FKBP11

Summary

FKBP11 (FKBP prolyl isomerase 11, HGNC:18624) is a protein-coding gene on chromosome 12q13.12, encoding Peptidyl-prolyl cis-trans isomerase FKBP11 (Q9NYL4). PPIases accelerate the folding of proteins during protein synthesis.

FKBP11 belongs to the FKBP family of peptidyl-prolyl cis/trans isomerases, which catalyze the folding of proline-containing polypeptides. The peptidyl-prolyl isomerase activity of FKBP proteins is inhibited by the immunosuppressant compounds FK506 and rapamycin (Rulten et al., 2006 [PubMed 16596453]).

Source: NCBI Gene 51303 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_016594

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18624
Approved symbol	FKBP11
Name	FKBP prolyl isomerase 11
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Aliases	FKBP19
Ensembl gene	ENSG00000134285
Ensembl biotype	protein_coding
OMIM	610571
Entrez	51303

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 6 retained_intron, 5 protein_coding, 3 nonsense_mediated_decay

ENST00000256680, ENST00000444214, ENST00000453172, ENST00000546671, ENST00000546847, ENST00000547789, ENST00000549084, ENST00000550765, ENST00000551094, ENST00000551694, ENST00000551807, ENST00000552878, ENST00000553027, ENST00000890173

RefSeq mRNA: 3 — MANE Select: NM_016594 NM_001143781, NM_001143782, NM_016594

CCDS: CCDS44870, CCDS44871, CCDS8773

Canonical transcript exons

ENST00000550765 — 6 exons

Exon	Start	End
ENSE00002387756	48925300	48925492
ENSE00003483899	48923782	48923852
ENSE00003586926	48925046	48925111
ENSE00003606638	48924561	48924648
ENSE00003670507	48924223	48924256
ENSE00003847386	48921963	48922201

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.5241 / max 416.7031, expressed in 1421 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130747	12.0441	1386
130748	1.8629	916
130746	0.6172	332

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.26	gold quality
parotid gland	UBERON:0001831	97.72	gold quality
pancreas	UBERON:0001264	97.22	gold quality
stromal cell of endometrium	CL:0002255	96.21	gold quality
adenohypophysis	UBERON:0002196	96.19	gold quality
pituitary gland	UBERON:0000007	95.94	gold quality
islet of Langerhans	UBERON:0000006	95.75	gold quality
saliva-secreting gland	UBERON:0001044	95.66	gold quality
granulocyte	CL:0000094	95.40	gold quality
rectum	UBERON:0001052	95.36	gold quality
spleen	UBERON:0002106	95.27	gold quality
minor salivary gland	UBERON:0001830	95.09	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.87	gold quality
vermiform appendix	UBERON:0001154	94.50	gold quality
colonic epithelium	UBERON:0000397	94.49	gold quality
right lobe of liver	UBERON:0001114	94.06	gold quality
mucosa of transverse colon	UBERON:0004991	93.91	gold quality
body of stomach	UBERON:0001161	93.33	gold quality
tonsil	UBERON:0002372	93.20	gold quality
endocervix	UBERON:0000458	93.09	gold quality
lymph node	UBERON:0000029	93.07	gold quality
bone marrow cell	CL:0002092	93.04	gold quality
trachea	UBERON:0003126	92.66	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.44	gold quality
pylorus	UBERON:0001166	92.43	gold quality
upper lobe of left lung	UBERON:0008952	92.32	gold quality
omental fat pad	UBERON:0010414	92.32	gold quality
peritoneum	UBERON:0002358	92.27	gold quality
stomach	UBERON:0000945	92.16	gold quality
decidua	UBERON:0002450	92.03	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 27.

Experiment	Marker?	Max mean expression
E-HCAD-32	yes	2054.37
E-MTAB-6653	yes	1635.06
E-MTAB-10432	yes	1543.46
E-MTAB-8530	yes	1307.71
E-CURD-126	yes	1184.19
E-MTAB-8410	yes	1156.10
E-MTAB-9467	yes	1148.22
E-HCAD-9	yes	1130.51
E-CURD-46	yes	1104.11
E-HCAD-4	yes	1082.50
E-HCAD-1	yes	997.23
E-MTAB-6308	yes	988.80
E-HCAD-15	yes	982.89
E-MTAB-10662	yes	941.56
E-MTAB-8322	yes	913.32

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 6)

• results suggest a progressively elevated expression of FKBP11 during the development of hepatocellular carcinoma (PMID:23749938)
• 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)
• FKBP11 promotes cell proliferation and tumorigenesis via p53-related pathways in oral squamous cell carcinoma. (PMID:33945996)
• FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis. (PMID:35456020)
• FKBP11 improves the malignant property of osteosarcoma cells and acts as a prognostic factor of osteosarcoma. (PMID:37014329)
• FKBP11 upregulation promotes proliferation and migration in hepatocellular carcinoma. (PMID:37248890)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fkbp11	ENSDARG00000037000
mus_musculus	Fkbp11	ENSMUSG00000003355
caenorhabditis_elegans		WBGENE00001429
caenorhabditis_elegans	fkb-5	WBGENE00001430

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), FKBP10 (ENSG00000141756), TTC9C (ENSG00000162222), FKBP2 (ENSG00000173486), TTC9B (ENSG00000174521), FKBP1C (ENSG00000198225), FKBPL (ENSG00000204315)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase FKBP11 — Q9NYL4 (reviewed: Q9NYL4)

Alternative names: 19 kDa FK506-binding protein, FK506-binding protein 11, Rotamase

All UniProt accessions (6): E9PAR0, Q9NYL4, F8VU90, F8VXK0, H0YHM7, J3KN11

UniProt curated annotations — full annotation on UniProt →

Function. PPIases accelerate the folding of proteins during protein synthesis.

Subunit / interactions. Interacts with IFITM5.

Subcellular location. Membrane.

Similarity. Belongs to the FKBP-type PPIase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NYL4-1	1	yes
Q9NYL4-2	2

RefSeq proteins (3): NP_001137253, NP_001137254, NP_057678* (*=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 (5 total): signal peptide 1, chain 1, transmembrane region 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9N9J	ELECTRON MICROSCOPY	3.2
9YGY	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYL4-F1	87.52	0.60

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 187 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, MCLACHLAN_DENTAL_CARIES_UP, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, USF_C, PATIL_LIVER_CANCER, SHAFFER_IRF4_TARGETS_IN_PLASMA_CELL_VS_MATURE_B_LYMPHOCYTE, ONKEN_UVEAL_MELANOMA_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, MYCMAX_01, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_DENDRITIC_CELL, FARMER_BREAST_CANCER_CLUSTER_1, LINDVALL_IMMORTALIZED_BY_TERT_UP

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

GO Molecular Function (2): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), isomerase activity (GO:0016853)

GO Cellular Component (2): endoplasmic reticulum (GO:0005783), 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
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1863 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FKBP11	CD9	P21926	895
FKBP11	CD81	P18582	718
FKBP11	PAX4	O43316	714
FKBP11	NKX2-5	P52952	639
FKBP11	PTGFRN	Q9P2B2	616
FKBP11	IFITM5	A6NNB3	510
FKBP11	DERL3	Q96Q80	507
FKBP11	PDIA4	P13667	487
FKBP11	CD79A	P11912	461
FKBP11	XBP1	P17861	432
FKBP11	PPIB	P23284	399
FKBP11	SERPINE2	P07093	398
FKBP11	HSP90B1	P14625	369
FKBP11	SEC11C	Q9BY50	366
FKBP11	COMMD6	Q7Z4G1	362
FKBP11	DNAJC3	Q13217	362

IntAct

10 interactions, top by confidence:

A	B	Type	Score
FKBP11	ANKRD13D	psi-mi:“MI:0914”(association)	0.530
FKBP11	RELA	psi-mi:“MI:0915”(physical association)	0.370
NCAPD3	NDUFS8	psi-mi:“MI:0914”(association)	0.350
SLC39A14	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A7	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC6A11	ILVBL	psi-mi:“MI:0914”(association)	0.350
FOS	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): FKBP11 (Affinity Capture-MS), GOPC (Affinity Capture-MS), ANKRD13D (Affinity Capture-MS), AHNAK2 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), FKBP11 (Affinity Capture-MS), FKBP11 (Affinity Capture-MS), FKBP11 (Proximity Label-MS), FKBP11 (Proximity Label-MS), FKBP11 (Proximity Label-MS), AHNAK2 (Affinity Capture-MS), GOPC (Affinity Capture-MS), ANKRD13D (Affinity Capture-MS), HDGFRP2 (Affinity Capture-MS), CBX8 (Affinity Capture-MS)

ESM2 similar proteins: H0ZAB5, O35548, O46638, O54998, O61394, O73798, O77636, P0C1J4, P0C1J5, P0CP96, P0CP97, P26884, P29120, P32472, P34714, P45878, P51512, P59024, P63239, P63240, P70419, P78536, Q00688, Q14435, Q19267, Q32PA9, Q38935, Q38936, Q41649, Q5BKL9, Q5R941, Q5RET2, Q5RF88, Q5ZKE5, Q62446, Q66JA6, Q6CGG3, Q6CUZ8, Q6FSC1, Q6WV20

Diamond homologs: A6QQ71, D3ZQF4, F6PHZ6, O42123, O42993, O46638, O54998, O75344, O94746, O95302, P0A0W2, P0A0W3, P0C1J3, P0C1J4, P0C1J5, P0C1J6, P0CP94, P0CP95, P0CP96, P0CP97, P18203, P20080, P20081, P26883, P26884, P26885, P27124, P28870, P30416, P30417, P32472, P44760, P45523, P45878, P48375, P54397, P56989, P57599, P62942, P62943

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1580 predictions. Top by Δscore:

Variant	Effect	Δscore
12:48922015:T:TA	donor_gain	0.9900
12:48922198:TCCG:T	acceptor_gain	0.9900
12:48922199:CCG:C	acceptor_gain	0.9900
12:48922199:CCGC:C	acceptor_gain	0.9900
12:48922200:CGC:C	acceptor_gain	0.9900
12:48922202:C:CC	acceptor_gain	0.9900
12:48924773:CCG:C	donor_gain	0.9900
12:48922200:CG:C	acceptor_gain	0.9800
12:48922201:GC:G	acceptor_loss	0.9700
12:48922202:C:CA	acceptor_loss	0.9700
12:48922203:T:A	acceptor_loss	0.9700
12:48924644:CTTCC:C	acceptor_gain	0.9700
12:48922126:CCCT:C	donor_gain	0.9600
12:48922130:TC:T	donor_gain	0.9600
12:48923955:C:T	acceptor_gain	0.9600
12:48924221:AC:A	donor_gain	0.9600
12:48924222:CC:C	donor_gain	0.9600
12:48925247:C:CT	donor_gain	0.9600
12:48924221:ACC:A	donor_gain	0.9500
12:48924222:CCC:C	donor_gain	0.9500
12:48924222:CCCCA:C	donor_gain	0.9500
12:48924258:T:C	acceptor_gain	0.9500
12:48924856:C:CC	acceptor_gain	0.9500
12:48925294:CCTCA:C	donor_loss	0.9500
12:48925295:CTCA:C	donor_loss	0.9500
12:48925296:TCAC:T	donor_loss	0.9500
12:48925297:C:CC	donor_loss	0.9500
12:48924869:A:T	acceptor_gain	0.9400
12:48925298:A:AC	donor_gain	0.9400
12:48925299:C:CC	donor_gain	0.9400

AlphaMissense

1268 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:48923844:C:G	R109P	0.999
12:48924241:A:G	L100P	0.998
12:48924241:A:T	L100H	0.996
12:48924253:A:G	L96P	0.996
12:48924647:C:T	G66E	0.996
12:48925056:A:T	I62K	0.996
12:48922072:C:T	G173E	0.995
12:48922093:G:C	P166R	0.995
12:48922196:C:G	A132P	0.995
12:48923787:A:T	V128D	0.995
12:48923811:C:A	G120V	0.995
12:48924256:C:T	G95D	0.995
12:48924614:G:A	S77F	0.995
12:48922171:A:G	L140P	0.994
12:48923817:G:T	A118D	0.994
12:48923832:A:T	I113N	0.994
12:48925062:A:T	L60H	0.994
12:48923832:A:G	I113T	0.993
12:48924243:A:C	S99R	0.993
12:48924243:A:T	S99R	0.993
12:48924245:T:G	S99R	0.993
12:48924561:C:G	G95R	0.993
12:48922073:C:G	G173R	0.992
12:48922073:C:T	G173R	0.992
12:48922082:C:G	G170R	0.992
12:48923803:C:G	G123R	0.992
12:48923803:C:T	G123R	0.992
12:48924584:A:T	L87H	0.992
12:48924615:A:G	S77P	0.992
12:48924648:C:G	G66R	0.992

dbSNP variants (sampled 300 via entrez): RS1000168715 (12:48926154 T>A,C), RS1000288735 (12:48925458 C>A,G), RS1000314829 (12:48940062 A>G), RS1000418782 (12:48931799 T>C), RS1000524980 (12:48933598 G>A), RS1001035171 (12:48927270 T>C), RS1001047939 (12:48938245 T>C), RS1001124911 (12:48932801 GCGGACAAGC>G), RS1001417079 (12:48933572 C>A,T), RS1001479031 (12:48938742 C>G,T), RS1001652270 (12:48939917 G>A,C,T), RS1001772416 (12:48932083 G>A), RS1001816587 (12:48933240 A>G), RS1002139700 (12:48922328 G>C), RS1002257176 (12:48927982 T>C)

Disease associations

OMIM: gene MIM:610571 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	4
(+)-JQ1 compound	decreases expression	3
trichostatin A	affects cotreatment, increases expression	2
cobaltous chloride	decreases expression	2
entinostat	increases expression, affects cotreatment	2
Nickel	increases expression	2
Tunicamycin	increases expression	2
Thapsigargin	increases expression	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
butyraldehyde	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
pentanal	increases expression	1
bicalutamide	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	increases reaction, affects binding	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	affects expression, affects methylation	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol AF	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
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1

Clinical trials (associated diseases)

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