00000902613, ENST00000902614, ENST00000902615, ENST00000902616, ENST00000902617, ENST00000902618, ENST00000902619, ENST00000902620, ENST00000902621, ENST00000902622, ENST00000902623, ENST00000902624, ENST00000902625, ENST00000902626, ENST00000902627, ENST00000902628, ENST00000902629, ENST00000902630, ENST00000902631, ENST00000902632, ENST00000902633, ENST00000902634, ENST00000902635, ENST00000902636, ENST00000902637, ENST00000902638, ENST00000902639, ENST00000902640, ENST00000902641, ENST00000902642, ENST00000902643, ENST00000902644, ENST00000902645, ENST00000902646, ENST00000902647, ENST00000902648, ENST00000902649, ENST00000902650, ENST00000902651, ENST00000902652, ENST00000902653, ENST00000902654, ENST00000902655, ENST00000926460, ENST00000926461, ENST00000962966, ENST00000962967, ENST00000962968, ENST00000962969, ENST00000962970, ENST00000962971, ENST00000962972, ENST00000962973, ENST00000962974, ENST00000962975, ENST00000962976, ENST00000962977, ENST00000962978, ENST00000962979, ENST00000962980, ENST00000962981, ENST00000962982, ENST00000962983, ENST00000962984, ENST00000962985, ENST00000962986, ENST00000962987, ENST00000962988, ENST00000962989

RefSeq mRNA: 5 — MANE Select: NM_001281445 NM_001281444, NM_001281445, NM_007066, NM_181804, NM_181805

CCDS: CCDS13334

Canonical transcript exons

ENST00000372886 — 4 exons

Exon	Start	End
ENSE00001126435	44618285	44619037
ENSE00001458894	44614534	44614707
ENSE00001458898	44582579	44582731
ENSE00001458930	44589797	44589866

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.4050 / max 200.7328, expressed in 1699 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184733	20.6908	1647
184736	11.1113	1103
184732	0.3219	160
184737	0.1451	72
184735	0.0810	21
184734	0.0549	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right coronary artery	UBERON:0001625	98.87	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.69	gold quality
lower esophagus	UBERON:0013473	98.66	gold quality
heart right ventricle	UBERON:0002080	98.61	gold quality
apex of heart	UBERON:0002098	98.58	gold quality
coronary artery	UBERON:0001621	98.57	gold quality
left coronary artery	UBERON:0001626	98.56	gold quality
right atrium auricular region	UBERON:0006631	98.54	gold quality
cardiac atrium	UBERON:0002081	98.53	gold quality
cardiac ventricle	UBERON:0002082	98.44	gold quality
heart left ventricle	UBERON:0002084	98.44	gold quality
myocardium	UBERON:0002349	98.43	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.41	gold quality
vena cava	UBERON:0004087	98.38	gold quality
mucosa of stomach	UBERON:0001199	98.28	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.24	gold quality
heart	UBERON:0000948	98.21	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.20	gold quality
popliteal artery	UBERON:0002250	98.11	gold quality
tibial artery	UBERON:0007610	98.11	gold quality
saphenous vein	UBERON:0007318	98.07	gold quality
right lung	UBERON:0002167	97.86	gold quality
adult organism	UBERON:0007023	97.82	gold quality
aorta	UBERON:0000947	97.72	gold quality
left uterine tube	UBERON:0001303	97.59	gold quality
body of uterus	UBERON:0009853	97.59	gold quality
endocervix	UBERON:0000458	97.57	gold quality
myometrium	UBERON:0001296	97.28	gold quality
ascending aorta	UBERON:0001496	97.27	gold quality
thoracic aorta	UBERON:0001515	97.23	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	138.35
E-HCAD-6	yes	51.57
E-GEOD-135922	yes	24.17
E-CURD-122	yes	20.41
E-CURD-112	yes	8.68
E-MTAB-6142	no	104.03
E-MTAB-9388	no	9.01
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYCN

miRNA regulators (miRDB)

54 targeting PKIG, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-8066	99.05	68.66	1532

Literature-anchored findings (GeneRIF, showing 4)

• Functional studies of the mouse homolog (PMID:11742798)
• These results indicate that the downregulation of PKIgamma may be prerequisite for the PKA activation during the osteoblastic differentiation of precursor cells. (PMID:16870489)
• Results show that endogenous levels of Pkig reciprocally regulate osteoblast and adipocyte differentiation and that this reciprocal regulation is mediated in part by LIF. (PMID:23963683)
• Functional studies of the mouse homolog (PMID:9218452)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pkig	ENSDARG00000086471
mus_musculus	Pkig	ENSMUSG00000035268
rattus_norvegicus	Pkig	ENSRNOG00000010235
rattus_norvegicus	LOC134479283	ENSRNOG00000068283

Paralogs (2): PKIB (ENSG00000135549), PKIA (ENSG00000171033)

Protein

Protein identifiers

cAMP-dependent protein kinase inhibitor gamma — Q9Y2B9 (reviewed: Q9Y2B9)

All UniProt accessions (3): Q9Y2B9, Q549H9, Q5H937

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.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the PKI family.

RefSeq proteins (5): NP_001268373, NP_001268374, NP_008997, NP_861520, NP_861521 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004171	cAMP_dep_PKI	Family

Pfam: PF02827

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2B9-F1	63.28	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 266 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, LUCAS_HNF4A_TARGETS_UP, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, BOHN_PRIMARY_IMMUNODEFICIENCY_SYNDROM_DN, GOBP_NUCLEAR_TRANSPORT, MARTINEZ_RB1_TARGETS_UP, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, PAPASPYRIDONOS_UNSTABLE_ATEROSCLEROTIC_PLAQUE_DN, GOBP_REGULATION_OF_NUCLEOCYTOPLASMIC_TRANSPORT, MARTINEZ_RB1_TARGETS_DN, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_NEGATIVE_REGULATION_OF_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION, IRF1_Q6

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), negative regulation of protein import into nucleus (GO:0042308), 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
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
protein import into nucleus	1
regulation of protein import into nucleus	1
negative regulation of nucleocytoplasmic transport	1
negative regulation of intracellular protein transport	1
negative regulation of protein localization to nucleus	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

374 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PKIG	PKIA	P04541	982
PKIG	ADA	P00813	768
PKIG	PKIB	Q9C010	638
PKIG	FAM171B	Q6P995	428
PKIG	MRPS24	P82668	396
PKIG	PHF13	Q86YI8	393
PKIG	TTPAL	Q9BTX7	369
PKIG	ZSWIM2	Q8NEG5	336
PKIG	MCRIP2	Q9BUT9	329
PKIG	URAD	A6NGE7	313
PKIG	OSER1	Q9NX31	305
PKIG	PGCKA1	Q8IY42	305
PKIG	RIMS4	Q9H426	304
PKIG	RPP21	Q9H633	304
PKIG	CSTF1	Q05048	293

IntAct

16 interactions, top by confidence:

A	B	Type	Score
PRKACA	VAPB	psi-mi:“MI:0914”(association)	0.730
DYNLL2	PKIG	psi-mi:“MI:0915”(physical association)	0.560
DYNLL1	PKIG	psi-mi:“MI:0915”(physical association)	0.560
PKIG	TYMS	psi-mi:“MI:0914”(association)	0.530
PRKACB	MYL1	psi-mi:“MI:0914”(association)	0.350
PKIG	RPA3	psi-mi:“MI:0915”(physical association)	0.000
PKIG	KPTN	psi-mi:“MI:0915”(physical association)	0.000
PKIG	RAB25	psi-mi:“MI:0915”(physical association)	0.000
PKIG	PRKACA	psi-mi:“MI:0915”(physical association)	0.000
PKIG	DYNLL2	psi-mi:“MI:0915”(physical association)	0.000
PKIG	DYNLL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): PKIG (Two-hybrid), PRKACB (Affinity Capture-MS), TYMS (Affinity Capture-MS), TPM2 (Affinity Capture-MS), RAB25 (Affinity Capture-MS), KPTN (Affinity Capture-MS), RPA3 (Affinity Capture-MS), PRKACA (Affinity Capture-MS), PKIG (Two-hybrid), DYNLL2 (Two-hybrid), PRKACB (Affinity Capture-MS), PRKACG (Affinity Capture-MS), TYMS (Affinity Capture-MS), PKIG (Affinity Capture-MS), PKIG (Affinity Capture-MS)

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2194 predictions. Top by Δscore:

Variant	Effect	Δscore
20:44531978:GGTG:G	donor_loss	1.0000
20:44531979:GT:G	donor_loss	1.0000
20:44531980:T:A	donor_loss	1.0000
20:44589786:T:TA	acceptor_gain	1.0000
20:44589795:A:AG	acceptor_gain	1.0000
20:44589796:G:GG	acceptor_gain	1.0000
20:44589796:GA:G	acceptor_gain	1.0000
20:44614528:CCACA:C	acceptor_loss	1.0000
20:44614529:CACAG:C	acceptor_loss	1.0000
20:44614532:A:AG	acceptor_gain	1.0000
20:44614533:G:GG	acceptor_gain	1.0000
20:44614533:G:T	acceptor_loss	1.0000
20:44614533:GGC:G	acceptor_gain	1.0000
20:44614533:GGCCT:G	acceptor_gain	1.0000
20:44614638:G:GT	donor_gain	1.0000
20:44614649:GGCT:G	donor_gain	1.0000
20:44614650:GCTG:G	donor_gain	1.0000
20:44614657:GC:G	donor_gain	1.0000
20:44614664:G:GT	donor_gain	1.0000
20:44620412:C:CT	acceptor_gain	1.0000
20:44620427:CA:C	acceptor_gain	1.0000
20:44620428:A:AC	acceptor_gain	1.0000
20:44620428:A:C	acceptor_gain	1.0000
20:44620435:C:CT	acceptor_gain	1.0000
20:44620436:A:T	acceptor_gain	1.0000
20:44621014:TCA:T	donor_loss	1.0000
20:44621015:CA:C	donor_loss	1.0000
20:44621016:A:AC	donor_gain	1.0000
20:44621016:ACC:A	donor_loss	1.0000
20:44621016:ACCAG:A	donor_gain	1.0000

AlphaMissense

490 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:44614587:T:C	F11L	0.999
20:44614588:T:G	F11C	0.999
20:44614589:C:A	F11L	0.999
20:44614589:C:G	F11L	0.999
20:44614608:G:C	G18R	0.999
20:44614588:T:C	F11S	0.998
20:44614608:G:T	G18C	0.998
20:44614611:C:A	R19S	0.998
20:44614619:T:A	N21K	0.998
20:44614619:T:G	N21K	0.998
20:44614609:G:A	G18D	0.997
20:44614621:C:A	A22E	0.997
20:44614624:T:A	V23D	0.997
20:44614609:G:T	G18V	0.996
20:44614578:T:C	Y8H	0.995
20:44614591:T:A	I12N	0.995
20:44614615:G:C	R20P	0.995
20:44614617:A:G	N21D	0.995
20:44614618:A:T	N21I	0.995
20:44614603:G:C	R16P	0.994
20:44614611:C:G	R19G	0.992
20:44614612:G:C	R19P	0.992
20:44614620:G:C	A22P	0.992
20:44614578:T:G	Y8D	0.991
20:44614587:T:A	F11I	0.991
20:44614587:T:G	F11V	0.991
20:44614591:T:G	I12S	0.991
20:44614618:A:C	N21T	0.991
20:44614633:T:C	I26T	0.991
20:44614611:C:T	R19C	0.990

dbSNP variants (sampled 300 via entrez): RS1000033219 (20:44615259 A>C), RS1000059315 (20:44617354 G>A), RS1000088315 (20:44617077 C>T), RS1000101992 (20:44554845 G>C,T), RS1000137251 (20:44560333 C>T), RS1000194934 (20:44552535 A>G), RS1000236527 (20:44600557 A>G), RS1000262740 (20:44548643 C>A,T), RS1000286843 (20:44593705 A>G), RS1000330171 (20:44611370 TA>T), RS1000389787 (20:44604287 T>C), RS1000403430 (20:44558710 T>C), RS1000407073 (20:44571715 C>A), RS1000483486 (20:44586781 T>C), RS1000510595 (20:44572354 G>A,C)

Disease associations

OMIM: gene MIM:604932 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004131_41	Inflammatory bowel disease	1.000000e-17
GCST004133_4	Ulcerative colitis	4.000000e-30
GCST005434_24	Pancreatic cancer	5.000000e-06
GCST005537_54	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Cisplatin	affects expression, decreases expression	2
Valproic Acid	increases expression	2
Aflatoxin B1	affects expression, decreases expression	2
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression, increases abundance, affects cotreatment	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
Oxaliplatin	decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Acetaminophen	affects response to substance	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzene	decreases expression	1
Demecolcine	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Formaldehyde	increases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Methapyrilene	decreases methylation	1
Oligomycins	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases abundance, increases expression	1

Clinical trials (associated diseases)

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