FKBP10

Summary

FKBP10 (FKBP prolyl isomerase 10, HGNC:18169) is a protein-coding gene on chromosome 17q21.2, encoding Peptidyl-prolyl cis-trans isomerase FKBP10 (Q96AY3). PPIases accelerate the folding of proteins during protein synthesis.

The protein encoded by this gene belongs to the FKBP-type peptidyl-prolyl cis/trans isomerase (PPIase) family. This protein localizes to the endoplasmic reticulum and acts as a molecular chaperone. Alternatively spliced variants encoding different isoforms have been reported, but their biological validity has not been determined.

Source: NCBI Gene 60681 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Bruck syndrome 1 (Definitive, GenCC) — +7 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 752 total — 52 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 233
• MANE Select transcript: NM_021939

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18169
Approved symbol	FKBP10
Name	FKBP prolyl isomerase 10
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	hFKBP65, FKBP65, FLJ22041, FKBP6, FLJ20683, FLJ23833
Ensembl gene	ENSG00000141756
Ensembl biotype	protein_coding
OMIM	607063
Entrez	60681

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 31 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000321562, ENST00000429461, ENST00000455106, ENST00000464180, ENST00000487489, ENST00000489591, ENST00000490938, ENST00000585664, ENST00000585922, ENST00000706683, ENST00000864392, ENST00000864393, ENST00000864394, ENST00000864395, ENST00000864396, ENST00000864397, ENST00000864398, ENST00000864399, ENST00000864400, ENST00000864401, ENST00000914591, ENST00000914592, ENST00000914593, ENST00000914594, ENST00000914595, ENST00000914596, ENST00000914597, ENST00000914598, ENST00000914599, ENST00000914600, ENST00000914601, ENST00000914602, ENST00000914603, ENST00000914604, ENST00000914605

RefSeq mRNA: 1 — MANE Select: NM_021939 NM_021939

CCDS: CCDS11409

Canonical transcript exons

ENST00000321562 — 10 exons

Exon	Start	End
ENSE00001607859	41822223	41823213
ENSE00001866839	41813004	41813279
ENSE00002431516	41817058	41817203
ENSE00002431846	41819530	41819675
ENSE00003520270	41820947	41821089
ENSE00003548940	41818382	41818527
ENSE00003596718	41820269	41820461
ENSE00003628657	41821654	41821817
ENSE00003662726	41818089	41818278
ENSE00003689120	41819210	41819399

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 99.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 146.4793 / max 2955.2226, expressed in 1460 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160873	137.2270	1352
160872	7.0748	1349
160879	1.3568	654
160878	0.8207	483

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.51	gold quality
ascending aorta	UBERON:0001496	98.21	gold quality
thoracic aorta	UBERON:0001515	98.19	gold quality
descending thoracic aorta	UBERON:0002345	98.15	gold quality
adenohypophysis	UBERON:0002196	98.06	gold quality
right coronary artery	UBERON:0001625	97.88	gold quality
right ovary	UBERON:0002118	97.51	gold quality
endocervix	UBERON:0000458	97.45	gold quality
body of uterus	UBERON:0009853	97.43	gold quality
left ovary	UBERON:0002119	97.19	gold quality
left coronary artery	UBERON:0001626	97.07	gold quality
left uterine tube	UBERON:0001303	96.83	gold quality
aorta	UBERON:0000947	96.29	gold quality
gall bladder	UBERON:0002110	96.12	gold quality
coronary artery	UBERON:0001621	95.96	gold quality
pituitary gland	UBERON:0000007	95.83	gold quality
right adrenal gland	UBERON:0001233	95.77	gold quality
smooth muscle tissue	UBERON:0001135	95.62	gold quality
left adrenal gland cortex	UBERON:0035825	95.53	gold quality
right adrenal gland cortex	UBERON:0035827	95.51	gold quality
right lobe of thyroid gland	UBERON:0001119	95.49	gold quality
mucosa of stomach	UBERON:0001199	95.47	gold quality
left adrenal gland	UBERON:0001234	95.40	gold quality
popliteal artery	UBERON:0002250	95.21	gold quality
tibial artery	UBERON:0007610	95.21	gold quality
ventricular zone	UBERON:0003053	95.20	gold quality
tibial nerve	UBERON:0001323	94.78	gold quality
left lobe of thyroid gland	UBERON:0001120	94.63	gold quality
right atrium auricular region	UBERON:0006631	94.48	gold quality
ectocervix	UBERON:0012249	94.37	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	416.68
E-MTAB-10287	yes	108.53
E-HCAD-1	yes	76.26
E-MTAB-8410	yes	37.07
E-CURD-112	yes	18.52
E-ANND-3	yes	11.79
E-GEOD-83139	yes	7.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting FKBP10, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-7977	98.65	66.18	2590

Literature-anchored findings (GeneRIF, showing 37)

• Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. (PMID:20362275)
• FKBP10 mutations are a cause of recessive osteogenesis imperfecta and Bruck syndrome. (PMID:20839288)
• The differential expression of FKBP65 indicates a role in ovarian physiology as well as in ovarian tumor development (PMID:21399973)
• Mutations in FKBP10 cause both Bruck syndrome and isolated osteogenesis imperfecta in humans. (PMID:21567934)
• Homozygosity mapping identified FKBP10 as a candidate gene, and sequencing revealed a base pair exchange that causes a C-terminal premature stop codon in this gene. (PMID:22107750)
• identified a Palestinian pedigree with moderate and lethal forms of recessive OI caused by mutations in FKBP10 or PPIB, which encode endoplasmic reticulum resident chaperone/isomerases FKBP65 and CyPB, respectively (PMID:22718341)
• FKBP10 acts during procollagen maturation to contribute to molecular stability and post-translational modification of type I procollagen, without which bone mass and quality are abnormal and fractures and contractures result (PMID:22949511)
• underexpression of FKBP65 protein is characteristic of high-grade serous carcinomas and this expression profile may be linked to molecular pathways associated with an unfavourable outcome in cancer patients. (PMID:23354471)
• FKBP10 depletion enhances glucocerebrosidase proteostasis in Gaucher disease fibroblasts (PMID:23434032)
• Results imply that FKBP10 mutations affect collagen indirectly, by ablating FKBP65 support for collagen telopeptide hydroxylation by lysyl hydroxylase 2, thus decreasing collagen cross-links in tendon and bone matrix. (PMID:23712425)
• Elastin binding protein and FKBP65 modulate the kinetics of self-assembly of tropoelastin in an in vitro system. (PMID:24106871)
• CTSD, FKBP10, and SLC2A1 are novel genes that participate in the acquisition and maintenance of the adriamycin-resistant phenotype in leukemia cells. (PMID:24467213)
• Mutations in the HSP47 and FKBP65 produce a moderately severe form of Osteogenesis imperfect. (PMID:25510505)
• Mutations in FKBP10, localised to chromosome 17q21, have been identified in a patient of Bruck syndrome. Additional cases are also discussed. (PMID:25931047)
• findings further extend the body of evidence that supports the importance of FKBP10 gene in the development of skeletal system (PMID:26538303)
• FKBP65 is linked to pyridinoline cross-linking by specifically mediating the dimerization of LH2. (PMID:27298363)
• FKBP10 protein is overexpressed in renal cell carcinoma (PMID:27602571)
• A pathogenic change was found in the FKBP10 gene in patients with osteogenesis imperfecta. (PMID:27706701)
• novel pathogenic mutations of FKBP10 can lead to the extremely rare type XI Osteogenesis imperfecta without contractures, which expands the genotypic spectrum of Osteogenesis imperfecta. (PMID:27762305)
• an endoplasmic reticulum complex of resident chaperones that includes HSP47, FKBP65, and BiP regulating the activity of LH2. (PMID:28177155)
• 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)
• Data found novel mutations of the SERPINF1 and FKBP10 genes in Chinese families with autosomal recessive osteogenesis imperfecta (PMID:29512769)
• FKBP10 interacts with collagen VI and deficiency of FKBP10 reduces lung fibroblast migration by down-regulation of collage VI synthesis. (PMID:29673351)
• Study identified a private pathogenic splice site mutation in FKBP10 gene with nearly full decrease in the level of FKBP10 expression in the proband and around 75% decrease in its level in the carriers of the mutation suggesting its involvement in Osteogenesis imperfect. (PMID:29801479)
• High FKBP10 expression is associated with gastric cancer. (PMID:31233188)
• FKBP10 functioned as a cancer-promoting factor mediates cell proliferation, invasion, and migration via regulating PI3K signaling pathway in stomach adenocarcinoma. (PMID:31868996)
• FKBP10 Regulates Protein Translation to Sustain Lung Cancer Growth. (PMID:32187554)
• New insights on the clinical variability of FKBP10 mutations. (PMID:32531462)
• FKBP10 promotes proliferation of glioma cells via activating AKT-CREB-PCNA axis. (PMID:33557829)
• Long-Term Follow-Up Outcomes of 19 Patients with Osteogenesis Imperfecta Type XI and Bruck Syndrome Type I Caused by FKBP10 Variants. (PMID:34173012)
• FK506 binding protein 10: a key actor of collagen crosslinking in clear cell renal cell carcinoma. (PMID:34388114)
• circREEP3 Drives Colorectal Cancer Progression via Activation of FKBP10 Transcription and Restriction of Antitumor Immunity. (PMID:35233964)
• Bruck syndrome in 13 new patients: Identification of five novel FKBP10 and PLOD2 variants and further expansion of the phenotypic spectrum. (PMID:35278031)
• High VSX1 expression promotes the aggressiveness of clear cell renal cell carcinoma by transcriptionally regulating FKBP10. (PMID:36463181)
• Clinical features and molecular characterization of Chinese patients with FKBP10 variants. (PMID:36655627)
• Mutation In Fkbp10 Gene Cause Bruck Syndrome 1 (Brks1) In A Pakistani Family Of Pashtun Origin. (PMID:37422836)
• Presentation of Rare Phenotypes Associated with the FKBP10 Gene. (PMID:38927610)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	fkbp10b	ENSDARG00000045129
danio_rerio	fkbp10a	ENSDARG00000099183
mus_musculus	Fkbp10	ENSMUSG00000001555
rattus_norvegicus	Fkbp10	ENSRNOG00000015941
drosophila_melanogaster	Fkbp39	FBGN0013269
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), FKBP11 (ENSG00000134285), TTC9C (ENSG00000162222), FKBP2 (ENSG00000173486), TTC9B (ENSG00000174521), FKBP1C (ENSG00000198225), FKBPL (ENSG00000204315)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase FKBP10 — Q96AY3 (reviewed: Q96AY3)

Alternative names: 65 kDa FK506-binding protein, FK506-binding protein 10, Immunophilin FKBP65, Rotamase

All UniProt accessions (7): A0A9L9PY88, C9JPC3, Q96AY3, H0Y827, K7ELI6, K7EM43, K7ESG6

UniProt curated annotations — full annotation on UniProt →

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

Subcellular location. Endoplasmic reticulum lumen.

Post-translational modifications. Glycosylated and phosphorylated.

Disease relevance. Osteogenesis imperfecta 11 (OI11) [MIM:610968] A form of osteogenesis imperfecta, a disorder of bone formation characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI11 is an autosomal recessive form. The disease is caused by variants affecting the gene represented in this entry. Bruck syndrome 1 (BRKS1) [MIM:259450] A disease characterized by generalized osteopenia, congenital joint contractures, fragile bones with onset of fractures in infancy or early childhood, short stature, severe limb deformity, progressive scoliosis, and pterygia. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by both FK506 and rapamycin, but not by cyclosporin A.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96AY3-1	1	yes
Q96AY3-2	2

RefSeq proteins (1): NP_068758* (*=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, PF13202

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (39 total): binding site 10, glycosylation site 7, domain 6, sequence variant 5, splice variant 4, sequence conflict 2, signal peptide 1, chain 1, compositionally biased region 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AY3-F1	89.19	0.78

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): 510; 512; 514; 516; 521; 555; 557; 559; 561; 566

Glycosylation sites (7): 70, 182, 294, 310, 352, 393, 407

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 727 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, REACTOME_MEIOTIC_SYNAPSIS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_POSITIVE_REGULATION_OF_VIRAL_GENOME_REPLICATION, GOBP_ARTERY_DEVELOPMENT, GOBP_EXTRACELLULAR_MATRIX_ASSEMBLY, GOBP_MALE_GAMETE_GENERATION, GOBP_AORTA_DEVELOPMENT, GOBP_WOUND_HEALING, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_DNA_METHYLATION_DEPENDENT_CONSTITUTIVE_HETEROCHROMATIN_FORMATION, GOBP_PROTEIN_MATURATION

GO Biological Process (6): in utero embryonic development (GO:0001701), protein folding (GO:0006457), collagen fibril organization (GO:0030199), aorta morphogenesis (GO:0035909), wound healing (GO:0042060), extracellular matrix assembly (GO:0085029)

GO Molecular Function (6): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), calcium ion binding (GO:0005509), FK506 binding (GO:0005528), protein binding (GO:0005515), isomerase activity (GO:0016853), metal ion binding (GO:0046872)

GO Cellular Component (4): mitochondrial intermembrane space (GO:0005758), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
extracellular matrix organization	2
chordate embryonic development	1
cellular process	1
protein maturation	1
aorta development	1
artery morphogenesis	1
response to wounding	1
tissue regeneration	1
cellular component assembly	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
metal ion binding	1
macrolide binding	1
binding	1
catalytic activity	1
cation binding	1
mitochondrial envelope	1
organelle envelope lumen	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1
intracellular organelle lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3284 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FKBP10	ELN	P15502	924
FKBP10	PLOD2	O00469	915
FKBP10	SERPINH1	P29043	915
FKBP10	CRTAP	O75718	862
FKBP10	GTF2IRD1	Q9UHL9	834
FKBP10	PPIB	P23284	833
FKBP10	TMEM38B	Q9NVV0	828
FKBP10	P3H1	Q32P28	825
FKBP10	COL1A2	P02464	823
FKBP10	FZD9	O00144	788
FKBP10	TBL2	Q9Y4P3	758
FKBP10	TRIM50	Q86XT4	755
FKBP10	IFITM5	A6NNB3	735
FKBP10	GTF2I	P78347	725
FKBP10	CLIP2	Q9UDT6	718
FKBP10	SERPINF1	P36955	718

IntAct

46 interactions, top by confidence:

A	B	Type	Score
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
COL1A1	CRTAP	psi-mi:“MI:0915”(physical association)	0.580
SPRED1	FKBP10	psi-mi:“MI:0915”(physical association)	0.560
	PLOD2	psi-mi:“MI:0914”(association)	0.530
TMCC2	CORO1A	psi-mi:“MI:0914”(association)	0.530
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500
	TK2	psi-mi:“MI:0915”(physical association)	0.400
ORF27	GNPAT	psi-mi:“MI:0914”(association)	0.350
LAMP1	HAX1	psi-mi:“MI:0914”(association)	0.350
NUDCD1	TUBAL3	psi-mi:“MI:0914”(association)	0.350
TMCC2	MARK3	psi-mi:“MI:0914”(association)	0.350
FMC1	DNM1L	psi-mi:“MI:0914”(association)	0.350
CHCHD2	POLRMT	psi-mi:“MI:0914”(association)	0.350
CHCHD2	ACSL4	psi-mi:“MI:0914”(association)	0.350
SLX1A	PSMD11	psi-mi:“MI:0914”(association)	0.350
H2AX	ANXA6	psi-mi:“MI:0914”(association)	0.350
F	NSF	psi-mi:“MI:0914”(association)	0.350
	PLOD3	psi-mi:“MI:0914”(association)	0.350
	PLOD2	psi-mi:“MI:0914”(association)	0.350
rep	FKBP10	psi-mi:“MI:0914”(association)	0.350
	VPS37C	psi-mi:“MI:0914”(association)	0.350
INSR	HAX1	psi-mi:“MI:0914”(association)	0.350
SNRPF	SUPT5H	psi-mi:“MI:0914”(association)	0.350
FAM163B	TSPY2	psi-mi:“MI:0914”(association)	0.350
CCL18	PZP	psi-mi:“MI:0914”(association)	0.350
TMCC2	RPS4Y1	psi-mi:“MI:0914”(association)	0.350

BioGRID (143): FKBP10 (Proximity Label-MS), FKBP10 (Affinity Capture-MS), FKBP10 (Affinity Capture-MS), FKBP10 (Affinity Capture-MS), FKBP10 (Affinity Capture-MS), FKBP10 (Affinity Capture-RNA), FKBP10 (Affinity Capture-MS), FKBP10 (Affinity Capture-MS), FKBP10 (Co-fractionation), GRPEL1 (Co-fractionation), SDF4 (Co-fractionation), FKBP10 (Co-fractionation), FKBP10 (Co-fractionation), FKBP10 (Co-fractionation), FKBP10 (Co-fractionation)

ESM2 similar proteins: A4IHA1, A6YFB5, O54998, O60046, P0A0W2, P0A0W3, P0C1J4, P0C1J5, P0CP96, P0CP97, P0CY37, P20080, P26885, P27124, P28870, P32472, P45878, P59024, Q13451, Q2U316, Q2UPT7, Q2YDL5, Q32PA9, Q38935, Q38936, Q41649, Q4IN00, Q4W9R2, Q4WHX4, Q54N80, Q54SR7, Q5ATN7, Q5R941, Q5RET2, Q61576, Q6BP84, Q6CGG3, Q6CUZ8, Q6CX30, Q6FSC1

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

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

Classification	Count (floor)
Pathogenic	52
Likely pathogenic	28
Uncertain significance	252
Likely benign	311
Benign	33

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1298701	NM_021939.4(FKBP10):c.343C>T (p.Arg115Ter)	Pathogenic
1380263	NM_021939.4(FKBP10):c.612C>G (p.Tyr204Ter)	Pathogenic
1684032	NM_003602.5(FKBP6):c.589-2A>G	Pathogenic
1684033	NM_003602.5(FKBP6):c.508_529dup (p.Phe177fs)	Pathogenic
1687196	NM_021939.4(FKBP10):c.124G>T (p.Glu42Ter)	Pathogenic
2031705	NM_021939.4(FKBP10):c.9del (p.Ala4fs)	Pathogenic
208427	NM_021939.4(FKBP10):c.877_879del (p.Tyr293del)	Pathogenic
208646	NM_021939.4(FKBP10):c.1343_1344del (p.Val448fs)	Pathogenic
2128922	NM_021939.4(FKBP10):c.1243C>T (p.Gln415Ter)	Pathogenic
222952	NM_021939.4(FKBP10):c.976del (p.Met326fs)	Pathogenic
2426694	NC_000017.10:g.(?39969287)(39969551_?)del	Pathogenic
2574694	GRCh37/hg19 7q11.23(chr7:72664461-74162586)	Pathogenic
2696499	NM_021939.4(FKBP10):c.963_967dup (p.Ile323fs)	Pathogenic
2736585	NM_021939.4(FKBP10):c.310C>T (p.Arg104Ter)	Pathogenic
2736586	NM_021939.4(FKBP10):c.918-3C>G	Pathogenic
2736587	NM_021939.4(FKBP10):c.1399+1G>A	Pathogenic
2803887	NM_021939.4(FKBP10):c.1487_1497dup (p.Asp500fs)	Pathogenic
2806224	NM_021939.4(FKBP10):c.14dup (p.Ser8fs)	Pathogenic
2808092	NM_021939.4(FKBP10):c.1161del (p.Pro388fs)	Pathogenic
2823568	NM_021939.4(FKBP10):c.1247_1251dup (p.Thr418fs)	Pathogenic
2828109	NM_021939.4(FKBP10):c.910_914del (p.Asp304fs)	Pathogenic
2835222	NM_021939.4(FKBP10):c.1294del (p.Ala432fs)	Pathogenic
2846887	NM_021939.4(FKBP10):c.151_152insACCCCACA (p.Ile51fs)	Pathogenic
2858294	NM_021939.4(FKBP10):c.186_187insTG (p.Asp63fs)	Pathogenic
2858998	NM_021939.4(FKBP10):c.591_598dup (p.Thr200fs)	Pathogenic
288324	NM_021939.4(FKBP10):c.1399+2T>G	Pathogenic
3002030	NM_021939.4(FKBP10):c.1628del (p.Pro543fs)	Pathogenic
30631	NM_021939.4(FKBP10):c.1016_1023dup (p.Thr342fs)	Pathogenic
30632	NM_021939.4(FKBP10):c.122_156del (p.Leu41fs)	Pathogenic
30633	NM_021939.4(FKBP10):c.1276dup (p.Gln426fs)	Pathogenic

SpliceAI

3612 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41813275:TCAAG:T	donor_loss	1.0000
17:41813276:CAAG:C	donor_loss	1.0000
17:41813277:AAG:A	donor_loss	1.0000
17:41813278:AGG:A	donor_loss	1.0000
17:41813279:GGTAA:G	donor_loss	1.0000
17:41813280:G:GA	donor_loss	1.0000
17:41813281:T:G	donor_loss	1.0000
17:41817053:CCCA:C	acceptor_loss	1.0000
17:41817054:CCA:C	acceptor_loss	1.0000
17:41817055:CAG:C	acceptor_loss	1.0000
17:41817056:A:AG	acceptor_gain	1.0000
17:41817056:A:G	acceptor_loss	1.0000
17:41817057:G:GC	acceptor_gain	1.0000
17:41817057:GC:G	acceptor_gain	1.0000
17:41817057:GCT:G	acceptor_gain	1.0000
17:41817057:GCTA:G	acceptor_gain	1.0000
17:41817057:GCTAT:G	acceptor_gain	1.0000
17:41817189:G:GT	donor_gain	1.0000
17:41818087:A:AG	acceptor_gain	1.0000
17:41818087:AGC:A	acceptor_gain	1.0000
17:41818087:AGCG:A	acceptor_gain	1.0000
17:41818087:AGCGG:A	acceptor_gain	1.0000
17:41818088:G:GG	acceptor_gain	1.0000
17:41818088:GC:G	acceptor_gain	1.0000
17:41818088:GCG:G	acceptor_gain	1.0000
17:41818088:GCGG:G	acceptor_gain	1.0000
17:41818088:GCGGG:G	acceptor_gain	1.0000
17:41818104:C:A	acceptor_gain	1.0000
17:41818105:G:A	acceptor_gain	1.0000
17:41818128:T:TA	acceptor_gain	1.0000

AlphaMissense

3807 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41817156:G:C	R115P	0.999
17:41821045:G:C	R452P	0.999
17:41817140:T:A	C110S	0.998
17:41817141:G:C	C110S	0.998
17:41819237:T:C	L252P	0.998
17:41813231:G:C	R66P	0.997
17:41813233:T:G	Y67D	0.997
17:41813246:G:A	G71D	0.997
17:41813270:T:G	F79C	0.997
17:41817114:G:A	G101D	0.997
17:41817129:T:C	L106P	0.997
17:41817150:A:T	E113V	0.997
17:41818227:T:A	V177D	0.997
17:41818230:G:C	R178P	0.997
17:41819353:T:G	Y291D	0.997
17:41813270:T:C	F79S	0.996
17:41817125:G:C	G105R	0.996
17:41817126:G:A	G105D	0.996
17:41817162:T:C	L117P	0.996
17:41817180:T:C	L123P	0.996
17:41818232:T:G	Y179D	0.996
17:41818437:G:C	G213R	0.996
17:41818453:T:C	L218P	0.996
17:41819230:G:C	A250P	0.996
17:41820429:T:G	C408W	0.996
17:41821018:T:C	L443P	0.996
17:41821743:T:A	W497R	0.996
17:41821743:T:C	W497R	0.996
17:41813197:T:A	C55S	0.995
17:41813197:T:C	C55R	0.995

dbSNP variants (sampled 300 via entrez): RS1000123661 (17:41817715 G>A,C), RS1000252645 (17:41823378 G>C,T), RS1000517853 (17:41822073 C>A,T), RS1002288350 (17:41812783 G>A), RS1002471264 (17:41819056 C>A,T), RS1002958155 (17:41815527 G>A,T), RS1003137716 (17:41821508 T>C), RS1003302471 (17:41814685 G>C), RS1003380089 (17:41816017 C>G,T), RS1003475156 (17:41820173 G>A), RS1003853235 (17:41814249 G>A), RS1003919189 (17:41813917 C>T), RS1003962584 (17:41820122 A>C), RS1005526742 (17:41814590 G>T), RS1006417234 (17:41821179 G>A)

Disease associations

OMIM: gene MIM:607063 | disease phenotypes: MIM:610968, MIM:166200, MIM:259450, MIM:620103, MIM:609757, MIM:613849, MIM:166220, MIM:259420

GenCC curated gene-disease

Disease	Classification	Inheritance
Bruck syndrome 1	Definitive	Autosomal recessive
spermatogenic failure 77	Strong	Autosomal recessive
osteogenesis imperfecta type 11	Strong	Autosomal recessive
osteogenesis imperfecta	Strong	Autosomal recessive
arthrogryposis-like syndrome	Supportive	Autosomal recessive
osteogenesis imperfecta type 3	Supportive	Autosomal dominant
osteogenesis imperfecta type 4	Supportive	Autosomal dominant
Bruck syndrome	Supportive	Autosomal recessive

Mondo (11): osteogenesis imperfecta type 11 (MONDO:0012592), osteogenesis imperfecta (MONDO:0019019), Bruck syndrome 1 (MONDO:0009806), male infertility (MONDO:0005372), spermatogenic failure 77 (MONDO:0031083), 7q11.23 microduplication syndrome (MONDO:0012342), osteogenesis imperfecta type 12 (MONDO:0013460), osteogenesis imperfecta type 4 (MONDO:0008148), osteogenesis imperfecta type 3 (MONDO:0009804), Bruck syndrome (MONDO:0017195), arthrogryposis-like syndrome (MONDO:0015241)

Orphanet (6): Osteogenesis imperfecta (Orphanet:666), Kuskokwim syndrome (Orphanet:1149), Bruck syndrome (Orphanet:2771), 7q11.23 microduplication syndrome (Orphanet:96121), Osteogenesis imperfecta type 4 (Orphanet:216820), Osteogenesis imperfecta type 3 (Orphanet:216812)

HPO phenotypes

233 total (30 of 233 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000014	Abnormality of the bladder
HP:0000015	Bladder diverticulum
HP:0000023	Inguinal hernia
HP:0000025	Functional abnormality of male internal genitalia
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000075	Renal duplication
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000093	Proteinuria
HP:0000121	Nephrocalcinosis
HP:0000125	Pelvic kidney
HP:0000147	Polycystic ovaries
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000164	Abnormality of the dentition
HP:0000179	Thick lower lip vermilion
HP:0000212	Gingival overgrowth
HP:0000232	Everted lower lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000325	Triangular face

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001537_6	Immune reponse to smallpox (secreted IL-12p40)	3.000000e-07
GCST008839_115	Height	7.000000e-11
GCST90000025_585	Appendicular lean mass	3.000000e-12
GCST90002381_118	Eosinophil count	8.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0004980	appendicular lean mass
EFO:0004842	eosinophil count

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430
D010013	Osteogenesis Imperfecta	C05.116.099.708.685; C16.320.737; C17.300.200.540
C536044	Osteogenesis imperfecta, type 3 (supp.)
C565723	Williams-Beuren Region Duplication Syndrome (supp.)

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
Benzo(a)pyrene	increases expression, decreases expression, decreases methylation	3
Valproic Acid	affects expression, decreases expression, increases methylation	3
methylmercuric chloride	decreases expression	2
bisphenol A	decreases expression, increases expression	2
sodium arsenite	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
bisphenol F	increases expression	1
kojic acid	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	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
torcetrapib	increases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
LDN 193189	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Amiodarone	increases expression	1
Arsenicals	increases expression	1
Atrazine	increases expression	1
Doxorubicin	decreases expression	1
Gallic Acid	increases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2X4	Abcam HEK293T FKBP10 KO	Transformed cell line	Female
CVCL_D9WH	Ubigene HT-29 FKBP10 KO	Cancer cell line	Female
CVCL_E1XD	HAP1 FKBP10 (-) 1	Cancer cell line	Male
CVCL_E1XE	HAP1 FKBP10 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00131469	PHASE4	COMPLETED	Study of Teriparatide (FORTEO) to Treat Adults With Osteogenesis Imperfecta
NCT00159419	PHASE4	COMPLETED	Bisphosphonate Therapy for Osteogenesis Imperfecta
NCT01713231	PHASE4	COMPLETED	Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta
NCT02303873	PHASE4	COMPLETED	Efficacy and Safety of Alendronate in Chinese Children or Adolescents With Osteogenesis Imperfecta
NCT03735537	PHASE4	COMPLETED	Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid
NCT04152551	PHASE4	RECRUITING	Effects of Bisphosphonates on OI-Related Hearing Loss
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00001305	PHASE3	COMPLETED	Growth Hormone Therapy in Osteogenesis Imperfecta
NCT00005901	PHASE3	COMPLETED	Pamidronate to Treat Osteogenesis Imperfecta in Children
NCT00106028	PHASE3	COMPLETED	Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
NCT00982124	PHASE3	COMPLETED	An Efficacy and Safety Trial of Intravenous Zoledronic Acid in Infants Less Than One Year of Age, With Severe Osteogenesis Imperfecta
NCT02352753	PHASE3	TERMINATED	Multicenter,Single-arm Study to Evaluate Efficacy, Safety, & Pharmacokinetics of Denosumab in Children w/ OI
NCT03638128	PHASE3	TERMINATED	Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults With Osteogenesis Imperfecta
NCT05768854	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta
NCT05972551	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta
NCT06636071	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab in Pediatric Japanese Subjects With Osteogenesis Imperfecta
NCT07366086	PHASE3	RECRUITING	Pediatric Safety Follow-up Study of Prior Treatment With Romosozumab for Osteogenesis Imperfecta
NCT00975117	PHASE3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	PHASE3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	PHASE3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	PHASE3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	PHASE3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
NCT03118570	PHASE2	COMPLETED	A Study in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With BPS804
NCT00063479	PHASE2	COMPLETED	Bisphosphonate Treatment of Osteogenesis Imperfecta
NCT00131118	PHASE2	COMPLETED	Zoledronic Acid in Children (1 -17 Years) With Severe Osteogenesis Imperfecta
NCT01417091	PHASE2	COMPLETED	Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
NCT01679080	PHASE2	TERMINATED	The Effect of Treatment With Teriparatide and Zoledronic Acid in Patients With Osteogenesis Imperfecta
NCT01799798	PHASE2	COMPLETED	Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab
NCT03208582	PHASE2	COMPLETED	Do Bisphosphonates Alter the Skeletal Response to Mechanical Stimulation in Children With Osteogenesis Imperfecta?
NCT03216486	PHASE2	WITHDRAWN	An Exploratory Study of BPS804 Treatment in Adult Patients With Type I, III or IV Osteogenesis Imperfecta
NCT05312697	PHASE2	TERMINATED	Long-term Extension Study of Setrusumab in Adults With Type I, III, or IV Osteogenesis Imperfecta
NCT07062588	PHASE2	RECRUITING	Osteogenesis Imperfecta Trial of AGA2115 for ADUlts With COL1A1 and/or COL1A2 GeNetic Variations (IDUN)
NCT07557446	PHASE2	NOT_YET_RECRUITING	A Dose REgimen-Finding Study of AGA2115 in Chinese Patients With Osteogenesis ImpeRfecta (EIR)
NCT01880086	PHASE2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	PHASE2	COMPLETED	Males, Antioxidants, and Infertility Trial