AKAP19

Summary

AKAP19 (A-kinase anchoring protein 19, HGNC:28191) is a protein-coding gene on chromosome 2q32.2, encoding A-kinase anchoring protein 19 (Q9BSF0). Binds to type I regulatory subunits of protein kinase A (PKA-RI) and anchors/targets them to the plasma membrane.

Predicted to enable protein kinase A regulatory subunit binding activity. Predicted to be located in plasma membrane.

Source: NCBI Gene 84281 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 92 total — 2 pathogenic
• MANE Select transcript: NM_001042519

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28191
Approved symbol	AKAP19
Name	A-kinase anchoring protein 19
Location	2q32.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC13057, smAKAP
Ensembl gene	ENSG00000187699
Ensembl biotype	protein_coding
OMIM	615117
Entrez	84281

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000340623, ENST00000396974, ENST00000409545, ENST00000409870, ENST00000443551, ENST00000450357, ENST00000478197, ENST00000490033, ENST00000495546, ENST00000870652, ENST00000870653, ENST00000870654, ENST00000870655, ENST00000917871, ENST00000917872, ENST00000948384, ENST00000948385

RefSeq mRNA: 4 — MANE Select: NM_001042519 NM_001042519, NM_001042520, NM_001042521, NM_032321

CCDS: CCDS42792

Canonical transcript exons

ENST00000340623 — 2 exons

Exon	Start	End
ENSE00000934448	190199697	190203484
ENSE00001416737	190180863	190181109

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 97.29.

FANTOM5 (CAGE): breadth broad, TPM avg 7.2893 / max 297.3591, expressed in 717 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24269	3.5287	577
24267	2.5515	303
24272	0.6444	226
24270	0.3854	163
24268	0.1068	50
24266	0.0418	3
24271	0.0229	10
24263	0.0078	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	97.29	gold quality
sperm	CL:0000019	97.19	gold quality
left testis	UBERON:0004533	95.86	gold quality
right testis	UBERON:0004534	95.46	gold quality
monocyte	CL:0000576	94.75	gold quality
jejunal mucosa	UBERON:0000399	94.70	gold quality
mucosa of transverse colon	UBERON:0004991	94.16	gold quality
leukocyte	CL:0000738	93.68	gold quality
testis	UBERON:0000473	93.38	gold quality
endometrium	UBERON:0001295	93.25	gold quality
rectum	UBERON:0001052	93.09	gold quality
duodenum	UBERON:0002114	90.91	gold quality
colonic mucosa	UBERON:0000317	90.10	gold quality
left ventricle myocardium	UBERON:0006566	89.34	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.59	gold quality
transverse colon	UBERON:0001157	88.01	gold quality
right uterine tube	UBERON:0001302	87.96	gold quality
tibial nerve	UBERON:0001323	87.56	gold quality
oviduct epithelium	UBERON:0004804	87.52	gold quality
parotid gland	UBERON:0001831	87.00	gold quality
dorsal root ganglion	UBERON:0000044	86.40	gold quality
endocervix	UBERON:0000458	86.26	gold quality
oocyte	CL:0000023	86.19	gold quality
bone marrow cell	CL:0002092	86.15	gold quality
small intestine	UBERON:0002108	86.06	gold quality
tibialis anterior	UBERON:0001385	85.91	gold quality
cardiac muscle of right atrium	UBERON:0003379	85.90	gold quality
corpus callosum	UBERON:0002336	85.55	gold quality
myocardium	UBERON:0002349	85.35	gold quality
jejunum	UBERON:0002115	85.26	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-MTAB-10283	yes	546.45
E-ANND-5	yes	511.75
E-MTAB-10287	yes	51.02
E-CURD-112	yes	39.18
E-HCAD-4	yes	29.51
E-GEOD-125970	yes	27.02
E-HCAD-6	yes	23.41
E-CURD-122	yes	22.57
E-MTAB-9221	yes	18.27
E-HCAD-10	yes	17.36
E-MTAB-9067	yes	12.17
E-HCAD-1	yes	5.16
E-MTAB-9801	no	2.84
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

164 targeting AKAP19, 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-340-5P	100.00	72.50	4437
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-218-5P	99.93	72.22	2103
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-338-5P	99.92	72.34	2951
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-124-3P	99.89	73.74	3043

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	1700019D03Rik	ENSMUSG00000043629
rattus_norvegicus	C9h2orf88	ENSRNOG00000038738

Protein

Protein identifiers

A-kinase anchoring protein 19 — Q9BSF0 (reviewed: Q9BSF0)

Alternative names: Small membrane A-kinase anchor protein

All UniProt accessions (3): C9JS57, Q9BSF0, H7BZ15

UniProt curated annotations — full annotation on UniProt →

Function. Binds to type I regulatory subunits of protein kinase A (PKA-RI) and anchors/targets them to the plasma membrane.

Subunit / interactions. Interacts with PKA type I regulatory subunits PRKAR1A and PRKAR1B; this interaction targets PRKAR1A and PRKAR1B to the plasma membrane. Also binds to type II regulatory subunits, but at a tenfold lower affinity.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in heart (at protein level).

Post-translational modifications. Phosphorylation at Ser-66 by PKA disrupts interaction with PRKAR1A and PRKAR1B, resulting in loss of their plasma membrane localization. May be palmitoylated at Cys-3.

Similarity. Belongs to the small membrane AKAP family.

RefSeq proteins (4): NP_001035984, NP_001035985, NP_001035986, NP_115697 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027969	Small_membr_AKAP	Family

Pfam: PF15127

UniProt features (15 total): mutagenesis site 4, modified residue 3, lipid moiety-binding region 2, initiator methionine 1, chain 1, sequence conflict 1, helix 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5HVZ	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSF0-F1	71.22	0.29

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 (5): 40, 66, 92, 2, 3

Mutagenesis-validated functional residues (4):

Position	Phenotype
3	loss of plasma membrane localization.
66	phosphomimetic mutant. abolishes interaction with prkar1a and prkar1b resulting in the loss of their plasma membrane loc
2	loss of plasma membrane localization.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 115 (showing top): SABATES_COLORECTAL_ADENOMA_DN, BASAKI_YBX1_TARGETS_DN, GRADE_COLON_AND_RECTAL_CANCER_DN, GOMF_PROTEIN_KINASE_A_REGULATORY_SUBUNIT_BINDING, GOMF_PROTEIN_KINASE_A_BINDING, GOTTWEIN_TARGETS_OF_KSHV_MIR_K12_11, LIU_PROSTATE_CANCER_DN, MEISSNER_NPC_HCP_WITH_H3K4ME2, TIAN_BHLHA15_TARGETS, RAO_BOUND_BY_SALL4, LIM_MAMMARY_LUMINAL_MATURE_DN, GSE5503_MLN_DC_VS_PLN_DC_ACTIVATED_ALLOGENIC_TCELL_DN, GSE14699_NAIVE_VS_DELETIONAL_TOLERANCE_CD8_TCELL_DN, GSE5503_PLN_DC_VS_SPLEEN_DC_ACTIVATED_ALLOGENIC_TCELL_DN, DLX6_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase A binding	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

27 interactions, top by confidence:

A	B	Type	Score
C2orf88	PRKAR1A	psi-mi:“MI:0915”(physical association)	0.740
PRKAR1A	C2orf88	psi-mi:“MI:0915”(physical association)	0.740
PRKACA	VAPB	psi-mi:“MI:0914”(association)	0.730
ZMIZ2	C2orf88	psi-mi:“MI:0915”(physical association)	0.560
C2orf88	ZMIZ2	psi-mi:“MI:0915”(physical association)	0.560
CENPP	C2orf88	psi-mi:“MI:0915”(physical association)	0.560
PRKAR2B	C2orf88	psi-mi:“MI:0915”(physical association)	0.560
MYOD1	C2orf88	psi-mi:“MI:0915”(physical association)	0.370
NFKBIL1	C2orf88	psi-mi:“MI:0915”(physical association)	0.370
C2orf88	RALGPS1	psi-mi:“MI:0915”(physical association)	0.370
TDP2	C2orf88	psi-mi:“MI:0915”(physical association)	0.370
ARMC7	C2orf88	psi-mi:“MI:0915”(physical association)	0.370
C2orf88	BATF2	psi-mi:“MI:0915”(physical association)	0.370
PRKACB	MYL1	psi-mi:“MI:0914”(association)	0.350
PRKAR1A	C2orf88	psi-mi:“MI:0915”(physical association)	0.000
CENPP	C2orf88	psi-mi:“MI:0915”(physical association)	0.000
PRKAR2B	C2orf88	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): C2orf88 (Two-hybrid), C2orf88 (Two-hybrid), C2orf88 (Affinity Capture-RNA), C2orf88 (Biochemical Activity), C2orf88 (Two-hybrid), C2orf88 (Two-hybrid), CENPP (Two-hybrid), C2orf88 (Affinity Capture-MS), C2orf88 (Affinity Capture-RNA), C2orf88 (Affinity Capture-MS), C2orf88 (Affinity Capture-RNA), RALGPS1 (Two-hybrid), TDP2 (Two-hybrid), NFKBIL1 (Two-hybrid), MYOD1 (Two-hybrid)

ESM2 similar proteins: A7E1Z1, A7J1T2, A7MB05, A7MBB4, A8MZ97, B8PYG1, E1BLT8, E9QDC5, F1QPR4, F5HGU6, M0R5D6, O01700, O15021, O43283, P03177, P0CAX8, P18345, P25049, P60571, P69338, P69339, Q1HVD1, Q2THW7, Q2THW9, Q2THX1, Q3KSQ2, Q3TEL6, Q3U5C7, Q3ZBS1, Q5R7R7, Q5R838, Q5R8X7, Q66624, Q68D42, Q6IMP4, Q6X4W1, Q71QF9, Q811L6, Q8BQU7, Q8VDZ4

Diamond homologs: P0C8S0, P0C8Y6, P0C8Y7, Q3SZY8, Q4RTJ5, Q9BSF0, Q9CPS8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	56
Likely benign	8
Benign	21

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
4682545	GRCh37/hg19 2q31.3-33.1(chr2:181362315-202911548)x1	Pathogenic
7705	NM_005259.3(MSTN):c.373+5G>A	Pathogenic

SpliceAI

1139 predictions. Top by Δscore:

Variant	Effect	Δscore
2:190062221:TA:T	donor_loss	1.0000
2:190062222:A:AC	donor_gain	1.0000
2:190062222:A:T	donor_loss	1.0000
2:190062222:ACACT:A	donor_gain	1.0000
2:190062223:C:CC	donor_gain	1.0000
2:190062223:CA:C	donor_gain	1.0000
2:190062223:CACT:C	donor_gain	1.0000
2:190062223:CACTC:C	donor_gain	1.0000
2:190057637:TT:T	acceptor_gain	0.9900
2:190060055:CACTT:C	donor_loss	0.9900
2:190060056:ACTTA:A	donor_loss	0.9900
2:190060057:CTT:C	donor_loss	0.9900
2:190060058:TTA:T	donor_loss	0.9900
2:190060059:TACCA:T	donor_loss	0.9900
2:190060060:A:T	donor_loss	0.9900
2:190060061:C:CT	donor_loss	0.9900
2:190060433:CAG:C	acceptor_gain	0.9900
2:190061303:G:A	donor_gain	0.9900
2:190062216:CTACT:C	donor_loss	0.9900
2:190062217:TACTT:T	donor_loss	0.9900
2:190062218:ACTTA:A	donor_loss	0.9900
2:190057638:TC:T	acceptor_loss	0.9800
2:190057639:C:CC	acceptor_gain	0.9800
2:190057639:C:CG	acceptor_loss	0.9800
2:190057640:T:C	acceptor_loss	0.9800
2:190060060:A:AC	donor_gain	0.9800
2:190060060:ACCAG:A	donor_gain	0.9800
2:190060061:C:CC	donor_gain	0.9800
2:190060061:CCAGC:C	donor_gain	0.9800
2:190062220:TTA:T	donor_gain	0.9800

AlphaMissense

635 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:190200054:T:C	L65P	0.983
2:190200077:G:C	A73P	0.979
2:190200089:T:A	W77R	0.977
2:190200089:T:C	W77R	0.977
2:190200056:T:C	S66P	0.971
2:190200091:G:C	W77C	0.970
2:190200091:G:T	W77C	0.970
2:190199875:A:C	K5N	0.968
2:190199875:A:T	K5N	0.968
2:190200066:T:C	I69T	0.965
2:190199864:G:C	G2R	0.961
2:190200045:C:A	A62E	0.961
2:190200044:G:C	A62P	0.960
2:190200066:T:G	I69S	0.957
2:190200078:C:A	A73D	0.955
2:190199881:G:C	K7N	0.951
2:190199881:G:T	K7N	0.951
2:190199874:A:T	K5I	0.939
2:190200120:T:G	I87S	0.938
2:190199873:A:G	K5E	0.935
2:190200120:T:C	I87T	0.935
2:190199865:G:A	G2D	0.934
2:190200066:T:A	I69N	0.932
2:190200042:A:C	Y61S	0.922
2:190200087:A:C	Q76P	0.922
2:190199874:A:C	K5T	0.921
2:190200090:G:C	W77S	0.913
2:190200111:A:C	Y84S	0.913
2:190200129:T:A	I90N	0.912
2:190200057:C:T	S66F	0.907

dbSNP variants (sampled 300 via entrez): RS1000008946 (2:190089289 A>C,G), RS1000016423 (2:190046074 C>T), RS1000017826 (2:190071421 T>A), RS1000042889 (2:190177195 T>G), RS1000043275 (2:190004190 G>A,T), RS1000044310 (2:190189867 G>A), RS1000048112 (2:189961017 G>A,C,T), RS1000061712 (2:190016698 G>A), RS1000072483 (2:189974936 T>C), RS1000074366 (2:190004431 G>A,C,T), RS1000078729 (2:190195293 C>T), RS1000084914 (2:190070903 A>G), RS1000093490 (2:190176810 T>C,G), RS1000102012 (2:190089055 T>C), RS1000110862 (2:189985064 G>A)

Disease associations

OMIM: gene MIM:615117 | disease phenotypes: MIM:614160

GenCC curated gene-disease

Mondo (1): myostatin-related muscle hypertrophy (MONDO:0013598)

Orphanet (1): OBSOLETE: Myostatin-related muscle hypertrophy (Orphanet:275534)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003518_96	Daytime sleep phenotypes	5.000000e-06
GCST012309_7	Schizophrenia	9.000000e-06
GCST90002385_455	High light scatter reticulocyte count	3.000000e-11
GCST90002386_269	High light scatter reticulocyte percentage of red cells	1.000000e-11
GCST90002405_143	Reticulocyte count	3.000000e-09
GCST90002406_62	Reticulocyte fraction of red cells	3.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536106	Myostatin-related muscle hypertrophy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenite	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Benzene	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Gallic Acid	increases expression	1
Silicon Dioxide	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
beta-Naphthoflavone	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03991117	Not specified	COMPLETED	Lower and Higher Load Resistance Exercise Protocols: Acute Muscle Activation and Skeletal Muscle Hypertrophy
NCT03993483	Not specified	COMPLETED	Upper Versus Lower Limb Responses to Higher Versus Lower Load Resistance Training in Young Men
NCT04000750	Not specified	COMPLETED	Time-Restricted Eating and Muscle Hypertrophy
NCT06666127	Not specified	ENROLLING_BY_INVITATION	The Effect of Peak Force At Long and Short Muscle Lengths and the Impact on Muscle Growth and Strength
NCT06698055	Not specified	COMPLETED	Muscle Adaptations in Children and Adults Following Twelve Weeks of Flywheel or Weight Stack Resistance Exercise
NCT06718712	Not specified	COMPLETED	Resistance Exercise Volume and Hypertrophic Response Variability in Elderly
NCT06760663	Not specified	COMPLETED	The Load-velocity Relationship: Neuromuscular Adaptations to Resistance Training
NCT06912867	Not specified	COMPLETED	Effects of BFR Training on Muscle Strength, Thickness, and Motivation in National Adolescent Male Canoe Athletes
NCT07171411	Not specified	COMPLETED	Combined Whey Protein and Collagen Supplementation in Resistance-Trained Men
NCT07360236	Not specified	NOT_YET_RECRUITING	Determining the Effect of Shoulder Flexion Angle on Latissimus Dorsi and Forearm Flexor Hypertrophy
NCT07412600	Not specified	COMPLETED	High- and Low-Load Resistance Training
NCT07561281	Not specified	COMPLETED	Low-Load BFR vs. High-Load Training on Biceps Hypertrophy
NCT07600138	Not specified	COMPLETED	Effects of Carbohydrates Versus Carbohydrates + Protein on Resistance Training Outcomes