GKAP1

Summary

GKAP1 (G kinase anchoring protein 1, HGNC:17496) is a protein-coding gene on chromosome 9q21.32, encoding G kinase-anchoring protein 1 (Q5VSY0). Regulates insulin-dependent IRS1 tyrosine phosphorylation in adipocytes by modulating the availability of IRS1 to IR tyrosine kinase.

This gene encodes a protein that is highly similar to the mouse cGMP-dependent protein kinase anchoring protein 42kDa. The mouse protein has been found to localize with the Golgi and recruit cGMP-dependent protein kinase I alpha to the Golgi in mouse testes. It is thought to play a role in germ cell development. Transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 80318 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_025211

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17496
Approved symbol	GKAP1
Name	G kinase anchoring protein 1
Location	9q21.32
Locus type	gene with protein product
Status	Approved
Aliases	GKAP42, FKSG21
Ensembl gene	ENSG00000165113
Ensembl biotype	protein_coding
OMIM	611356
Entrez	80318

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000376362, ENST00000376365, ENST00000376371, ENST00000388782, ENST00000462223, ENST00000485742, ENST00000491634, ENST00000889366, ENST00000962685, ENST00000962686, ENST00000962687, ENST00000962688, ENST00000962689, ENST00000962690, ENST00000962691, ENST00000962692, ENST00000962693, ENST00000962694, ENST00000962695

RefSeq mRNA: 2 — MANE Select: NM_025211 NM_001135953, NM_025211

CCDS: CCDS35049, CCDS47988

Canonical transcript exons

ENST00000376371 — 13 exons

Exon	Start	End
ENSE00001090466	83748309	83748372
ENSE00001090472	83799185	83799328
ENSE00001173712	83739425	83739744
ENSE00001289016	83817517	83817769
ENSE00001289038	83753258	83753359
ENSE00001289069	83816996	83817127
ENSE00001376113	83806302	83806560
ENSE00001503948	83768818	83768970
ENSE00003479598	83742530	83742600
ENSE00003554967	83741952	83742029
ENSE00003598667	83780382	83780404
ENSE00003599755	83788601	83788678
ENSE00003672866	83784715	83784838

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 99.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.5647 / max 82.5033, expressed in 1157 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101152	3.2071	1012
101153	1.2395	651
101151	0.0679	19
205537	0.0502	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.85	gold quality
secondary oocyte	CL:0000655	98.68	gold quality
left testis	UBERON:0004533	98.57	gold quality
right testis	UBERON:0004534	98.38	gold quality
adult organism	UBERON:0007023	97.83	gold quality
testis	UBERON:0000473	97.11	gold quality
vastus lateralis	UBERON:0001379	96.39	gold quality
quadriceps femoris	UBERON:0001377	96.16	gold quality
biceps brachii	UBERON:0001507	95.44	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.24	gold quality
deltoid	UBERON:0001476	94.76	gold quality
skeletal muscle tissue	UBERON:0001134	94.74	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.36	gold quality
oocyte	CL:0000023	94.04	gold quality
tibialis anterior	UBERON:0001385	93.52	gold quality
gastrocnemius	UBERON:0001388	93.29	gold quality
muscle tissue	UBERON:0002385	93.14	gold quality
buccal mucosa cell	CL:0002336	93.06	gold quality
muscle of leg	UBERON:0001383	92.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.52	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.37	gold quality
epithelial cell of pancreas	CL:0000083	92.12	gold quality
left ventricle myocardium	UBERON:0006566	91.96	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.91	gold quality
ventricular zone	UBERON:0003053	90.14	gold quality
medial globus pallidus	UBERON:0002477	89.86	gold quality
heart right ventricle	UBERON:0002080	89.41	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.33	silver quality
calcaneal tendon	UBERON:0003701	88.94	gold quality
globus pallidus	UBERON:0001875	88.86	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	512.52
E-GEOD-134144	yes	30.43
E-ANND-3	yes	4.89

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT3

miRNA regulators (miRDB)

57 targeting GKAP1, 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-6077	99.99	68.04	2299
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085

Literature-anchored findings (GeneRIF, showing 1)

• This paper describes the protein interaction, expression, localization and function of a highly similar gene in mouse. (PMID:10671526)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gkap1	ENSDARG00000068123
mus_musculus	Gkap1	ENSMUSG00000021552
rattus_norvegicus	Gkap1	ENSRNOG00000019272

Protein

Protein identifiers

G kinase-anchoring protein 1 — Q5VSY0 (reviewed: Q5VSY0)

Alternative names: cGMP-dependent protein kinase-anchoring protein of 42 kDa

All UniProt accessions (3): B4DXS0, C9J9D2, Q5VSY0

UniProt curated annotations — full annotation on UniProt →

Function. Regulates insulin-dependent IRS1 tyrosine phosphorylation in adipocytes by modulating the availability of IRS1 to IR tyrosine kinase. Its association with IRS1 is required for insulin-induced translocation of SLC2A4 to the cell membrane. Involved in TNF-induced impairment of insulin-dependent IRS1 tyrosine phosphorylation.

Subunit / interactions. Interacts with PRKG1 and IRS1.

Subcellular location. Golgi apparatus.

Similarity. Belongs to the GKAP1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VSY0-1	1	yes
Q5VSY0-2	2

RefSeq proteins (2): NP_001129425, NP_079487* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026109	GKAP1	Family

UniProt features (14 total): modified residue 4, region of interest 3, coiled-coil region 3, chain 1, splice variant 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VSY0-F1	72.22	0.42

Functional residue map

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

Post-translational modifications (4): 27, 106, 23, 25

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 157 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BENPORATH_ES_WITH_H3K27ME3, PEREZ_TP63_TARGETS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_RESPONSE_TO_INSULIN, BILD_E2F3_ONCOGENIC_SIGNATURE, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POSITIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_HORMONE

GO Biological Process (3): signal transduction (GO:0007165), obsolete cGMP-mediated signaling (GO:0019934), positive regulation of insulin receptor signaling pathway (GO:0046628)

GO Molecular Function (3): identical protein binding (GO:0042802), protein binding (GO:0005515), kinase activity (GO:0016301)

GO Cellular Component (1): Golgi apparatus (GO:0005794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
insulin receptor signaling pathway	1
positive regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
positive regulation of cellular response to insulin stimulus	1
protein binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GKAP1	PRKG1	P14619	875
GKAP1	KIF27	Q86VH2	579
GKAP1	ITGA2B	P08514	549
GKAP1	QNG1	Q5T6V5	526
GKAP1	TSACC	Q96A04	522
GKAP1	C22orf23	Q9BZE7	507
GKAP1	VWF	P04275	496
GKAP1	IRS1	P35568	495
GKAP1	CATSPERT	Q53TS8	479
GKAP1	ACTRT2	Q8TDY3	447
GKAP1	CD34	P28906	423
GKAP1	ODAD4	Q96NG3	410
GKAP1	TMEM229A	B2RXF0	399
GKAP1	CCDC54	Q8NEL0	398
GKAP1	GARIN1B	Q96KD3	391

IntAct

76 interactions, top by confidence:

A	B	Type	Score
GKAP1	GKAP1	psi-mi:“MI:0915”(physical association)	0.670
DYR	GKAP1	psi-mi:“MI:0915”(physical association)	0.560
GKAP1	MFAP1	psi-mi:“MI:0915”(physical association)	0.560
GKAP1	HDDC3	psi-mi:“MI:0915”(physical association)	0.560
GKAP1	DYR	psi-mi:“MI:0915”(physical association)	0.560
MFAP1	GKAP1	psi-mi:“MI:0915”(physical association)	0.560
HDDC3	GKAP1	psi-mi:“MI:0915”(physical association)	0.560
GKAP1	GCD7	psi-mi:“MI:0915”(physical association)	0.560
GKAP1	PSH1	psi-mi:“MI:0915”(physical association)	0.560
PSH1	GKAP1	psi-mi:“MI:0915”(physical association)	0.560
GCD7	GKAP1	psi-mi:“MI:0915”(physical association)	0.560
	GKAP1	psi-mi:“MI:0915”(physical association)	0.560
GKAP1	ZCCHC10	psi-mi:“MI:0915”(physical association)	0.560
GKAP1	L3MBTL2	psi-mi:“MI:0915”(physical association)	0.560
GKAP1	PHOSPHO2	psi-mi:“MI:0915”(physical association)	0.560
GKAP1	KANK2	psi-mi:“MI:0915”(physical association)	0.560
GKAP1	KAT5	psi-mi:“MI:0915”(physical association)	0.560
GKAP1	RCOR3	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	GKAP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (61): GKAP1 (Two-hybrid), GKAP1 (Two-hybrid), GKAP1 (Two-hybrid), HDDC3 (Two-hybrid), GKAP1 (Two-hybrid), GKAP1 (Two-hybrid), GKAP1 (Affinity Capture-MS), GKAP1 (Proximity Label-MS), GKAP1 (Affinity Capture-MS), GKAP1 (Affinity Capture-MS), GKAP1 (Affinity Capture-MS), GKAP1 (Affinity Capture-MS), GKAP1 (Affinity Capture-MS), GKAP1 (Affinity Capture-MS), GKAP1 (Affinity Capture-MS)

ESM2 similar proteins: A4PB26, D3ZTQ1, G1SW77, O16053, O88271, Q12872, Q32LE2, Q3MHS2, Q3U155, Q3USH5, Q4ADK4, Q4ADK7, Q4VAA2, Q5M8L3, Q5PQP2, Q5PQS7, Q5RKH3, Q5VSY0, Q5XHI2, Q5XIG5, Q5XIM5, Q5ZLH9, Q60FC2, Q63ZM9, Q6AXS5, Q6DIS2, Q6DJ13, Q6GNQ4, Q6NWC9, Q6PFK1, Q75UQ2, Q7T370, Q7ZYA6, Q8HXY9, Q8K039, Q8MMC4, Q8NC51, Q8R1N0, Q92733, Q96NB3

Diamond homologs: Q32LE2, Q5M8L3, Q5VSY0, Q5XIG5, Q6GNQ4, Q6NWC9, Q8AVX1, Q9JMB0

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	GKAP1	polyubiquitination
PRKG1	unknown	GKAP1	phosphorylation
TRIM3	“down-regulates quantity by destabilization”	GKAP1	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2386 predictions. Top by Δscore:

Variant	Effect	Δscore
9:83742601:C:CC	acceptor_gain	1.0000
9:83748307:A:AC	donor_gain	1.0000
9:83748308:C:CC	donor_gain	1.0000
9:83753259:T:TA	donor_gain	1.0000
9:83753260:C:A	donor_gain	1.0000
9:83753305:T:A	donor_gain	1.0000
9:83753356:CTTC:C	acceptor_gain	1.0000
9:83753357:TTC:T	acceptor_gain	1.0000
9:83753358:TC:T	acceptor_gain	1.0000
9:83753359:CC:C	acceptor_gain	1.0000
9:83753360:C:CC	acceptor_gain	1.0000
9:83753360:C:CG	acceptor_loss	1.0000
9:83784710:ATTAC:A	donor_loss	1.0000
9:83784711:TTA:T	donor_loss	1.0000
9:83784712:TA:T	donor_loss	1.0000
9:83784713:A:AT	donor_loss	1.0000
9:83784714:C:CG	donor_loss	1.0000
9:83784717:T:A	donor_gain	1.0000
9:83784834:TACTC:T	acceptor_gain	1.0000
9:83784836:CTC:C	acceptor_gain	1.0000
9:83784837:TC:T	acceptor_gain	1.0000
9:83784838:CC:C	acceptor_gain	1.0000
9:83784838:CCTAA:C	acceptor_loss	1.0000
9:83784839:C:A	acceptor_loss	1.0000
9:83784839:C:CC	acceptor_gain	1.0000
9:83784840:T:G	acceptor_loss	1.0000
9:83788679:C:CC	acceptor_gain	1.0000
9:83799173:A:AC	donor_gain	1.0000
9:83799174:C:CC	donor_gain	1.0000
9:83799177:A:AC	donor_gain	1.0000

AlphaMissense

2413 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:83742540:A:G	L322P	1.000
9:83742011:C:G	A332P	0.999
9:83742019:A:G	L329P	0.999
9:83742589:C:G	A306P	0.999
9:83788650:A:G	L130P	0.999
9:83799205:A:G	W114R	0.999
9:83799205:A:T	W114R	0.999
9:83799311:A:C	F78L	0.999
9:83799311:A:T	F78L	0.999
9:83799313:A:G	F78L	0.999
9:83799315:G:T	A77D	0.999
9:83806470:A:C	F16L	0.999
9:83806470:A:T	F16L	0.999
9:83806471:A:G	F16S	0.999
9:83806472:A:G	F16L	0.999
9:83741993:A:G	S338P	0.998
9:83742579:A:G	L309P	0.998
9:83748323:A:G	L297P	0.998
9:83748335:A:G	L293S	0.998
9:83788642:C:G	A133P	0.998
9:83799203:C:A	W114C	0.998
9:83799203:C:G	W114C	0.998
9:83799327:A:G	L73P	0.998
9:83799327:A:T	L73H	0.998
9:83806462:A:G	L19S	0.998
9:83742540:A:T	L322H	0.997
9:83748346:T:A	R289S	0.997
9:83748346:T:G	R289S	0.997
9:83788628:A:C	S137R	0.997
9:83788628:A:T	S137R	0.997

dbSNP variants (sampled 300 via entrez): RS1000001796 (9:83818111 C>T), RS1000019476 (9:83793571 A>G), RS1000019521 (9:83791912 G>C), RS1000110095 (9:83812977 CT>C,CTT), RS1000131124 (9:83755248 A>G), RS1000171899 (9:83746751 A>C), RS1000181281 (9:83743216 T>C,G), RS1000191189 (9:83758086 T>TTG), RS1000224863 (9:83754954 G>A,T), RS1000272735 (9:83795230 T>A), RS1000303295 (9:83802851 G>C), RS1000332493 (9:83739219 T>C), RS1000337957 (9:83761323 A>G), RS1000348070 (9:83783371 C>A,G), RS1000356698 (9:83803103 C>A)

Disease associations

OMIM: gene MIM:611356 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004600_77	Eosinophil percentage of white cells	9.000000e-12
GCST004617_168	Eosinophil percentage of granulocytes	8.000000e-12
GCST004623_124	Neutrophil percentage of granulocytes	6.000000e-11
GCST007576_54	Chronotype	2.000000e-10
GCST010173_69	Triglyceride levels	3.000000e-14
GCST011494_48	Daytime nap	3.000000e-11
GCST90000047_197	Age at first sexual intercourse	2.000000e-09
GCST90002381_476	Eosinophil count	5.000000e-17

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0008328	chronotype measurement
EFO:0004530	triglyceride measurement
EFO:0007828	daytime rest measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0004842	eosinophil count

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
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation, increases expression	9
trichostatin A	affects cotreatment, decreases expression, increases expression	3
sodium arsenite	affects expression, decreases expression, increases expression	3
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Nickel	decreases expression	2
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
deoxynivalenol	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
MT19c compound	increases expression	1
Bortezomib	increases expression	1
Acetaminophen	increases expression	1
Amiodarone	increases expression	1
Cisplatin	decreases expression, affects cotreatment	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Theophylline	increases expression	1
Tretinoin	decreases expression	1

Clinical trials (associated diseases)

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