FKBP9

Summary

FKBP9 (FKBP prolyl isomerase 9, HGNC:3725) is a protein-coding gene on chromosome 7p14.3, encoding Peptidyl-prolyl cis-trans isomerase FKBP9 (O95302). PPIases accelerate the folding of proteins during protein synthesis.

Predicted to enable calcium ion binding activity and peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in protein folding. Predicted to be active in endoplasmic reticulum.

Source: NCBI Gene 11328 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 101 total
• MANE Select transcript: NM_007270

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3725
Approved symbol	FKBP9
Name	FKBP prolyl isomerase 9
Location	7p14.3
Locus type	gene with protein product
Status	Approved
Aliases	FKBP60, FKBP63
Ensembl gene	ENSG00000122642
Ensembl biotype	protein_coding
OMIM	616257
Entrez	11328

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 11 protein_coding, 7 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000242209, ENST00000418354, ENST00000463443, ENST00000464334, ENST00000468510, ENST00000469202, ENST00000471066, ENST00000472007, ENST00000475220, ENST00000485309, ENST00000489038, ENST00000490776, ENST00000494374, ENST00000538336, ENST00000875466, ENST00000875467, ENST00000875468, ENST00000875469, ENST00000875470, ENST00000970337, ENST00000970338

RefSeq mRNA: 3 — MANE Select: NM_007270 NM_001284341, NM_001284343, NM_007270

CCDS: CCDS5439, CCDS64622, CCDS64623

Canonical transcript exons

ENST00000242209 — 10 exons

Exon	Start	End
ENSE00001274526	33005175	33006928
ENSE00001314638	32957440	32957794
ENSE00003474098	32975182	32975371
ENSE00003493593	32996163	32996349
ENSE00003532579	32980364	32980553
ENSE00003542786	32976354	32976499
ENSE00003551162	33002676	33002839
ENSE00003629397	32974617	32974762
ENSE00003640540	33000115	33000260
ENSE00003659200	32988507	32988652

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 99.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.8671 / max 364.4530, expressed in 1631 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78058	34.7687	1626
78059	5.4884	961
78060	0.2724	127
204408	0.1751	83
204407	0.1234	57
78061	0.0277	7
78062	0.0114	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.27	gold quality
colonic epithelium	UBERON:0000397	98.14	gold quality
calcaneal tendon	UBERON:0003701	98.08	gold quality
smooth muscle tissue	UBERON:0001135	97.91	gold quality
placenta	UBERON:0001987	97.81	gold quality
gall bladder	UBERON:0002110	97.31	gold quality
descending thoracic aorta	UBERON:0002345	96.97	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.83	gold quality
thoracic aorta	UBERON:0001515	96.59	gold quality
ascending aorta	UBERON:0001496	96.57	gold quality
right coronary artery	UBERON:0001625	96.50	gold quality
rectum	UBERON:0001052	96.42	gold quality
apex of heart	UBERON:0002098	96.30	gold quality
islet of Langerhans	UBERON:0000006	96.24	gold quality
myometrium	UBERON:0001296	96.21	gold quality
fallopian tube	UBERON:0003889	96.21	gold quality
adipose tissue	UBERON:0001013	96.17	gold quality
skin of leg	UBERON:0001511	96.16	gold quality
ventricular zone	UBERON:0003053	96.02	gold quality
right atrium auricular region	UBERON:0006631	96.00	gold quality
zone of skin	UBERON:0000014	95.99	gold quality
heart	UBERON:0000948	95.99	gold quality
heart left ventricle	UBERON:0002084	95.93	gold quality
mammary gland	UBERON:0001911	95.79	gold quality
thoracic mammary gland	UBERON:0005200	95.79	gold quality
nerve	UBERON:0001021	95.77	gold quality
tibial nerve	UBERON:0001323	95.77	gold quality
skin of abdomen	UBERON:0001416	95.67	gold quality
uterine cervix	UBERON:0000002	95.66	gold quality
urinary bladder	UBERON:0001255	95.64	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	13.43
E-MTAB-6678	yes	12.46
E-MTAB-5061	yes	11.28
E-MTAB-7052	no	308.88
E-MTAB-10137	no	5.32
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting FKBP9, 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-4789-5P	99.98	70.76	2721
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-3117-5P	99.04	67.93	618
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-382-3P	98.83	67.10	1074
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359

Literature-anchored findings (GeneRIF, showing 2)

• Increasing of FKBP9 can predict poor prognosis in patients with prostate cancer. (PMID:31780055)
• FKBP9 promotes the malignant behavior of glioblastoma cells and confers resistance to endoplasmic reticulum stress inducers. (PMID:32111229)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fkbp9	ENSDARG00000005023
mus_musculus	Fkbp9	ENSMUSG00000029781
rattus_norvegicus	Fkbp9	ENSRNOG00000005478
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), TTC9 (ENSG00000133985), FKBP11 (ENSG00000134285), FKBP10 (ENSG00000141756), TTC9C (ENSG00000162222), FKBP2 (ENSG00000173486), TTC9B (ENSG00000174521), FKBP1C (ENSG00000198225), FKBPL (ENSG00000204315)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase FKBP9 — O95302 (reviewed: O95302)

Alternative names: 63 kDa FK506-binding protein, FK506-binding protein 9, Rotamase

All UniProt accessions (2): C9J4P8, O95302

UniProt curated annotations — full annotation on UniProt →

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

Subcellular location. Endoplasmic reticulum.

Post-translational modifications. Phosphorylated.

Activity regulation. Inhibited by FK506.

Isoforms (3)

UniProt ID	Names	Canonical?
O95302-1	1	yes
O95302-2	2
O95302-3	3

RefSeq proteins (3): NP_001271270, NP_001271272, NP_009201* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001179	PPIase_FKBP_dom	Domain
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR046357	PPIase_dom_sf	Homologous_superfamily
IPR051989	FKBP-like_isomerase	Family

Pfam: PF00254

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (25 total): binding site 10, domain 6, glycosylation site 4, splice variant 2, signal peptide 1, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95302-F1	89.24	0.77

Functional residue map

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

Ligand- & substrate-binding residues (10): 503; 505; 507; 512; 546; 548; 550; 552; 557; 501

Glycosylation sites (4): 174, 286, 302, 397

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis

MSigDB gene sets: 142 (showing top): BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, KAAB_FAILED_HEART_ATRIUM_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_PROTEIN_MATURATION, GNF2_CDH11, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, GOBP_PROTEIN_FOLDING, YAMAZAKI_TCEB3_TARGETS_UP, MODULE_18, SENESE_HDAC3_TARGETS_DN, GOMF_CIS_TRANS_ISOMERASE_ACTIVITY, MATSUDA_NATURAL_KILLER_DIFFERENTIATION, WANG_TUMOR_INVASIVENESS_UP

GO Biological Process (1): protein folding (GO:0006457)

GO Molecular Function (4): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), calcium ion binding (GO:0005509), isomerase activity (GO:0016853), metal ion binding (GO:0046872)

GO Cellular Component (1): endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Chaperonin-mediated protein folding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
protein maturation	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
metal ion binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2492 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FKBP9	NR2C1	P13056	560
FKBP9	ZNF500	O60304	475
FKBP9	ZMYM4	Q5VZL5	453
FKBP9	PTGR3	Q8N4Q0	445
FKBP9	INO80E	Q8NBZ0	422
FKBP9	UBE2I	P50550	418
FKBP9	FBXL20	Q96IG2	410
FKBP9	TBCCD1	Q9NVR7	403
FKBP9	KCNH8	Q96L42	402
FKBP9	RCN3	Q96D15	400
FKBP9	RFTN2	Q52LD8	398
FKBP9	DTYMK	P23919	395
FKBP9	MDM4	O15151	392
FKBP9	GSTP1	P09211	389
FKBP9	GFOD2	Q3B7J2	387

IntAct

18 interactions, top by confidence:

A	B	Type	Score
FKBP9	CASC3	psi-mi:“MI:0914”(association)	0.530
LAIR2	LAMA5	psi-mi:“MI:0914”(association)	0.530
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500
CDC42	BBX	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
	ZNF316	psi-mi:“MI:0914”(association)	0.350
FKBP9	COL2A1	psi-mi:“MI:0914”(association)	0.350
ADAMTS12	FKBP9	psi-mi:“MI:0914”(association)	0.350
	VPS37C	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ADAMTS12	LRP6	psi-mi:“MI:0914”(association)	0.350
FKBP9	WASL	psi-mi:“MI:0914”(association)	0.350
MFSD3	NME4	psi-mi:“MI:0914”(association)	0.350
SLC10A7	NUP155	psi-mi:“MI:0914”(association)	0.350
SLC22A23	NRP1	psi-mi:“MI:0914”(association)	0.350
SPNS2	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (96): FKBP9 (Affinity Capture-MS), FKBP9 (Affinity Capture-MS), CHTF8 (Affinity Capture-MS), TCF20 (Affinity Capture-MS), RAVER1 (Affinity Capture-MS), CBY1 (Affinity Capture-MS), TCF3 (Affinity Capture-MS), COL4A6 (Affinity Capture-MS), COL2A1 (Affinity Capture-MS), PTPRS (Affinity Capture-MS), FKBP9 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), DAG1 (Affinity Capture-MS), FN1 (Affinity Capture-MS), PRCC (Affinity Capture-MS)

ESM2 similar proteins: A6QPY0, D2XV59, O00178, O08582, O54734, O60568, O77783, O95302, P00533, P18614, P39656, P55245, P56199, P70428, P83337, Q01279, Q05052, Q13822, Q29381, Q2KJ84, Q2KJC8, Q3V3R4, Q58DC5, Q5R6K5, Q5R809, Q5R8Q7, Q5U4X8, Q641Y0, Q66H94, Q6EV69, Q6GMK0, Q6GQK9, Q6IS24, Q6V9H4, Q6ZQ11, Q75LS8, Q7TT15, Q7Z4H8, Q86X52, Q8BFR2

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3744 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:32976452:G:C	R219P	1.000
7:33000213:G:C	R442P	1.000
7:32975325:T:G	Y171D	0.999
7:32975337:G:T	G175W	0.999
7:32975338:G:A	G175E	0.999
7:32975367:T:C	S185P	0.999
7:32976401:T:C	L202P	0.999
7:32976421:G:A	G209R	0.999
7:32976421:G:C	G209R	0.999
7:32976421:G:T	G209W	0.999
7:32976425:T:C	L210P	0.999
7:32988605:G:C	R331P	0.999
7:32957746:G:C	R58P	0.998
7:32957748:T:G	Y59D	0.998
7:32957793:A:C	S74R	0.998
7:32974617:C:A	S74R	0.998
7:32974617:C:G	S74R	0.998
7:32974688:T:C	L98P	0.998
7:32975232:G:C	D140H	0.998
7:32975361:T:C	F183L	0.998
7:32975363:T:A	F183L	0.998
7:32975363:T:G	F183L	0.998
7:32980391:T:C	L244P	0.998
7:33000186:T:C	L433P	0.998
7:32974699:T:A	C102S	0.997
7:32974700:G:C	C102S	0.997
7:32974715:G:C	R107P	0.997
7:32975215:T:C	F134S	0.997
7:32975233:A:T	D140V	0.997
7:32975314:A:T	D167V	0.997

dbSNP variants (sampled 300 via entrez): RS1000008034 (7:32987447 A>C), RS1000131311 (7:32979340 G>T), RS1000239079 (7:33004395 A>G), RS1000305806 (7:32958177 C>T), RS1000397367 (7:32986366 C>T), RS1000554604 (7:32959630 T>C), RS1000609591 (7:32960223 T>G), RS1000661007 (7:33003544 A>T), RS1000679554 (7:32997706 T>C), RS1000716305 (7:32997442 C>G,T), RS1000963391 (7:32972804 C>A,T), RS1001134408 (7:32998783 G>A,T), RS1001165459 (7:32998493 G>C), RS1001187794 (7:32991205 C>T), RS1001286853 (7:32992194 C>T)

Disease associations

OMIM: gene MIM:616257 | 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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment	2
bisphenol A	affects cotreatment, increases expression, decreases expression	2
bisphenol S	increases expression, affects cotreatment	2
Cadmium	increases abundance, increases palmitoylation, increases expression, decreases reaction	2
aristolochic acid I	decreases expression	1
sodium arsenate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
perfluorooctanoic acid	decreases expression	1
bleomycetin	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
entinostat	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
bisphenol AF	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1

Clinical trials (associated diseases)

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