FKBP1C

Summary

FKBP1C (FKBP prolyl isomerase family member 1C, HGNC:21376) is a protein-coding gene on chromosome 6q12, encoding Peptidyl-prolyl cis-trans isomerase FKBP1C (Q5VVH2). Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.

Predicted to enable peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in negative regulation of activin receptor signaling pathway and negative regulation of transforming growth factor beta receptor signaling pathway. Predicted to be active in sarcoplasmic reticulum membrane.

Source: NCBI Gene 642489 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001395980

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21376
Approved symbol	FKBP1C
Name	FKBP prolyl isomerase family member 1C
Location	6q12
Locus type	gene with protein product
Status	Approved
Aliases	bA184C23.2
Ensembl gene	ENSG00000198225
Ensembl biotype	protein_coding
Entrez	642489

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000370659

RefSeq mRNA: 1 — MANE Select: NM_001395980 NM_001395980

CCDS: CCDS93938

Canonical transcript exons

ENST00000370659 — 1 exons

Exon	Start	End
ENSE00001453252	63211469	63213027

Expression profiles

Bgee: expression breadth broad, 38 present calls, max score 76.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.9854 / max 135.2625, expressed in 1786 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68349	7.4663	1756
68350	3.5191	1336

Top tissues by expression

92 total, 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	76.93	gold quality
stromal cell of endometrium	CL:0002255	56.27	gold quality
cortical plate	UBERON:0005343	53.81	gold quality
ganglionic eminence	UBERON:0004023	49.10	silver quality
placenta	UBERON:0001987	48.26	gold quality
bone marrow cell	CL:0002092	48.12	gold quality
vermiform appendix	UBERON:0001154	47.10	gold quality
sural nerve	UBERON:0015488	42.65	gold quality
blood	UBERON:0000178	42.51	silver quality
colonic epithelium	UBERON:0000397	41.24	gold quality
skeletal muscle tissue	UBERON:0001134	40.92	gold quality
ventricular zone	UBERON:0003053	40.50	silver quality
muscle tissue	UBERON:0002385	40.32	gold quality
bone marrow	UBERON:0002371	40.23	gold quality
islet of Langerhans	UBERON:0000006	39.22	silver quality
prefrontal cortex	UBERON:0000451	39.18	gold quality
mucosa of transverse colon	UBERON:0004991	39.04	silver quality
leukocyte	CL:0000738	38.46	gold quality
monocyte	CL:0000576	38.13	gold quality
omental fat pad	UBERON:0010414	36.82	silver quality
endometrium	UBERON:0001295	36.69	silver quality
lung	UBERON:0002048	36.65	gold quality
mucosa of stomach	UBERON:0001199	36.32	silver quality
upper lobe of left lung	UBERON:0008952	36.11	silver quality
apex of heart	UBERON:0002098	36.04	gold quality
adipose tissue	UBERON:0001013	35.69	gold quality
nucleus accumbens	UBERON:0001882	35.58	silver quality
liver	UBERON:0002107	35.57	gold quality
lymph node	UBERON:0000029	35.45	silver quality
muscle of leg	UBERON:0001383	35.03	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	24.19

Regulation

Is transcription factor: no

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fkbp1a	ENSMUSG00000032966
rattus_norvegicus	Fkbp1a	ENSRNOG00000008822
drosophila_melanogaster	Fkbp12	FBGN0013954
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), FKBP10 (ENSG00000141756), TTC9C (ENSG00000162222), FKBP2 (ENSG00000173486), TTC9B (ENSG00000174521), FKBPL (ENSG00000204315)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase FKBP1C — Q5VVH2 (reviewed: Q5VVH2)

All UniProt accessions (1): Q5VVH2

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.

Similarity. Belongs to the FKBP-type PPIase family. FKBP1 subfamily.

RefSeq proteins (1): NP_001382909* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001179	PPIase_FKBP_dom	Domain
IPR046357	PPIase_dom_sf	Homologous_superfamily
IPR050689	FKBP-type_PPIase	Family

Pfam: PF00254

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (2 total): chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VVH2-F1	95.12	0.97

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 55 (showing top): GOBP_CIRCULATORY_SYSTEM_PROCESS, chr6q12, GOBP_REGULATION_OF_CARDIAC_MUSCLE_CONTRACTION_BY_REGULATION_OF_THE_RELEASE_OF_SEQUESTERED_CALCIUM_ION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_STRIATED_MUSCLE_CONTRACTION, GOBP_PROTEIN_MATURATION, GOBP_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_MUSCLE_CONTRACTION, GOBP_REGULATION_OF_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_CARDIAC_MUSCLE_CONTRACTION_BY_CALCIUM_ION_SIGNALING, GOBP_MAINTENANCE_OF_LOCATION, GOBP_PROTEIN_FOLDING, GOBP_SARCOPLASMIC_RETICULUM_CALCIUM_ION_TRANSPORT, GOBP_REGULATION_OF_SYSTEM_PROCESS, GOBP_MONOATOMIC_ION_HOMEOSTASIS

GO Biological Process (1): regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion (GO:0010881)

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

GO Cellular Component (1): sarcoplasmic reticulum membrane (GO:0033017)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of cardiac muscle contraction by calcium ion signaling	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
endoplasmic reticulum membrane	1
sarcoplasmic reticulum	1
bounding membrane of organelle	1

Protein interactions and networks

STRING

2140 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FKBP1C	PPIA	P05092	732
FKBP1C	ATCAY	Q86WG3	708
FKBP1C	PIN1	Q13526	672
FKBP1C	HSP90AA1	P07900	589
FKBP1C	HSP90AB1	P08238	584
FKBP1C	PPIF	P30405	546
FKBP1C	PPIB	P23284	516
FKBP1C	HSPD1	P10809	507
FKBP1C	SSU72	Q9NP77	501
FKBP1C	POT1	Q9NUX5	493
FKBP1C	PFN1	P07737	444
FKBP1C	MAPK8	P45983	437
FKBP1C	PFN4	Q8NHR9	435
FKBP1C	PFN3	P60673	434
FKBP1C	TINF2	Q9BSI4	430

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: O04287, O42123, O42993, O94746, P0A0W2, P0A0W3, P0C1J3, P0CP94, P0CP95, P0CY37, P18203, P20080, P20081, P26883, P28725, P28870, P48375, P56989, P62942, P62943, P68106, P68107, P97534, Q13526, Q2U316, Q2UPT7, Q38931, Q43207, Q4HZB8, Q4R383, Q4W9R2, Q4WHX4, Q4WLV6, Q554J3, Q5ATN7, Q5BIN5, Q5VVH2, Q62658, Q6BX45, Q6CF41

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

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

167 predictions. Top by Δscore:

Variant	Effect	Δscore
6:63211658:A:T	donor_gain	0.8800
6:63211643:G:T	donor_gain	0.7600
6:63211719:G:GT	donor_gain	0.7600
6:63211629:A:AG	donor_gain	0.7000
6:63211607:G:GT	donor_gain	0.6600
6:63211499:T:TA	donor_gain	0.6500
6:63211657:G:GT	donor_gain	0.6500
6:63211560:G:GT	donor_gain	0.6300
6:63211643:G:GT	donor_gain	0.6300
6:63211712:C:T	donor_gain	0.6300
6:63211589:A:T	donor_gain	0.6000
6:63211696:T:G	donor_gain	0.6000
6:63211755:A:G	donor_gain	0.5900
6:63211696:T:TG	donor_gain	0.5700
6:63211707:C:G	donor_gain	0.5600
6:63211654:A:G	donor_gain	0.5500
6:63212791:A:AC	acceptor_gain	0.5400
6:63211560:G:T	donor_gain	0.5300
6:63211588:G:GT	donor_gain	0.5100
6:63211650:G:GT	donor_gain	0.5100
6:63211642:G:GT	donor_gain	0.5000
6:63211657:G:T	donor_gain	0.5000
6:63211725:A:AG	donor_gain	0.4900
6:63211680:G:T	donor_gain	0.4800
6:63211681:A:T	donor_gain	0.4800
6:63211653:G:GT	donor_gain	0.4600
6:63211662:A:T	donor_gain	0.4500
6:63211680:G:GT	donor_gain	0.4500
6:63211759:GT:G	donor_gain	0.4500
6:63212721:A:C	acceptor_gain	0.4100

AlphaMissense

707 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:63211854:T:C	F100L	0.911
6:63211856:C:A	F100L	0.911
6:63211856:C:G	F100L	0.911
6:63211665:T:C	F37L	0.906
6:63211667:T:A	F37L	0.906
6:63211667:T:G	F37L	0.906
6:63211701:T:C	F49L	0.896
6:63211703:T:A	F49L	0.896
6:63211703:T:G	F49L	0.896
6:63211734:T:A	W60R	0.873
6:63211734:T:C	W60R	0.873
6:63211773:G:C	A73P	0.844
6:63211602:T:C	F16L	0.839
6:63211604:C:A	F16L	0.839
6:63211604:C:G	F16L	0.839
6:63211786:T:A	I77K	0.825
6:63211671:T:C	S39P	0.812
6:63211768:A:C	Q71P	0.806
6:63211675:C:T	S40F	0.801
6:63211736:G:C	W60C	0.784
6:63211736:G:T	W60C	0.784
6:63211695:T:C	F47L	0.782
6:63211697:T:A	F47L	0.782
6:63211697:T:G	F47L	0.782
6:63211801:C:A	A82D	0.766
6:63211735:G:C	W60S	0.765
6:63211849:T:A	L98H	0.763
6:63211731:G:C	G59R	0.760
6:63211842:G:C	A96P	0.758
6:63211756:T:C	M67T	0.756

dbSNP variants (sampled 300 via entrez): RS1000111240 (6:63211505 T>C), RS1001772937 (6:63211868 T>G), RS1002105023 (6:63213185 T>G), RS1003487473 (6:63211079 A>G), RS1006530164 (6:63213390 G>A), RS1007943276 (6:63210392 A>C), RS1008691938 (6:63211267 C>G,T), RS1008774751 (6:63210996 C>T), RS1009195949 (6:63213126 T>C), RS1011262435 (6:63213293 T>C), RS1011718948 (6:63210014 T>A,C,G), RS1013039093 (6:63210587 C>A), RS1013171068 (6:63209557 C>A), RS1015052533 (6:63211951 C>A,G,T), RS1015862383 (6:63213486 A>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008762_7	Intake of sweets	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010158	sugar consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
chloropicrin	affects expression, decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
lead acetate	decreases expression	1
ICG 001	decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases 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	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Tunicamycin	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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