PPIG

Summary

PPIG (peptidylprolyl isomerase G, HGNC:14650) is a protein-coding gene on chromosome 2q31.1, encoding Peptidyl-prolyl cis-trans isomerase G (Q13427). PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding.

Enables peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in protein folding. Located in cytosol and nuclear speck.

Source: NCBI Gene 9360 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 98 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004792

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14650
Approved symbol	PPIG
Name	peptidylprolyl isomerase G
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	CARS-Cyp, SRCyp, SCAF10
Ensembl gene	ENSG00000138398
Ensembl biotype	protein_coding
OMIM	606093
Entrez	9360

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 23 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000260970, ENST00000409714, ENST00000414307, ENST00000417938, ENST00000433207, ENST00000448752, ENST00000462903, ENST00000466142, ENST00000482772, ENST00000530152, ENST00000676508, ENST00000676557, ENST00000676756, ENST00000677392, ENST00000677750, ENST00000678088, ENST00000678499, ENST00000678638, ENST00000678695, ENST00000678721, ENST00000679107, ENST00000679324, ENST00000898369, ENST00000935436, ENST00000935437, ENST00000935438, ENST00000935439, ENST00000935440, ENST00000935441, ENST00000951876, ENST00000951877, ENST00000951878, ENST00000951879

RefSeq mRNA: 1 — MANE Select: NM_004792 NM_004792

CCDS: CCDS2235

Canonical transcript exons

ENST00000260970 — 14 exons

Exon	Start	End
ENSE00001016132	169630774	169630987
ENSE00001368659	169603642	169603694
ENSE00001387482	169584351	169584490
ENSE00001824624	169636413	169641406
ENSE00003484674	169614464	169614493
ENSE00003497241	169631766	169631933
ENSE00003514722	169633160	169633247
ENSE00003522833	169604026	169604102
ENSE00003525873	169614585	169614724
ENSE00003531513	169606039	169606146
ENSE00003564635	169608671	169608758
ENSE00003592419	169604187	169604261
ENSE00003621978	169636092	169636228
ENSE00003680265	169607104	169607148

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 98.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.1846 / max 2956.8445, expressed in 1817 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23551	25.7119	1796
23554	15.5062	1735
23552	3.4385	1232
23553	2.5280	1251

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.43	gold quality
secondary oocyte	CL:0000655	98.07	gold quality
calcaneal tendon	UBERON:0003701	98.00	gold quality
oocyte	CL:0000023	97.97	gold quality
tendon	UBERON:0000043	97.88	gold quality
medial globus pallidus	UBERON:0002477	97.48	gold quality
tendon of biceps brachii	UBERON:0008188	97.37	gold quality
globus pallidus	UBERON:0001875	97.09	gold quality
superficial temporal artery	UBERON:0001614	96.74	gold quality
caput epididymis	UBERON:0004358	96.59	gold quality
pylorus	UBERON:0001166	96.56	gold quality
mammary duct	UBERON:0001765	96.49	gold quality
cauda epididymis	UBERON:0004360	96.38	gold quality
colonic epithelium	UBERON:0000397	96.26	gold quality
lateral globus pallidus	UBERON:0002476	95.97	gold quality
saphenous vein	UBERON:0007318	95.81	gold quality
epithelium of mammary gland	UBERON:0003244	95.78	gold quality
corpus epididymis	UBERON:0004359	95.76	gold quality
superior surface of tongue	UBERON:0007371	95.75	gold quality
renal medulla	UBERON:0000362	95.65	gold quality
cardia of stomach	UBERON:0001162	95.63	gold quality
urethra	UBERON:0000057	95.59	gold quality
pericardium	UBERON:0002407	95.53	gold quality
monocyte	CL:0000576	95.47	gold quality
seminal vesicle	UBERON:0000998	95.44	gold quality
blood vessel layer	UBERON:0004797	95.30	gold quality
pons	UBERON:0000988	95.29	gold quality
cranial nerve II	UBERON:0000941	95.27	gold quality
inferior vagus X ganglion	UBERON:0005363	95.20	gold quality
mononuclear cell	CL:0000842	95.06	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-31	yes	1884.87
E-MTAB-6379	no	2394.61
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, HHEX, HNF4A, MAX, MYB, NFKB1, NR1H3, NR1H4, NR1I3, NR3C1, PITX2, RELA, SOX17, STAT5B, TBX4, TCF3

miRNA regulators (miRDB)

33 targeting PPIG, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-374B-3P	98.63	68.24	1360
HSA-MIR-12125	98.59	67.54	1044

Literature-anchored findings (GeneRIF, showing 4)

• human nuclear SRcyp is a cell cycle-regulated cyclophilin (PMID:15016823)
• Results show that SR-cyclophilin interacts and colocalizes with nuclear pinin, a SR-related protein involved in pre-mRNA splicing. (PMID:15358154)
• The finding that zebularine upregulates CYP gene expression through DNMT1 and PKR modulation sheds light on the mechanisms controlling hepatocyte function and thus may aid in the development of new in-vitro systems using high-functioning hepatocytes (PMID:28112215)
• results indicate that LUC7L3, PPIG, and SFRS18 are not only implicated in EDA+ fibronectin formation, but also that they could possess multiple roles in psoriasis-associated molecular abnormalities. (PMID:28589370)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppig	ENSDARG00000044431
mus_musculus	Ppig	ENSMUSG00000042133
rattus_norvegicus	Ppig	ENSRNOG00000007673
drosophila_melanogaster	Cyp40	FBGN0036020
drosophila_melanogaster	Moca-cyp	FBGN0039581
caenorhabditis_elegans		WBGENE00000885

Paralogs (22): PPIE (ENSG00000084072), PPIL2 (ENSG00000100023), PPIF (ENSG00000108179), PPWD1 (ENSG00000113593), NKTR (ENSG00000114857), PPIL4 (ENSG00000131013), PPIL1 (ENSG00000137168), CWC27 (ENSG00000153015), PPIB (ENSG00000166794), PPIC (ENSG00000168938), PPID (ENSG00000171497), PPIH (ENSG00000171960), PPIL6 (ENSG00000185250), PPIA (ENSG00000196262), PPIAL4G (ENSG00000236334), PPIL3 (ENSG00000240344), PPIAL4A (ENSG00000263353), PPIAL4H (ENSG00000270339), PPIAL4E (ENSG00000271567), PPIAL4F (ENSG00000279782), PPIAL4C (ENSG00000288867), PPIAL4D (ENSG00000289549)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase G — Q13427 (reviewed: Q13427)

Alternative names: CASP10, Clk-associating RS-cyclophilin, Cyclophilin G, Rotamase G

All UniProt accessions (10): Q13427, A0A7I2V2U3, A0A7I2V4F2, A0A7I2V4W3, A0A7I2V5Q5, A0A7I2V629, C9J679, C9JM79, C9JN15, E9PG73

UniProt curated annotations — full annotation on UniProt →

Function. PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding. May be implicated in the folding, transport, and assembly of proteins. May play an important role in the regulation of pre-mRNA splicing.

Subunit / interactions. Interacts with CLK1, PNN and with the phosphorylated C-terminal domain of RNA polymerase II.

Subcellular location. Nucleus matrix. Nucleus speckle.

Tissue specificity. Ubiquitous.

Activity regulation. Inhibited by cyclosporin A (CsA).

Domain organisation. The RS domain is required for the interaction with the phosphorylated C-terminal domain of RNA polymerase II.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13427-1	1	yes
Q13427-2	2

RefSeq proteins (1): NP_004783* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002130	Cyclophilin-type_PPIase_dom	Domain
IPR020892	Cyclophilin-type_PPIase_CS	Conserved_site
IPR029000	Cyclophilin-like_dom_sf	Homologous_superfamily

Pfam: PF00160

Enzyme classification (BRENDA):

• EC 5.2.1.8 — peptidylprolyl isomerase (BRENDA: 69 organisms, 374 substrates, 222 inhibitors, 24 Km, 30 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-SUCCINYL-ALA-GLU-(TRANS)-PRO-PHE-4-NITROANILID	0.17–0.7	5
N-SUCCINYL-ALA-ALA-(CIS)-PRO-PHE-4-NITROANILIDE	0.104–0.814	2
RNASE T1	0.0004–0.0006	2
SUCCINYL-ALA-ALA-PRO-PHE 4-NITROANILIDE	0.451–1.247	2
SUCCINYL-ALA-LYS-PRO-PHE-4-NITROANILIDE	0.585–0.788	2
ALA-GLY-PSI[CS-N]-PRO-PHE-4-NITROANILIDE	0.53	1
N-SUCCINYL-ALA-LEU-(CIS)-PRO-PHE-4-NITROANILIDE	0.059	1
SUCCINYL-ALA-GLU-PRO-PHE-7-AMIDO-4-METHYLCOUMARI	0.12	1
TRYWNAKMK-(CIS)-PFIFGA	2	1
SUCCINYL-ALA-ALA-(CIS)-PRO-LYS-4-METHYLCOUMARIN-	—	0
SUCCINYL-ALA-ALA-(CIS)-PRO-PHE 4-METHYLCOUMARIN	—	0

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (63 total): modified residue 19, compositionally biased region 14, strand 12, turn 6, helix 3, cross-link 2, splice variant 2, sequence variant 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2WFI	X-RAY DIFFRACTION	0.75
2WFJ	X-RAY DIFFRACTION	0.75
2GW2	X-RAY DIFFRACTION	1.8
5YZG	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13427-F1	56.64	0.20

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 (21): 254, 256, 257, 259, 290, 315, 356, 358, 386, 397, 413, 415, 687, 690, 696, 744, 745, 748, 753, 392 …

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses

MSigDB gene sets: 162 (showing top): GCM_MAP4K4, GCM_GSPT1, CMYB_01, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, CREBP1_Q2, PUJANA_CHEK2_PCC_NETWORK, CREB_Q4, E2F1DP1_01, GOBP_PROTEIN_MATURATION, E2F1DP2_01, BLALOCK_ALZHEIMERS_DISEASE_UP, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, GOBP_PROTEIN_FOLDING

GO Biological Process (3): protein folding (GO:0006457), RNA splicing (GO:0008380), protein peptidyl-prolyl isomerization (GO:0000413)

GO Molecular Function (5): RNA binding (GO:0003723), peptidyl-prolyl cis-trans isomerase activity (GO:0003755), cyclosporin A binding (GO:0016018), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear matrix (GO:0016363), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
mRNA Splicing	1
SARS-CoV-1-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
binding	2
nuclear lumen	2
cellular process	1
protein maturation	1
RNA processing	1
peptidyl-proline modification	1
nucleic acid binding	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

5032 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPIG	CYP3A4	P05184	974
PPIG	CYP2B6	P20813	964
PPIG	CYP2D6	P10635	961
PPIG	CYP2C8	P10632	957
PPIG	CYP2C19	P33259	957
PPIG	CYP2C9	P11712	956
PPIG	CYP1A2	P05177	951
PPIG	CYP2A6	P00190	949
PPIG	POR	P16435	943
PPIG	CYP2E1	P05181	939
PPIG	CYP1A1	P04798	934
PPIG	CYP2J2	P51589	927
PPIG	CYP3A5	P20815	926
PPIG	SH2D3A	Q9BRG2	926
PPIG	SLC35A2	P78381	923

IntAct

158 interactions, top by confidence:

A	B	Type	Score
SARNP	DDX39A	psi-mi:“MI:0914”(association)	0.740
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
RBM39	PPIG	psi-mi:“MI:0915”(physical association)	0.670
PPIG	SMN1	psi-mi:“MI:0915”(physical association)	0.670
SMN1	PPIG	psi-mi:“MI:0915”(physical association)	0.670
PPIG	RBM39	psi-mi:“MI:0915”(physical association)	0.670
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
SNRPA1	U2SURP	psi-mi:“MI:0914”(association)	0.640
SARNP	ZC3H11A	psi-mi:“MI:0914”(association)	0.610
YWHAG	PPIG	psi-mi:“MI:0915”(physical association)	0.590
DAB1	PPIG	psi-mi:“MI:0915”(physical association)	0.560
LGALS3	PPIG	psi-mi:“MI:0915”(physical association)	0.560
TFCP2	PPIG	psi-mi:“MI:0915”(physical association)	0.560
PPIG	LGALS3	psi-mi:“MI:0915”(physical association)	0.560
PPIG	BEND7	psi-mi:“MI:0915”(physical association)	0.560
KCTD6	PPIG	psi-mi:“MI:0915”(physical association)	0.560
PPIG	CEP70	psi-mi:“MI:0915”(physical association)	0.560
FHL3	PPIG	psi-mi:“MI:0915”(physical association)	0.560
PPCDC	PPIG	psi-mi:“MI:0915”(physical association)	0.560
THAP1	PPIG	psi-mi:“MI:0915”(physical association)	0.560
PPIG	DACH1	psi-mi:“MI:0915”(physical association)	0.560
PNMA2	PPIG	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (181): PPIG (Two-hybrid), PPIG (Two-hybrid), PPIG (Two-hybrid), PPIG (Two-hybrid), PPIG (Two-hybrid), PPIG (Two-hybrid), RBM39 (Two-hybrid), PNMA2 (Two-hybrid), THAP1 (Two-hybrid), PPCDC (Two-hybrid), CEP70 (Two-hybrid), KCTD6 (Two-hybrid), BEND7 (Two-hybrid), PPIG (Affinity Capture-MS), PPIG (Affinity Capture-MS)

ESM2 similar proteins: A0A1S3XQD6, A0A1S4AX27, A1A5I1, A2AR02, A6QLS2, B0BN49, G2TRQ9, O14256, O55035, P30189, P30414, P41512, Q04750, Q07050, Q13427, Q27450, Q28EE8, Q3KPW4, Q4V9W2, Q505I5, Q59LQ5, Q5BKY9, Q5R8J6, Q5RJP9, Q5VTL8, Q5XHJ5, Q5ZLM8, Q6AXY7, Q6BNE1, Q6NQD9, Q6NWI1, Q6ZUT1, Q751P0, Q7L4I2, Q7YR26, Q80SY5, Q8GWY0, Q8N9E0, Q8N9Q2, Q8R0F5

Diamond homologs: A0A0R0H9T5, A2AR02, A8X8D0, D4AY02, O49886, O55035, O74729, O93826, O94273, P0C1H7, P0C1H9, P0C1I1, P0C1I2, P0C1I3, P0C1I7, P0C1I8, P0C1I9, P0CP82, P0CP83, P14088, P14832, P18253, P21568, P21569, P23284, P24367, P24368, P24369, P24525, P25007, P25719, P26882, P30414, P30415, P34790, P34791, P34887, P35627, P52009, P52010

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 143 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of Mature Transcript to Cytoplasm	12	49.1×	2e-16
RNA Polymerase II Transcription Termination	15	35.4×	4e-18
mRNA 3’-end processing	15	31.8×	2e-17
mRNA Splicing	21	24.8×	5e-22
Processing of Capped Intron-Containing Pre-mRNA	26	23.0×	1e-26
Transport of Mature mRNA derived from an Intron-Containing Transcript	14	22.9×	4e-14
mRNA Polyadenylation	20	18.9×	1e-18
mRNA Splicing - Major Pathway	30	17.6×	3e-27

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	7	43.2×	3e-08
regulation of mRNA splicing, via spliceosome	6	42.9×	4e-07
mRNA splice site recognition	5	32.4×	4e-05
RNA splicing, via transesterification reactions	5	25.2×	1e-04
U2-type prespliceosome assembly	5	25.2×	1e-04
regulation of alternative mRNA splicing, via spliceosome	9	17.7×	3e-07
RNA splicing	22	15.7×	2e-17
mRNA splicing, via spliceosome	19	14.0×	3e-14

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2114 predictions. Top by Δscore:

Variant	Effect	Δscore
2:169584487:GCAG:G	donor_gain	1.0000
2:169584491:G:GG	donor_gain	1.0000
2:169584491:GTAA:G	donor_loss	1.0000
2:169604024:A:AG	acceptor_gain	1.0000
2:169604025:G:GG	acceptor_gain	1.0000
2:169604100:CTGG:C	donor_loss	1.0000
2:169604101:TGGTA:T	donor_loss	1.0000
2:169604103:GT:G	donor_loss	1.0000
2:169604104:T:G	donor_loss	1.0000
2:169606034:TATA:T	acceptor_loss	1.0000
2:169606035:ATAG:A	acceptor_gain	1.0000
2:169606036:T:G	acceptor_gain	1.0000
2:169606036:TA:T	acceptor_loss	1.0000
2:169606037:A:AG	acceptor_gain	1.0000
2:169606038:G:GC	acceptor_gain	1.0000
2:169606038:GGT:G	acceptor_gain	1.0000
2:169606038:GGTGA:G	acceptor_gain	1.0000
2:169606145:AGGTG:A	donor_loss	1.0000
2:169606147:G:GG	donor_gain	1.0000
2:169606147:GT:G	donor_loss	1.0000
2:169606148:T:A	donor_loss	1.0000
2:169607100:TTAGG:T	acceptor_loss	1.0000
2:169607101:TA:T	acceptor_loss	1.0000
2:169607102:A:AG	acceptor_gain	1.0000
2:169607102:AG:A	acceptor_gain	1.0000
2:169607103:G:GA	acceptor_gain	1.0000
2:169607103:G:GT	acceptor_loss	1.0000
2:169607103:GG:G	acceptor_gain	1.0000
2:169607103:GGA:G	acceptor_gain	1.0000
2:169607103:GGAA:G	acceptor_gain	1.0000

AlphaMissense

5063 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:169604069:T:C	C10R	1.000
2:169604070:G:A	C10Y	1.000
2:169604071:T:G	C10W	1.000
2:169604072:T:C	F11L	1.000
2:169604074:T:A	F11L	1.000
2:169604074:T:G	F11L	1.000
2:169604194:A:C	R23S	1.000
2:169604194:A:T	R23S	1.000
2:169604196:T:A	V24D	1.000
2:169604208:T:C	L28S	1.000
2:169604224:C:G	C33W	1.000
2:169604235:G:A	C37Y	1.000
2:169604236:C:G	C37W	1.000
2:169604240:A:C	N39H	1.000
2:169604240:A:G	N39D	1.000
2:169604242:C:A	N39K	1.000
2:169604242:C:G	N39K	1.000
2:169604243:T:C	F40L	1.000
2:169604244:T:C	F40S	1.000
2:169604244:T:G	F40C	1.000
2:169604245:T:A	F40L	1.000
2:169604245:T:G	F40L	1.000
2:169604246:C:A	R41S	1.000
2:169604247:G:C	R41P	1.000
2:169604253:T:A	L43H	1.000
2:169604253:T:C	L43P	1.000
2:169604255:T:C	C44R	1.000
2:169604256:G:A	C44Y	1.000
2:169604256:G:T	C44F	1.000
2:169604257:T:G	C44W	1.000

dbSNP variants (sampled 300 via entrez): RS1000039045 (2:169640782 A>G), RS1000052548 (2:169630070 T>A,G), RS1000092050 (2:169608016 C>T), RS1000206227 (2:169608317 C>A,T), RS1000278307 (2:169600417 C>A), RS1000331117 (2:169600687 GAA>G,GA,GAAA), RS1000391888 (2:169602734 A>C,G), RS1000404371 (2:169596858 C>G,T), RS1000439230 (2:169635724 G>A), RS1000490046 (2:169595231 A>G), RS1000490538 (2:169634541 A>G), RS1000504618 (2:169628871 G>A), RS1000578987 (2:169605834 G>A,T), RS1000615756 (2:169601620 G>A), RS1000652883 (2:169591464 A>G)

Disease associations

OMIM: gene MIM:606093 | 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: yes

ChEMBL targets (1): CHEMBL3707467 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

Binding affinities (BindingDB)

10 measured of 10 human assays (10 total across all organisms); most potent 10 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[(4-aminophenyl)methyl]-3-[2-[2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	IC50	650 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
1-[(4-aminophenyl)methyl]-3-[4-methylsulfanyl-1-[2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-1-oxobutan-2-yl]urea	IC50	660 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
1-[(4-aminophenyl)methyl]-3-[2-[2-(2-bromophenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	IC50	760 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
1-[(4-aminophenyl)methyl]-3-[1-[2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-1-oxopropan-2-yl]urea	IC50	1100 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
1-[(4-aminophenyl)methyl]-3-[2-[2-(2-methoxyphenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	IC50	1200 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
1-[(4-aminophenyl)methyl]-3-[2-(2-naphthalen-1-ylpyrrolidin-1-yl)-2-oxoethyl]urea	IC50	1400 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
1-[(4-aminophenyl)methyl]-3-[4-methyl-1-[2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-1-oxopentan-2-yl]urea	IC50	3000 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
2-[(4-aminophenyl)methylcarbamoylamino]-N-ethyl-N-phenylmethoxyacetamide	IC50	4800 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
ethyl 2-[(4-aminophenyl)methylcarbamoylamino]acetate	IC50	6100 nM	US-8901295: Inhibitors of cyclophilins and uses thereof
1-[(4-aminophenyl)methyl]-3-[2-[2-(2-chlorophenyl)pyrrolidin-1-yl]-2-oxoethyl]urea	IC50	6200 nM	US-8901295: Inhibitors of cyclophilins and uses thereof

ChEMBL bioactivities

11 potent at pChembl≥5 of 12 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	IC50	10	nM	MOLIBRESIB
7.96	Kd	11	nM	MOLIBRESIB
6.43	IC50	370	nM	CHEMBL3647433
6.25	IC50	560	nM	CHEMBL3647432
6.10	IC50	790	nM	CHEMBL3647436
5.82	IC50	1500	nM	CHEMBL3647431
5.55	IC50	2800	nM	CHEMBL3647430
5.51	IC50	3100	nM	CHEMBL3647435
5.48	IC50	3300	nM	CHEMBL3647434
5.47	IC50	3400	nM	CHEMBL3639462
5.05	IC50	9000	nM	CHEMBL3647438

PubChem BioAssay actives

2 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178545: Inhibition of PPIG (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	4
perfluorooctane sulfonic acid	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
N(6)-(delta(2)-isopentenyl)adenine	increases expression	1
testosterone enanthate	affects expression	1
chloroacetaldehyde	decreases expression	1
sodium arsenate	decreases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
cotylenin A	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	decreases methylation	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Cidofovir	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Asbestos	affects expression	1
Aspirin	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Clodronic Acid	decreases expression	1
Dietary Carbohydrates	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3707943	Binding	Enzymatic Assay: Cyclophilin PPlase activity was measured at 20 C. by using the standard chymotrypsin coupled assay (Kofron J L, Kuzmic P, Kishore V, Colon-Bonilla E, Rich D H. Determination of kinetic constants for peptidyl prolyl cis-tran	Inhibitors of cyclophilins and uses thereof

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2HD	HAP1 PPIG (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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