PPIL6

Summary

PPIL6 (peptidylprolyl isomerase like 6, HGNC:21557) is a protein-coding gene on chromosome 6q21, encoding Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 (Q8IXY8). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity.

Predicted to enable RNA polymerase II CTD heptapeptide repeat P3 isomerase activity and RNA polymerase II CTD heptapeptide repeat P6 isomerase activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in cytoplasm.

Source: NCBI Gene 285755 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 68 total
• MANE Select transcript: NM_173672

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21557
Approved symbol	PPIL6
Name	peptidylprolyl isomerase like 6
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	bA425D10.6, MGC41939, dJ919F19.1, RSPH12
Ensembl gene	ENSG00000185250
Ensembl biotype	protein_coding
Entrez	285755

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000417394, ENST00000424445, ENST00000440797, ENST00000447468, ENST00000518648, ENST00000520723, ENST00000521072, ENST00000524031, ENST00000897716, ENST00000897717, ENST00000897718, ENST00000961131, ENST00000961132, ENST00000961133

RefSeq mRNA: 4 — MANE Select: NM_173672 NM_001111298, NM_001286360, NM_001286361, NM_173672

CCDS: CCDS47466, CCDS5074, CCDS69169

Canonical transcript exons

ENST00000521072 — 8 exons

Exon	Start	End
ENSE00001296630	109431157	109431345
ENSE00001306599	109436104	109436199
ENSE00003490339	109426847	109426994
ENSE00003558647	109419187	109419243
ENSE00003573693	109427094	109427156
ENSE00003655910	109400035	109400170
ENSE00003701651	109390215	109392937
ENSE00003896640	109440456	109440628

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 93.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.7093 / max 52.7769, expressed in 1038 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74996	2.5623	1013
74997	0.0805	32
74998	0.0666	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	93.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.67	gold quality
sperm	CL:0000019	88.15	silver quality
right testis	UBERON:0004534	88.02	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.02	silver quality
left testis	UBERON:0004533	87.83	gold quality
calcaneal tendon	UBERON:0003701	86.39	gold quality
testis	UBERON:0000473	85.18	gold quality
cortical plate	UBERON:0005343	84.40	gold quality
ventricular zone	UBERON:0003053	84.32	gold quality
bronchial epithelial cell	CL:0002328	83.17	gold quality
epithelium of bronchus	UBERON:0002031	82.89	gold quality
bronchus	UBERON:0002185	81.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.50	gold quality
epithelium of nasopharynx	UBERON:0001951	78.79	silver quality
islet of Langerhans	UBERON:0000006	78.37	gold quality
ganglionic eminence	UBERON:0004023	77.18	gold quality
fallopian tube	UBERON:0003889	77.01	gold quality
left lobe of thyroid gland	UBERON:0001120	76.98	gold quality
thyroid gland	UBERON:0002046	76.59	gold quality
nucleus accumbens	UBERON:0001882	75.33	gold quality
caudate nucleus	UBERON:0001873	75.26	gold quality
right lobe of thyroid gland	UBERON:0001119	75.25	gold quality
tendon	UBERON:0000043	74.65	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.93	gold quality
prefrontal cortex	UBERON:0000451	73.68	gold quality
left ovary	UBERON:0002119	73.68	gold quality
Brodmann (1909) area 9	UBERON:0013540	73.49	gold quality
pancreas	UBERON:0001264	73.27	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	26.19
E-ANND-3	yes	8.49
E-MTAB-9388	yes	7.40
E-ENAD-17	no	88.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting PPIL6, 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-4795-3P	100.00	74.62	4024
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppil6	ENSDARG00000042157
mus_musculus	Ppil6	ENSMUSG00000078451
rattus_norvegicus	Ppil6	ENSRNOG00000043186
drosophila_melanogaster	Cyp40	FBGN0036020
caenorhabditis_elegans		WBGENE00000885

Paralogs (22): PPIE (ENSG00000084072), PPIL2 (ENSG00000100023), PPIF (ENSG00000108179), PPWD1 (ENSG00000113593), NKTR (ENSG00000114857), PPIL4 (ENSG00000131013), PPIL1 (ENSG00000137168), PPIG (ENSG00000138398), CWC27 (ENSG00000153015), PPIB (ENSG00000166794), PPIC (ENSG00000168938), PPID (ENSG00000171497), PPIH (ENSG00000171960), PPIA (ENSG00000196262), PPIAL4G (ENSG00000236334), PPIL3 (ENSG00000240344), PPIAL4A (ENSG00000263353), PPIAL4H (ENSG00000270339), PPIAL4E (ENSG00000271567), PPIAL4F (ENSG00000279782), PPIAL4C (ENSG00000288867), PPIAL4D (ENSG00000289549)

Protein

Protein identifiers

Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 — Q8IXY8 (reviewed: Q8IXY8)

Alternative names: Cyclophilin-like protein PPIL6, Rotamase PPIL6

All UniProt accessions (5): B4DEK6, Q8IXY8, H0Y7C3, H0YAQ8, H0YC62

UniProt curated annotations — full annotation on UniProt →

Function. Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity.

Similarity. Belongs to the cyclophilin-type PPIase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IXY8-1	1	yes
Q8IXY8-2	2
Q8IXY8-3	3

RefSeq proteins (4): NP_001104768, NP_001273289, NP_001273290, NP_775943* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002130	Cyclophilin-type_PPIase_dom	Domain
IPR029000	Cyclophilin-like_dom_sf	Homologous_superfamily

Pfam: PF00160

UniProt features (5 total): splice variant 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXY8-F1	92.39	0.86

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 65 (showing top): SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, MARIADASON_RESPONSE_TO_BUTYRATE_CURCUMIN_SULINDAC_TSA_8, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, GOMF_CIS_TRANS_ISOMERASE_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_ISOMERASE_ACTIVITY, LU_EZH2_TARGETS_UP, FIGUEROA_AML_METHYLATION_CLUSTER_6_UP, REACTOME_INFECTIOUS_DISEASE, FOXD2_TARGET_GENES, FOXJ2_TARGET_GENES, HAND1_TARGET_GENES, NFKBIA_TARGET_GENES, SNIP1_TARGET_GENES, ZIM3_TARGET_GENES

GO Biological Process (1): protein peptidyl-prolyl isomerization (GO:0000413)

GO Molecular Function (3): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (1): cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptidyl-proline modification	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1634 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPIL6	SYF2	O95926	532
PPIL6	ZBTB24	O43167	474
PPIL6	RSPH3	Q86UC2	464
PPIL6	ATAD5	Q96QE3	449
PPIL6	RSPH14	Q9UHP6	430
PPIL6	SLC67A2	Q8NBP5	400
PPIL6	MTRES1	Q9P0P8	377
PPIL6	PPIL4	Q8WUA2	369
PPIL6	CFAP300	Q9BRQ4	367
PPIL6	DNAJC27	Q9NZQ0	357
PPIL6	LSAMP	Q13449	341
PPIL6	RFC4	P35249	339
PPIL6	EYA4	O95677	339
PPIL6	RSPH9	Q9H1X1	330
PPIL6	CHURC1	Q8WUH1	330

IntAct

13 interactions, top by confidence:

A	B	Type	Score
SORBS3	PPIL6	psi-mi:“MI:0915”(physical association)	0.560
PPIL6	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
BAG4	PPIL6	psi-mi:“MI:0915”(physical association)	0.560
BIVM	PPIL6	psi-mi:“MI:0915”(physical association)	0.560
PPIL6	SORBS3	psi-mi:“MI:0915”(physical association)	0.000
PPIL6	BAG4	psi-mi:“MI:0915”(physical association)	0.000
PPIL6	APPBP2	psi-mi:“MI:0915”(physical association)	0.000
PPIL6	BIVM	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): PPIL6 (Affinity Capture-MS), PPIL6 (Synthetic Lethality), PPIL6 (Two-hybrid), PPIL6 (Two-hybrid), PPIL6 (Two-hybrid), PPIL6 (Two-hybrid), PPIL6 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0AVT1, A0JMM9, A2RVS4, A3KMX8, A3KNL6, A6H630, A8MRP2, D2TN58, O74834, P0AE48, P0AE49, P0AE50, P0AE51, P35875, P38074, P41888, P54121, P87305, Q16P90, Q32LH7, Q4H4F0, Q4R526, Q58EM4, Q5SPB6, Q66I06, Q66KX0, Q6AXB1, Q6DJA3, Q6INN8, Q7L1T6, Q7TS68, Q84QC1, Q8GY54, Q8IU29, Q8IXY8, Q8RX87, Q8TEA1, Q9C5X8, Q9FIX1, Q9FIX2

Diamond homologs: A0A0R0H9T5, A2AR02, A8X8D0, B3A0R0, D4AY02, H2QII6, O43447, O49605, O49886, O55035, O93826, O94273, P0C1H7, P0C1I1, P0C1I3, P0C1I7, P0C1I8, P0C1I9, P0CP78, P0CP79, P14088, P14832, P18253, P21568, P21569, P22011, P23285, P24525, P25007, P25719, P26882, P30404, P30412, P30414, P30415, P34790, P35176, P35627, P45877, P48820

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1672 predictions. Top by Δscore:

Variant	Effect	Δscore
6:109400168:CAT:C	acceptor_gain	1.0000
6:109400170:TC:T	acceptor_loss	1.0000
6:109400171:C:A	acceptor_loss	1.0000
6:109400171:C:CC	acceptor_gain	1.0000
6:109400172:T:G	acceptor_loss	1.0000
6:109419182:CATA:C	donor_loss	1.0000
6:109419183:ATAC:A	donor_loss	1.0000
6:109419184:TA:T	donor_loss	1.0000
6:109419185:ACC:A	donor_loss	1.0000
6:109419186:C:CA	donor_loss	1.0000
6:109429731:C:A	donor_gain	1.0000
6:109431179:G:C	donor_gain	1.0000
6:109436102:AC:A	donor_gain	1.0000
6:109436103:CC:C	donor_gain	1.0000
6:109436208:C:CT	acceptor_gain	1.0000
6:109441168:GCTG:G	donor_gain	1.0000
6:109400029:ACAT:A	donor_loss	0.9900
6:109400030:CAT:C	donor_loss	0.9900
6:109400031:ATA:A	donor_loss	0.9900
6:109400032:TA:T	donor_loss	0.9900
6:109400033:A:AC	donor_gain	0.9900
6:109400033:A:AG	donor_loss	0.9900
6:109400033:AC:A	donor_gain	0.9900
6:109400034:C:CC	donor_gain	0.9900
6:109400034:C:CG	donor_loss	0.9900
6:109400034:CC:C	donor_gain	0.9900
6:109400166:TTCAT:T	acceptor_gain	0.9900
6:109400167:TCAT:T	acceptor_gain	0.9900
6:109400168:CATC:C	acceptor_gain	0.9900
6:109400169:AT:A	acceptor_gain	0.9900

AlphaMissense

2054 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:109426879:C:G	R200P	0.994
6:109440503:C:A	G30W	0.988
6:109400035:C:T	G275E	0.987
6:109436133:A:G	W68R	0.987
6:109436133:A:T	W68R	0.987
6:109400036:C:A	G275W	0.986
6:109400131:A:T	L243H	0.986
6:109400037:A:C	F274L	0.985
6:109400037:A:T	F274L	0.985
6:109400039:A:G	F274L	0.985
6:109426957:A:G	F174S	0.984
6:109431263:A:G	L105P	0.984
6:109436195:A:G	L47P	0.984
6:109400041:G:T	A273D	0.983
6:109400088:G:C	F257L	0.983
6:109400088:G:T	F257L	0.983
6:109400090:A:G	F257L	0.983
6:109426862:A:G	W206R	0.983
6:109426862:A:T	W206R	0.983
6:109426956:A:C	F174L	0.983
6:109426956:A:T	F174L	0.983
6:109426958:A:G	F174L	0.983
6:109440502:C:T	G30E	0.983
6:109400089:A:G	F257S	0.982
6:109440460:G:T	A44D	0.982
6:109426959:A:C	N173K	0.981
6:109426959:A:T	N173K	0.981
6:109440461:C:G	A44P	0.981
6:109440503:C:G	G30R	0.980
6:109440503:C:T	G30R	0.980

dbSNP variants (sampled 300 via entrez): RS1000056939 (6:109437362 G>A,T), RS1000218907 (6:109398829 A>G), RS1000232437 (6:109419387 C>G,T), RS1000299142 (6:109435703 T>A), RS1000315803 (6:109433070 T>C), RS1000415180 (6:109400868 T>G), RS1000559993 (6:109420893 T>A), RS1000595802 (6:109427559 G>C,T), RS1000652146 (6:109434570 C>T), RS1000664085 (6:109425767 A>G), RS1000727337 (6:109422158 G>T), RS1000786246 (6:109407249 T>C), RS1000901178 (6:109434573 T>C), RS1000923525 (6:109406936 A>G), RS1000982062 (6:109440564 G>A,C,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

7 associations (top):

Study	Trait	p-value
GCST000175_27	Height	4.000000e-06
GCST002647_58	Height	2.000000e-17
GCST90002385_566	High light scatter reticulocyte count	5.000000e-18
GCST90002386_108	High light scatter reticulocyte percentage of red cells	5.000000e-11
GCST90002388_2	Lymphocyte count	5.000000e-10
GCST90002389_333	Lymphocyte percentage of white cells	6.000000e-13
GCST90002399_304	Neutrophil percentage of white cells	2.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation, affects cotreatment	3
bisphenol A	decreases expression, decreases methylation, increases methylation	2
Air Pollutants	increases abundance, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tretinoin	decreases expression	2
Particulate Matter	increases abundance, increases expression	2
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
MT19c compound	increases expression	1
Rosiglitazone	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	increases expression	1
Niclosamide	increases expression	1
Phenobarbital	increases expression	1
Rotenone	increases expression	1
Dihydrotestosterone	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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