FKBP2

Summary

FKBP2 (FKBP prolyl isomerase 2, HGNC:3718) is a protein-coding gene on chromosome 11q13.1, encoding Peptidyl-prolyl cis-trans isomerase FKBP2 (P26885). PPIases accelerate the folding of proteins.

The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 and rapamycin. It is thought to function as an ER chaperone and may also act as a component of membrane cytoskeletal scaffolds. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 2286 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 20 total
• Druggable target: yes
• MANE Select transcript: NM_004470

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3718
Approved symbol	FKBP2
Name	FKBP prolyl isomerase 2
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	FKBP-13, FKBP13, PPIase
Ensembl gene	ENSG00000173486
Ensembl biotype	protein_coding
OMIM	186946
Entrez	2286

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 retained_intron

ENST00000309366, ENST00000449942, ENST00000535135, ENST00000536642, ENST00000541388, ENST00000652094

RefSeq mRNA: 8 — MANE Select: NM_004470 NM_001135208, NM_001370360, NM_001370362, NM_001370363, NM_001370365, NM_001370367, NM_004470, NM_057092

CCDS: CCDS8063, CCDS91499

Canonical transcript exons

ENST00000309366 — 6 exons

Exon	Start	End
ENSE00001195893	64243451	64243497
ENSE00001380157	64243968	64244132
ENSE00002319473	64241095	64241132
ENSE00003460987	64243199	64243311
ENSE00003484707	64242384	64242558
ENSE00003499073	64243841	64243876

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.4240 / max 1684.1445, expressed in 1825 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114903	54.5989	1823
114905	8.7057	1795
114901	5.0242	1635
114902	1.0639	738
114906	0.6966	441
114900	0.5597	322
114904	0.3642	159
114907	0.2071	87
114899	0.1779	96
114898	0.0259	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	99.21	gold quality
adenohypophysis	UBERON:0002196	99.16	gold quality
body of pancreas	UBERON:0001150	98.87	gold quality
right lobe of thyroid gland	UBERON:0001119	98.86	gold quality
left lobe of thyroid gland	UBERON:0001120	98.66	gold quality
thyroid gland	UBERON:0002046	98.53	gold quality
mucosa of transverse colon	UBERON:0004991	98.53	gold quality
right lobe of liver	UBERON:0001114	98.41	gold quality
pancreas	UBERON:0001264	98.39	gold quality
primary visual cortex	UBERON:0002436	98.37	gold quality
hypothalamus	UBERON:0001898	98.34	gold quality
adult mammalian kidney	UBERON:0000082	98.31	gold quality
substantia nigra	UBERON:0002038	98.31	gold quality
cortex of kidney	UBERON:0001225	98.23	gold quality
putamen	UBERON:0001874	98.18	gold quality
duodenum	UBERON:0002114	98.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.13	gold quality
endocervix	UBERON:0000458	98.06	gold quality
right adrenal gland	UBERON:0001233	98.03	gold quality
caudate nucleus	UBERON:0001873	98.03	gold quality
prefrontal cortex	UBERON:0000451	98.02	gold quality
left adrenal gland	UBERON:0001234	98.02	gold quality
left adrenal gland cortex	UBERON:0035825	98.01	gold quality
nucleus accumbens	UBERON:0001882	97.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.90	gold quality
Ammon’s horn	UBERON:0001954	97.84	gold quality
prostate gland	UBERON:0002367	97.84	gold quality
metanephros cortex	UBERON:0010533	97.84	gold quality
liver	UBERON:0002107	97.82	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	124.63
E-CURD-46	yes	82.89
E-HCAD-1	yes	75.10
E-HCAD-4	yes	73.36
E-MTAB-9467	yes	61.90
E-CURD-122	yes	54.00
E-MTAB-8410	yes	43.20
E-ANND-3	yes	33.79
E-MTAB-5061	yes	25.80
E-HCAD-11	yes	21.33
E-MTAB-6701	yes	15.11
E-CURD-112	yes	13.30
E-MTAB-10553	yes	11.50
E-MTAB-9543	yes	10.81
E-MTAB-6678	yes	8.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting FKBP2, 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-8068	99.98	73.85	2376
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-129-5P	99.88	70.26	3273

Literature-anchored findings (GeneRIF, showing 2)

• FKBP13 and FK506 have roles in vesicular trafficking, influencing ADP-ribosylation factor activity through their guanine nucleotide-exchange proteins (PMID:12606707)
• observed changes in activity of six rER-resident PPIases, cyclophilin B (encoded by the PPIB gene), FKBP13 (FKBP2), FKBP19 (FKBP11), FKBP22 (FKBP14), FKBP23 (FKBP7), and FKBP65 (FKBP10), due to posttranslational modifications of proline residues in the substrate. (PMID:28385890)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fkbp2	ENSDARG00000044540
mus_musculus	Fkbp2	ENSMUSG00000056629
rattus_norvegicus	Fkbp2	ENSRNOG00000021153
drosophila_melanogaster	CG14715	FBGN0037930
caenorhabditis_elegans		WBGENE00001426

Paralogs (18): FKBP4 (ENSG00000004478), FKBP6 (ENSG00000077800), FKBP7 (ENSG00000079150), FKBP1A (ENSG00000088832), FKBP5 (ENSG00000096060), FKBP3 (ENSG00000100442), FKBP8 (ENSG00000105701), FKBP14 (ENSG00000106080), FKBP15 (ENSG00000119321), FKBP1B (ENSG00000119782), FKBP9 (ENSG00000122642), TTC9 (ENSG00000133985), FKBP11 (ENSG00000134285), FKBP10 (ENSG00000141756), TTC9C (ENSG00000162222), TTC9B (ENSG00000174521), FKBP1C (ENSG00000198225), FKBPL (ENSG00000204315)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase FKBP2 — P26885 (reviewed: P26885)

Alternative names: 13 kDa FK506-binding protein, FK506-binding protein 2, Immunophilin FKBP13, Rotamase

All UniProt accessions (4): P26885, A0A494C1N0, F5H0N4, Q53XJ5

UniProt curated annotations — full annotation on UniProt →

Function. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.

Subunit / interactions. Interacts with ARFGEF1/BIG1 and the C-terminal of EPB41L2.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. T-cells and thymus.

Activity regulation. Inhibited by both FK506 and rapamycin.

Similarity. Belongs to the FKBP-type PPIase family. FKBP2 subfamily.

RefSeq proteins (8): NP_001128680, NP_001357289, NP_001357291, NP_001357292, NP_001357294, NP_001357296, NP_004461, NP_476433 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001179	PPIase_FKBP_dom	Domain
IPR044609	FKBP2/11	Family
IPR046357	PPIase_dom_sf	Homologous_superfamily

Pfam: PF00254

Catalyzed reactions (Rhea), 1 shown:

• [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0) (RHEA:16237)

UniProt features (20 total): strand 6, sequence variant 4, turn 3, helix 3, signal peptide 1, chain 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2PBC	X-RAY DIFFRACTION	1.8
4NNR	X-RAY DIFFRACTION	1.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26885-F1	89.67	0.77

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 203 (showing top): GGGACCA_MIR133A_MIR133B, MYAATNNNNNNNGGC_UNKNOWN, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GRUETZMANN_PANCREATIC_CANCER_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCGCANK_UNKNOWN, SWEET_KRAS_ONCOGENIC_SIGNATURE, MODULE_151, LFA1_Q6, ENK_UV_RESPONSE_KERATINOCYTE_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MAZ_Q6, chr11q13, CEBP_Q2, GATA3_01

GO Biological Process (2): protein peptidyl-prolyl isomerization (GO:0000413), obsolete chaperone-mediated protein folding (GO:0061077)

GO Molecular Function (4): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), FK506 binding (GO:0005528), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptidyl-proline modification	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
macrolide binding	1
binding	1
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2123 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FKBP2	PLCB3	Q01970	784
FKBP2	FTH1	P02794	779
FKBP2	AHNAK	Q09666	778
FKBP2	PYGM	P11217	774
FKBP2	SF1	Q15637	774
FKBP2	FOSL1	P15407	769
FKBP2	MARK2	Q7KZI7	769
FKBP2	MAP3K11	Q16584	768
FKBP2	COX8A	P10176	768
FKBP2	ROM1	Q03395	766
FKBP2	CHRM1	P11229	766
FKBP2	CAPN1	P07384	765
FKBP2	SCGB1A1	P11684	764
FKBP2	PPIF	P30405	731
FKBP2	PPIA	P05092	730

IntAct

40 interactions, top by confidence:

A	B	Type	Score
UBQLN1	FKBP2	psi-mi:“MI:0915”(physical association)	0.560
FKBP2	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
FKBP2	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
FKBP2	HTT	psi-mi:“MI:0915”(physical association)	0.560
FKBP2	ATXN1	psi-mi:“MI:0915”(physical association)	0.560
FKBP2	TTC13	psi-mi:“MI:0914”(association)	0.530
UBQLN4	FKBP2	psi-mi:“MI:0915”(physical association)	0.510
RPL19	FKBP2	psi-mi:“MI:0915”(physical association)	0.400
KATNAL1	FKBP2	psi-mi:“MI:0915”(physical association)	0.400
FKBP2	Pdia3	psi-mi:“MI:0915”(physical association)	0.400
S100A9	FKBP2	psi-mi:“MI:0915”(physical association)	0.370
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
FKBP2	HLA-DQA1	psi-mi:“MI:0914”(association)	0.350
LYZ	FKBP2	psi-mi:“MI:0914”(association)	0.350

BioGRID (88): UBQLN1 (Two-hybrid), ACAA2 (Co-fractionation), ALDOA (Co-fractionation), ALDOC (Co-fractionation), ATP6AP2 (Co-fractionation), CRYZ (Co-fractionation), DNAJC2 (Co-fractionation), ENO1 (Co-fractionation), ENO2 (Co-fractionation), ENO3 (Co-fractionation), FKBP1A (Co-fractionation), FKBP2 (Co-fractionation), FKBP2 (Co-fractionation), FKBP2 (Co-fractionation), FKBP2 (Co-fractionation)

ESM2 similar proteins: O04287, O42123, O42993, O94746, P0A0W2, P0A0W3, P0C1J3, P0CP94, P0CP95, P0CY37, P18203, P20080, P20081, P26883, P26885, P28725, P28870, P32472, P45878, P48375, P56989, P62942, P62943, P68106, P68107, P97534, Q2U316, Q2UPT7, Q32PA9, Q38931, Q43207, Q4HZB8, Q4W9R2, Q4WHX4, Q4WLV6, Q554J3, Q5ATN7, Q5VVH2, Q62658, Q6BX45

Diamond homologs: A5IGB8, G0SC91, O04287, O08437, O42123, O42993, O46638, O94746, O95302, P0A0W2, P0A0W3, P0A9L3, P0A9L4, P0C1B0, P0C1J3, P0C1J5, P0C1J6, P0C1J7, P0CP94, P0CP95, P0CP96, P0CP97, P18203, P20081, P26623, P26884, P26885, P27124, P28870, P30416, P31106, P38911, P44760, P45523, P45878, P48375, P51752, P53605, P54397, P56989

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	11
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

882 predictions. Top by Δscore:

Variant	Effect	Δscore
11:64241129:GGAG:G	donor_gain	1.0000
11:64241130:G:GT	donor_gain	1.0000
11:64241133:GT:G	donor_loss	1.0000
11:64241134:T:A	donor_loss	1.0000
11:64242417:A:AG	acceptor_gain	1.0000
11:64242418:G:GG	acceptor_gain	1.0000
11:64242418:GTACT:G	acceptor_gain	1.0000
11:64242557:CGGTG:C	donor_loss	1.0000
11:64242559:G:A	donor_loss	1.0000
11:64242559:G:GG	donor_gain	1.0000
11:64242560:T:G	donor_loss	1.0000
11:64243188:T:TA	acceptor_gain	1.0000
11:64243195:A:AG	acceptor_gain	1.0000
11:64243195:ACAG:A	acceptor_gain	1.0000
11:64243195:ACAGG:A	acceptor_gain	1.0000
11:64243197:A:AG	acceptor_gain	1.0000
11:64243197:A:C	acceptor_loss	1.0000
11:64243197:AG:A	acceptor_gain	1.0000
11:64243197:AGG:A	acceptor_gain	1.0000
11:64243197:AGGG:A	acceptor_gain	1.0000
11:64243198:G:GA	acceptor_gain	1.0000
11:64243198:GG:G	acceptor_gain	1.0000
11:64243198:GGG:G	acceptor_gain	1.0000
11:64243198:GGGG:G	acceptor_gain	1.0000
11:64243198:GGGGA:G	acceptor_gain	1.0000
11:64243309:GGG:G	donor_gain	1.0000
11:64243310:GG:G	donor_gain	1.0000
11:64243310:GGG:G	donor_gain	1.0000
11:64243311:GG:G	donor_gain	1.0000
11:64243311:GGT:G	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000786292 (11:64242055 G>C), RS1001341927 (11:64244465 A>C), RS1001714431 (11:64244345 T>C), RS1002273209 (11:64242940 C>T), RS1002281578 (11:64239338 T>G), RS1002312467 (11:64239189 G>A), RS1002324109 (11:64242675 C>T), RS1002662663 (11:64240545 C>T), RS1003274829 (11:64244455 C>G,T), RS1003325768 (11:64244186 C>T), RS1004738401 (11:64244635 G>A), RS1004829574 (11:64244446 G>C), RS1005237106 (11:64244496 G>A,C), RS1005624047 (11:64240416 A>T), RS1005657108 (11:64239753 C>T)

Disease associations

OMIM: gene MIM:186946 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004132_98	Crohn’s disease	5.000000e-06
GCST010136_47	Fruit consumption	9.000000e-10
GCST012465_38	Bipolar disorder	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105949 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.22	Ki	60.5	nM	CHEMBL4090599
5.98	Kd	1053	nM	CHEMBL3623630

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(1S,5S,6R)-10-(3,5-dichlorophenyl)sulfonyl-5-(methoxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one	1479801: Displacement of 5-(3-(4-(((5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-5-vinyl-3,10-diazabicyclo[4.3.1]decan-3-yl)methyl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3,10-dihydroanthracen-9-yl)benzoate from human FKBP13 after 30 mins by fluorescence polarization assay	ki	0.0605	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	affects binding, increases reaction, decreases expression, increases expression	3
Cyclosporine	increases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	2
Thapsigargin	increases expression	2
2,4,6-tribromophenol	increases expression	1
decabromobiphenyl ether	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	increases expression	1
ochratoxin A	increases acetylation, increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Vehicle Emissions	decreases expression, decreases reaction	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects response to substance	1
Diazinon	increases methylation	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
Tretinoin	increases expression	1
Tunicamycin	increases expression	1
Valproic Acid	increases methylation	1
Zinc	increases expression	1
Sodium Selenite	increases expression	1
Cadmium Chloride	increases expression, increases abundance	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4048816	Binding	Displacement of 5-(3-(4-(((5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-5-vinyl-3,10-diazabicyclo[4.3.1]decan-3-yl)methyl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3,10-dihydroanthracen-9-yl)benzoate fr	Chemogenomic Profiling of Human and Microbial FK506-Binding Proteins. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2X5	Abcam HEK293T FKBP2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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