FKBPL

Summary

FKBPL (FKBP prolyl isomerase like, HGNC:13949) is a protein-coding gene on chromosome 6p21.32, encoding FK506-binding protein-like (Q9UIM3). May be involved in response to X-ray.

The protein encoded by this gene has similarity to the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. The encoded protein is thought to have a potential role in the induced radioresistance. Also it appears to have some involvement in the control of the cell cycle.

Source: NCBI Gene 63943 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 44 total
• GTEx eGene: eQTL in 23 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.40 (unconstrained)
• MANE Select transcript: NM_022110

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13949
Approved symbol	FKBPL
Name	FKBP prolyl isomerase like
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	DIR1, NG7, WISp39
Ensembl gene	ENSG00000204315
Ensembl biotype	protein_coding
OMIM	617076
Entrez	63943

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

MANE Select: ENST00000375156

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000375156, ENST00000887777, ENST00000930347, ENST00000930348, ENST00000930349, ENST00000958763, ENST00001137398

RefSeq mRNA: 1 — MANE Select: NM_022110 NM_022110

CCDS: CCDS4738

Canonical transcript exons

ENST00000375156 — 2 exons

Exon	Start	End
ENSE00001864878	32130095	32130288
ENSE00001901420	32128707	32129854

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 85.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2412 / max 48.9123, expressed in 1459 samples.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, lower esophagus mucosa, esophagus mucosa, skin of leg.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FKBPL is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 23 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	5.0e-17	-0.28	6:32124066:G:A
Skin Not Sun Exposed Suprapubic	eqtl	5.5e-11	-0.34	6:32107027:T:C
Whole Blood	eqtl	1.4e-07	+0.28	6:32138237:C:A
Adipose Subcutaneous	eqtl	9.8e-07	-0.42	6:32130099:G:A
Artery Tibial	eqtl	1.4e-03	-0.31	6:32135890:G:A
Esophagus Mucosa	eqtl	1.5e-03	-0.18	6:32107027:T:C
Thyroid	eqtl	4.3e-03	+0.40	6:31586158:C:T
Artery Aorta	eqtl	4.9e-03	-0.32	6:32054075:A:G
Colon Transverse	eqtl	5.4e-03	+0.30	6:32077449:T:A
Brain Nucleus accumbens basal ganglia	eqtl	8.4e-03	-1.06	6:31269059:A:G
Breast Mammary Tissue	eqtl	8.5e-03	+0.35	6:31318286:TG:T
Heart Atrial Appendage	eqtl	1.1e-02	+0.36	6:32534309:C:T
Brain Caudate basal ganglia	eqtl	1.1e-02	-0.26	6:31872848:A:G
Lung	eqtl	1.4e-02	+0.19	6:32521955:T:A
Brain Substantia nigra	eqtl	1.5e-02	-1.81	6:32372007:A:C
Nerve Tibial	eqtl	1.8e-02	-0.14	6:31572652:C:G
Testis	eqtl	2.1e-02	+0.19	6:31308658:G:C
Adipose Visceral Omentum	eqtl	2.5e-02	+0.17	6:31472638:G:A
Cells Cultured fibroblasts	eqtl	2.6e-02	-0.46	6:31774118:T:C
Esophagus Muscularis	eqtl	2.7e-02	+0.28	6:32130114:A:G

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
72888	2.5391	1363
72887	0.7020	394

Top tissues by expression

showing 100 of 133 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.87	gold quality
lower esophagus mucosa	UBERON:0035834	82.42	gold quality
esophagus mucosa	UBERON:0002469	79.16	gold quality
skin of leg	UBERON:0001511	78.09	gold quality
zone of skin	UBERON:0000014	77.55	gold quality
granulocyte	CL:0000094	77.09	gold quality
skin of abdomen	UBERON:0001416	76.95	gold quality
mucosa of transverse colon	UBERON:0004991	76.89	gold quality
islet of Langerhans	UBERON:0000006	76.42	gold quality
apex of heart	UBERON:0002098	75.82	gold quality
body of stomach	UBERON:0001161	75.48	gold quality
esophagus	UBERON:0001043	75.34	gold quality
blood	UBERON:0000178	74.89	gold quality
stromal cell of endometrium	CL:0002255	74.75	gold quality
right adrenal gland	UBERON:0001233	74.57	gold quality
ventricular zone	UBERON:0003053	74.49	gold quality
fundus of stomach	UBERON:0001160	74.37	gold quality
right adrenal gland cortex	UBERON:0035827	74.30	gold quality
pancreas	UBERON:0001264	74.23	gold quality
gastrocnemius	UBERON:0001388	74.16	gold quality
ganglionic eminence	UBERON:0004023	74.12	gold quality
right lobe of thyroid gland	UBERON:0001119	74.08	gold quality
left lobe of thyroid gland	UBERON:0001120	73.86	gold quality
placenta	UBERON:0001987	73.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	73.72	gold quality
muscle of leg	UBERON:0001383	73.62	gold quality
body of pancreas	UBERON:0001150	73.58	gold quality
left adrenal gland	UBERON:0001234	73.56	gold quality
descending thoracic aorta	UBERON:0002345	73.56	gold quality
cortical plate	UBERON:0005343	73.49	gold quality
thyroid gland	UBERON:0002046	73.39	gold quality
smooth muscle tissue	UBERON:0001135	73.33	gold quality
left adrenal gland cortex	UBERON:0035825	73.19	gold quality
stomach	UBERON:0000945	73.05	gold quality
duodenum	UBERON:0002114	72.93	gold quality
Brodmann (1909) area 9	UBERON:0013540	72.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.60	gold quality
popliteal artery	UBERON:0002250	72.40	gold quality
tibial artery	UBERON:0007610	72.40	gold quality
right lobe of liver	UBERON:0001114	72.34	gold quality
rectum	UBERON:0001052	72.29	gold quality
fallopian tube	UBERON:0003889	72.21	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	72.20	gold quality
right coronary artery	UBERON:0001625	72.14	gold quality
vagina	UBERON:0000996	72.10	gold quality
transverse colon	UBERON:0001157	72.08	gold quality
left coronary artery	UBERON:0001626	72.07	gold quality
adrenal gland	UBERON:0002369	72.02	gold quality
lymph node	UBERON:0000029	71.96	gold quality
thoracic aorta	UBERON:0001515	71.94	gold quality
ascending aorta	UBERON:0001496	71.71	gold quality
leukocyte	CL:0000738	71.57	gold quality
muscle tissue	UBERON:0002385	71.55	gold quality
saliva-secreting gland	UBERON:0001044	71.51	gold quality
tonsil	UBERON:0002372	71.51	gold quality
muscle layer of sigmoid colon	UBERON:0035805	71.51	gold quality
lower esophagus	UBERON:0013473	71.47	gold quality
lower esophagus muscularis layer	UBERON:0035833	71.39	gold quality
colon	UBERON:0001155	71.29	gold quality
multicellular organism	UBERON:0000468	71.27	gold quality
superior frontal gyrus	UBERON:0002661	71.25	gold quality
right frontal lobe	UBERON:0002810	71.14	gold quality
spleen	UBERON:0002106	71.06	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	71.06	gold quality
monocyte	CL:0000576	70.98	gold quality
gall bladder	UBERON:0002110	70.98	gold quality
minor salivary gland	UBERON:0001830	70.91	gold quality
vermiform appendix	UBERON:0001154	70.77	gold quality
heart left ventricle	UBERON:0002084	70.62	gold quality
ectocervix	UBERON:0012249	70.54	gold quality
intestine	UBERON:0000160	70.44	gold quality
skeletal muscle tissue	UBERON:0001134	70.26	gold quality
primary visual cortex	UBERON:0002436	70.20	gold quality
anterior cingulate cortex	UBERON:0009835	70.17	gold quality
adult mammalian kidney	UBERON:0000082	70.15	gold quality
myometrium	UBERON:0001296	70.00	gold quality
metanephros cortex	UBERON:0010533	69.94	gold quality
adipose tissue	UBERON:0001013	69.90	gold quality
omental fat pad	UBERON:0010414	69.88	gold quality
subcutaneous adipose tissue	UBERON:0002190	69.82	gold quality
uterine cervix	UBERON:0000002	69.49	gold quality
heart	UBERON:0000948	69.36	gold quality
thoracic mammary gland	UBERON:0005200	69.34	gold quality
liver	UBERON:0002107	69.28	gold quality
left uterine tube	UBERON:0001303	69.26	gold quality
endocervix	UBERON:0000458	69.24	gold quality
bone marrow	UBERON:0002371	69.19	gold quality
testis	UBERON:0000473	69.16	gold quality
cerebral cortex	UBERON:0000956	69.12	gold quality
small intestine	UBERON:0002108	69.07	gold quality
small intestine Peyer’s patch	UBERON:0003454	69.06	gold quality
left testis	UBERON:0004533	68.95	gold quality
body of uterus	UBERON:0009853	68.92	gold quality
urinary bladder	UBERON:0001255	68.86	gold quality
cortex of kidney	UBERON:0001225	68.79	gold quality
right testis	UBERON:0004534	68.66	gold quality
kidney	UBERON:0002113	68.42	gold quality
right uterine tube	UBERON:0001302	68.41	gold quality
substantia nigra	UBERON:0002038	68.38	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.90

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	12.7
Caudate putamen	tissue	12.1
Skin 1	tissue	7.7	low
Salivary gland	tissue	6.0	not detected
Epididymis	tissue	5.7	medium
Thymus	tissue	5.1
Vagina	tissue	4.9	not detected
Stomach 1	tissue	4.6	medium
Cerebral cortex	tissue	4.5	low
Somatosensory cortex	tissue	4.5
Cerebellum	tissue	4.1	not detected
Fallopian tube	tissue	4.1	low
Pons	tissue	4.0
Tongue	tissue	4.0
Midbrain	tissue	4.0
Thalamus	tissue	4.0
Thyroid gland	tissue	4.0	medium
Superior colliculi	tissue	3.9
Breast	tissue	3.8	medium
Parathyroid gland	tissue	3.8	not detected
Occipital cortex	tissue	3.8
Periaqueductal gray	tissue	3.7
Hippocampal formation	tissue	3.6
Retrosplenial and cingulate cortex	tissue	3.6
Prefrontal cortex	tissue	3.5
Ovary	tissue	3.5	low
Medulla oblongata	tissue	3.5
Hypothalamus	tissue	3.5
Temporal cortex	tissue	3.5
Smooth muscle	tissue	3.4	low
Motor cortex	tissue	3.4
Spinal cord	tissue	3.4
Retrosplenial cortex	tissue	3.4
Putamen	tissue	3.3
Amygdala	tissue	3.3
Rectum	tissue	3.2	low
Basal ganglia	tissue	3.2	medium
Substantia nigra	tissue	3.2
Liver	tissue	3.2	medium
Corpus callosum	tissue	3.2
Septum	tissue	3.2
Pancreas	tissue	3.1	low
Entorhinal cortex	tissue	3.1
Ventral forebrain	tissue	3.1
Olfactory bulb	tissue	3.1
Insular cortex	tissue	3.1
Lung	tissue	3.0	low
Small intestine	tissue	3.0	high
Pituitary gland	tissue	2.9
Lymph node	tissue	2.9	not detected
Colon	tissue	2.8	medium
Skeletal muscle	tissue	2.6	low
Spleen	tissue	2.6	not detected
Bone marrow	tissue	2.6	not detected
Testis	tissue	2.5	high
Kidney	tissue	2.4	medium
Adrenal gland	tissue	2.4	medium
Hippocampus	tissue	2.0	low
Prostate	tissue	2.0	low
Appendix	tissue	1.9	low

Brain sub-regions (HPA Brain Atlas): detected in 187; highest nTPM — Angular gyrus (white matter) (4.2), Blood vessel (3.7), Dorsal hippocampus (3.6), Ventral spinal cord (3.4), White matter (3.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

Functional genomics

gnomAD constraint: pLI 1.62e-11, LOEUF 1.4, missense Z 1.69 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000375156 — one region, missense o/e 0.83.

Literature-anchored findings (GeneRIF, showing 16)

• Results demonstrate the importance of posttranslational stabilization of p21 protein by WISp39 in regulating cellular p21 activity. (PMID:15664193)
• FKBPL can be classed as a new member of the FKBP protein family with a role in steroid receptor complexes and signaling. (PMID:18669603)
• Findings suggest that FKBPL may have prognostic value based on its impact on tumor proliferative capacity and sensitivity to endocrine therapies, which improve outcome. (PMID:20103631)
• Alterations in the gene for FKBPL in azoospermic patients. (PMID:20210997)
• Genome-wide association study of age-related macular degeneration identifies TNXB, FKBPL and NOTCH4 as candidate susceptibility genes. (PMID:22694956)
• FKBPL and and its peptide derivative, AD-01 regulate expression of CD44. (PMID:23457460)
• high levels of FKBPL and RBCK1 correlated with increased patient survival, whereas high RBCK1 predicted for a poor response to tamoxifen. (PMID:23912458)
• FKBPL is an important regulator of developmental and pathological angiogenesis. (PMID:25767277)
• WISp39 preferentially interacts with phosphorylated Coronin 1B, allowing it to complex with Slingshot phosphatase to dephosphorylate and activate Cofilin. (PMID:25800056)
• The data suggests a role for FKBPL as a prognostic factor for BCSS, with the potential to be routinely evaluated within the clinic. (PMID:25906750)
• This study identified two low-frequency nonsynonymous variants at FKBPL (rs200847762, OR = 0.34, 95% CI = 0.20-0.57, P = 4.31 x 10-5) and ARPC1B (rs1045012, OR = 0.56, 95% CI = 0.43-0.74, P = 4.30 x 10-5) associated with breast cancer risk. (PMID:27479355)
• Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment. (PMID:32617576)
• FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function. (PMID:34149611)
• A novel mutation in FK506 binding protein-like (FKBPL) causes male infertility. (PMID:34212559)
• Loss of Expression of Antiangiogenic Protein FKBPL in Endometrioid Endometrial Carcinoma: Implications for Clinical Practice. (PMID:36295491)
• FK506-Binding Protein like (FKBPL) Has an Important Role in Heart Failure with Preserved Ejection Fraction Pathogenesis with Potential Diagnostic Utility. (PMID:36830764)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	fkbpl	ENSDARG00000095322
mus_musculus	Fkbpl	ENSMUSG00000033739
rattus_norvegicus	Fkbpl	ENSRNOG00000000432
caenorhabditis_elegans	fkb-2	WBGENE00001427
caenorhabditis_elegans		WBGENE00001429
caenorhabditis_elegans	fkb-5	WBGENE00001430
caenorhabditis_elegans	fkb-8	WBGENE00001433

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), FKBP2 (ENSG00000173486), TTC9B (ENSG00000174521), FKBP1C (ENSG00000198225)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1932127) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal blood vessel physiology	1
abnormal vascular branching morphogenesis	1
increased tumor growth/size	1
increased angiogenesis	1
increased susceptibility to induced morbidity/mortality	1
abnormal tumor vascularization	1
embryonic lethality, complete penetrance	1
preweaning lethality, complete penetrance	1
abnormal intersomitic vessel morphology	1
embryonic lethality prior to organogenesis	1
embryonic lethality prior to tooth bud stage	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RAP0	98.6%	Diamond
Pan paniscus	Q95MN9	98.5%	Diamond
Chlorocebus aethiops	O97628	98.2%	Diamond
Xenopus tropicalis	Q28IV3	86.2%	Diamond
Xenopus laevis	Q6NU95	86.2%	Diamond
Zea mays	K7TQE3	44.7%	Diamond
Arabidopsis thaliana	Q9LDC0	40.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PPT2-EGFL8	ncRNA	100532746
MIR6721	ncRNA	102466190
AGPAT1	protein-coding	10554
ATF6B	protein-coding	1388
PRRT1	protein-coding	80863
EGFL8	protein-coding	80864
PPT2	protein-coding	9374
MIR6833	ncRNA	102465500
RNF5	protein-coding	6048
CYP21A2	protein-coding	1589
TNXB	protein-coding	7148
C4B	protein-coding	721

Protein

Protein identifiers

FK506-binding protein-like — Q9UIM3 (reviewed: Q9UIM3)

Alternative names: WAF-1/CIP1 stabilizing protein 39

All UniProt accessions (2): A0A024RCQ6, Q9UIM3

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in response to X-ray. Regulates p21 protein stability by binding to Hsp90 and p21.

Subunit / interactions. Forms a ternary complex with CDKN1A/p21 and HSP90AB1/Hsp90.

Tissue specificity. Ubiquitously expressed with higher levels in testis.

RefSeq proteins (1): NP_071393* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR050754	FKBP4/5/8-like	Family

Pfam: PF00515, PF13432

UniProt features (10 total): repeat 3, mutagenesis site 2, chain 1, region of interest 1, modified residue 1, sequence variant 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UIM3-F1	77.00	0.53

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; mitotic spindle

Antibody reliability (HPA): IH approved · IF approved

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 (1)

Type	Positions
Phosphothreonine	3

Mutagenesis-validated functional residues (2)

Position	Phenotype
287	abolishes hsp90ab1 binding; when associated with a-291.
291	abolishes hsp90ab1 binding; when associated with a-287.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-8852276	The role of GTSE1 in G2/M progression after G2 checkpoint	curated
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-69275	G2/M Transition	—
R-HSA-453274	Mitotic G2-G2/M phases	—

MSigDB gene sets: 135 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, MARTINEZ_RB1_TARGETS_UP, DOANE_RESPONSE_TO_ANDROGEN_DN, GOBP_BLOOD_VESSEL_MORPHOGENESIS, GOBP_RESPONSE_TO_RADIATION, CYTAGCAAY_UNKNOWN, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, FISCHER_DREAM_TARGETS, GOBP_BRANCHING_MORPHOGENESIS_OF_AN_EPITHELIAL_TUBE, GOBP_TISSUE_MORPHOGENESIS, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT

GO Biological Process (1): response to radiation (GO:0009314)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), cytosol (GO:0005829)

Reactome top-level categories

4 top-level categories:

Category	Pathways
G2/M Transition	1
Cell Cycle, Mitotic	1
Mitotic G2-G2/M phases	1
Cell Cycle	1

GO top-level categories

4 GO namespaces:

Category	Terms
cellular anatomical structure	2
response to abiotic stimulus	1
binding	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 4 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
extracellular region	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 800 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FKBPL	ST13	P50502	457
FKBPL	MBOAT1	Q6ZNC8	457
FKBPL	TEDC2	Q7L2K0	448
FKBPL	MMRN2	Q9H8L6	448
FKBPL	ISM1	B1AKI9	445
FKBPL	TERB2	Q8NHR7	445
FKBPL	TERB1	Q8NA31	442
FKBPL	ZSWIM7	Q19AV6	441
FKBPL	ATF6B	Q99941	441
FKBPL	EGFL8	Q99944	430
FKBPL	FKBP15	Q5T1M5	421
FKBPL	MSH5	O43196	415
FKBPL	TDRKH	Q9Y2W6	414
FKBPL	RALA	P11233	412
FKBPL	AVPR2	P30518	409

IntAct

Human interaction partners of FKBPL in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 47 partners by confidence:

Partner	Interaction type	MIscore	Records
ANKRD49	physical association	0.860	4
CALCOCO2	physical association	0.560	3
BRAF	association	0.530	1
AAR2	physical association	0.400	1
BAG2	physical association	0.400	1
CFLAR	physical association	0.400	1
CYFIP1	physical association	0.400	1
DNM3	physical association	0.400	1
EFTUD2	physical association	0.400	1
EIPR1	physical association	0.400	1
ETF1	physical association	0.400	1
FBXO24	physical association	0.400	1
FBXW2	physical association	0.400	1
G7	physical association	0.400	1
GET4	physical association	0.400	1
GNA15	physical association	0.400	1
GNAZ	physical association	0.400	1
GNB2	physical association	0.400	1
GNB4	physical association	0.400	1
GTF3C5	physical association	0.400	1
HSPA2	physical association	0.400	1
HUS1B	physical association	0.400	1
IRS4	physical association	0.400	1
KAT5	physical association	0.400	1
KEAP1	physical association	0.400	1
MAOA	physical association	0.400	1
MAP3K8	physical association	0.400	1
MATR3	physical association	0.400	1
MLF1	physical association	0.400	1
MOS	physical association	0.400	1

BioGRID (67 interactions; top human partners by supporting records): ANKRD49 (Affinity Capture-MS; 6 records), HSP90AA1 (Affinity Capture-Western; 6 records), RBCK1 (Affinity Capture-MS; 5 records), CDC37 (Affinity Capture-Luminescence; 4 records), CDKN1A (Reconstituted Complex; 3 records), CSNK1D (Affinity Capture-MS; 3 records), CSNK1E (Affinity Capture-MS; 3 records), AHSA1 (Affinity Capture-Luminescence; 2 records), BRAF (Affinity Capture-MS; 2 records), EDRF1 (Affinity Capture-MS; 2 records), ESR1 (Affinity Capture-Western; 2 records), HSP90AB1 (Affinity Capture-Luminescence; 2 records), NADSYN1 (Affinity Capture-MS; 2 records), PLS1 (Affinity Capture-MS; 2 records), RNF31 (Affinity Capture-MS; 2 records)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ CIP1-FKBPL-HSP90 complex	3	CDKN1A, FKBPL, HSP90AA1

Disease & clinical

Genetic variants

Variant evidence for FKBPL: 44 ClinVar records (0 pathogenic / likely pathogenic); 22 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	6
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 14 predictions of 49):

Position(s)	Effect	Δscore	Sites
6:32129855	acceptor_loss	0.9900
6:32130039	donor_gain	0.9800
6:32129855	acceptor_loss	0.9700
6:32130093–32130094	donor_loss	0.9700	5
6:32130093	donor_loss	0.9600
6:32129856	acceptor_loss	0.9400
6:32129856	acceptor_loss	0.9300
6:32130095	donor_loss	0.9300
6:32130095	donor_loss	0.9100
6:32130115	donor_gain	0.9100

AlphaMissense

383 missense substitutions predicted likely pathogenic (of 2,230 scored), across 129 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F348	8	0.900	0.986
F104	8	0.812	0.961
N319	8	0.751	0.933
F221	7	0.907	0.955
W199	7	0.901	0.963
F192	7	0.893	0.986
C124	7	0.861	0.975
E171	7	0.861	0.964
N257	7	0.841	0.945
M347	7	0.829	0.964
W97	7	0.816	0.904
D308	7	0.773	0.828
K106	6	0.916	0.989
P118	6	0.916	0.992
M167	6	0.899	0.923
K287	6	0.893	0.974
C261	6	0.843	0.982
K117	6	0.833	0.951
G112	6	0.818	0.919
K206	6	0.788	0.929

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	0.000689
Uterine Corpus Endometrial Carcinoma (TCGA)	favorable	0.000961

Disease associations

OMIM: gene MIM:617076 | disease phenotypes:

GWAS associations

22 associations:

Study	Trait	p-value
GCST004133_55	Ulcerative colitis	5e-65
GCST004131_25	Inflammatory bowel disease	2e-31
GCST004521_71	Autism spectrum disorder or schizophrenia	6e-18
GCST004521_265	Autism spectrum disorder or schizophrenia	3e-17
GCST004521_214	Autism spectrum disorder or schizophrenia	2e-16
GCST004521_85	Autism spectrum disorder or schizophrenia	5e-16
GCST004521_268	Autism spectrum disorder or schizophrenia	3e-15
GCST004521_269	Autism spectrum disorder or schizophrenia	3e-15
GCST004521_87	Autism spectrum disorder or schizophrenia	5e-15
GCST004521_220	Autism spectrum disorder or schizophrenia	1e-14
GCST004521_121	Autism spectrum disorder or schizophrenia	4e-14
GCST004521_124	Autism spectrum disorder or schizophrenia	4e-14
GCST004521_89	Autism spectrum disorder or schizophrenia	5e-13
GCST004521_168	Autism spectrum disorder or schizophrenia	2e-12
GCST004521_127	Autism spectrum disorder or schizophrenia	4e-12
GCST005830_73	Hand grip strength	4e-11
GCST004521_177	Autism spectrum disorder or schizophrenia	2e-10
GCST005580_145	Intraocular pressure	3e-10
GCST003450_2	Clozapine-induced agranulocytosis/granulocytopenia in treatment-resistant schizophrenia	3e-9
GCST001942_21	Prostate cancer	5e-9
GCST004521_105	Autism spectrum disorder or schizophrenia	3e-8
GCST005542_1	Sarcoidosis (non-Lofgren’s syndrome without extrapulmonary manifestations)	7e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0006941	grip strength measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Peptidyl-prolyl cis/trans isomerases

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	increases expression	1
sodium arsenite	decreases expression	1
manganese chloride	increases expression, increases abundance	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
jinfukang	increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Fulvestrant	increases response to substance	1
Leflunomide	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases expression	1
Coumestrol	increases expression	1
Cyclophosphamide	increases expression	1
Estradiol	decreases reaction, increases phosphorylation	1
Fluorouracil	increases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tamoxifen	decreases reaction, increases phosphorylation, increases response to substance	1
Urethane	increases expression	1
Epirubicin	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.