PPIAL4E

Summary

PPIAL4E (peptidylprolyl isomerase A like 4E, HGNC:33997) is a protein-coding gene on chromosome 1q21.1, encoding Peptidyl-prolyl cis-trans isomerase A-like 4E (A0A075B759). PPIases accelerate the folding of proteins.

Predicted to enable cyclosporin A binding activity and peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in protein folding. Predicted to be active in cytoplasm.

Source: NCBI Gene 730262 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_001144032

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33997
Approved symbol	PPIAL4E
Name	peptidylprolyl isomerase A like 4E
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000271567
Ensembl biotype	protein_coding
OMIM	608608
Entrez	730262

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000581164

RefSeq mRNA: 1 — MANE Select: NM_001144032 NM_001144032

CCDS: CCDS76201

Canonical transcript exons

ENST00000581164 — 1 exons

Exon	Start	End
ENSE00003927151	144372875	144373634

Expression profiles

Bgee: expression breadth ubiquitous, 103 present calls, max score 65.47.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	65.47	gold quality
apex of heart	UBERON:0002098	54.89	gold quality
cerebellar hemisphere	UBERON:0002245	54.12	gold quality
cerebellar cortex	UBERON:0002129	53.66	gold quality
cerebellum	UBERON:0002037	53.32	gold quality
lower esophagus mucosa	UBERON:0035834	52.34	gold quality
right hemisphere of cerebellum	UBERON:0014890	52.21	gold quality
stromal cell of endometrium	CL:0002255	49.49	gold quality
calcaneal tendon	UBERON:0003701	49.06	gold quality
spleen	UBERON:0002106	48.63	gold quality
corpus callosum	UBERON:0002336	46.52	silver quality
blood	UBERON:0000178	44.84	gold quality
amygdala	UBERON:0001876	44.52	gold quality
temporal lobe	UBERON:0001871	44.31	gold quality
ectocervix	UBERON:0012249	44.17	gold quality
putamen	UBERON:0001874	42.73	gold quality
leukocyte	CL:0000738	42.71	gold quality
endocervix	UBERON:0000458	42.40	gold quality
uterine cervix	UBERON:0000002	42.18	gold quality
anterior cingulate cortex	UBERON:0009835	42.08	gold quality
bone marrow	UBERON:0002371	42.03	silver quality
brain	UBERON:0000955	41.50	gold quality
nucleus accumbens	UBERON:0001882	41.41	gold quality
hypothalamus	UBERON:0001898	41.39	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	41.25	gold quality
lymph node	UBERON:0000029	40.89	gold quality
caudate nucleus	UBERON:0001873	40.88	gold quality
right frontal lobe	UBERON:0002810	40.70	gold quality
bone marrow cell	CL:0002092	40.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	40.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting PPIAL4E, 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-4802-3P	99.72	70.13	1273
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-3622B-5P	94.62	64.58	835
HSA-MIR-6750-5P	93.94	66.68	797
HSA-MIR-6822-5P	93.94	66.34	812

Literature-anchored findings (GeneRIF, showing 1)

• Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma. (PMID:22320715)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppifa	ENSDARG00000007409
danio_rerio	ppiaa	ENSDARG00000009212
danio_rerio	ppiab	ENSDARG00000103994
drosophila_melanogaster	Cyp40	FBGN0036020
drosophila_melanogaster	Moca-cyp	FBGN0039581
caenorhabditis_elegans		WBGENE00000877
caenorhabditis_elegans		WBGENE00000878
caenorhabditis_elegans		WBGENE00000879
caenorhabditis_elegans		WBGENE00000883
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), PPIL6 (ENSG00000185250), PPIA (ENSG00000196262), PPIAL4G (ENSG00000236334), PPIL3 (ENSG00000240344), PPIAL4A (ENSG00000263353), PPIAL4H (ENSG00000270339), PPIAL4F (ENSG00000279782), PPIAL4C (ENSG00000288867), PPIAL4D (ENSG00000289549)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase A-like 4E — A0A075B759 (reviewed: A0A075B759)

All UniProt accessions (1): A0A075B759

UniProt curated annotations — full annotation on UniProt →

Function. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.

Subcellular location. Cytoplasm.

Miscellaneous. It is one of six related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 1.

Similarity. Belongs to the cyclophilin-type PPIase family. PPIase A subfamily.

RefSeq proteins (1): NP_001137504* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002130	Cyclophilin-type_PPIase_dom	Domain
IPR020892	Cyclophilin-type_PPIase_CS	Conserved_site
IPR024936	Cyclophilin-type_PPIase	Family
IPR029000	Cyclophilin-like_dom_sf	Homologous_superfamily

Pfam: PF00160

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-A0A075B759-F1	96.74	0.99

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 11 (showing top): GOBP_PROTEIN_MATURATION, GOBP_PROTEIN_FOLDING, chr1q21, GOMF_CIS_TRANS_ISOMERASE_ACTIVITY, GOMF_AMIDE_BINDING, GOMF_ISOMERASE_ACTIVITY, GOMF_CYCLOSPORIN_A_BINDING, MIR548V, MIR6750_5P, MIR6822_5P, MIR3622B_5P

GO Biological Process (2): protein folding (GO:0006457), protein peptidyl-prolyl isomerization (GO:0000413)

GO Molecular Function (3): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), cyclosporin A binding (GO:0016018), isomerase activity (GO:0016853)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
protein maturation	1
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

1854 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPIAL4E	NBPF12	Q5TAG4	989
PPIAL4E	GOLGA8S	H3BPF8	647
PPIAL4E	C1orf105	O95561	515
PPIAL4E	PRSS38	A1L453	506
PPIAL4E	NBPF11	Q86T75	403
PPIAL4E	NBPF14	Q5TI25	402
PPIAL4E	NBPF15	Q8N660	378
PPIAL4E	OPRPN	P85047	326
PPIAL4E	ACP6	Q9NPH0	313
PPIAL4E	TSPAN31	Q12999	305
PPIAL4E	TCF25	Q9BQ70	302
PPIAL4E	LSG1	Q9H089	294
PPIAL4E	EPHX3	Q9H6B9	279
PPIAL4E	FMO5	P49326	278
PPIAL4E	NOTCH2NLB	P0DPK3	274

IntAct

0 interactions, top by confidence:

BioGRID (8): PPIAL4E (Affinity Capture-MS), PNN (Proximity Label-MS), PPIAL4E (Negative Genetic), PPIAL4F (Negative Genetic), PPIAL4E (Negative Genetic), PPIAL4F (Negative Genetic), PPIAL4E (Negative Genetic), PPIAL4F (Affinity Capture-MS)

ESM2 similar proteins: A0A075B759, A0A075B767, A0A0B4J2A2, F5H284, O00060, O43447, O74729, O94273, P0C1I0, P0C1I3, P0C1I5, P0C1I8, P0CP82, P0CP83, P0DN26, P0DN37, P17742, P23285, P24525, P25719, P52010, P52018, P62940, P84343, Q0P5D0, Q0ZQK7, Q0ZQK8, Q0ZQL0, Q0ZQL1, Q26516, Q26551, Q26565, Q27774, Q2TZ33, Q38867, Q38900, Q42406, Q4IPH4, Q4P6X6, Q4WCM6

Diamond homologs: A0A075B759, A0A075B767, A0A0B4J2A2, A0A0R0H9T5, A4FV72, D4AY02, F5H284, H2QII6, O00060, O49886, O93826, P0C1H7, P0C1H8, P0C1I2, P0C1I7, P0C1I8, P0C1I9, P0CP78, P0CP79, P0DN26, P0DN37, P10111, P10255, P14088, P14832, P14851, P17742, P18253, P21568, P21569, P22011, P24367, P24525, P25007, P25719, P29117, P30404, P30405, P34790, P34791

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

255 predictions. Top by Δscore:

Variant	Effect	Δscore
1:144373361:TGAC:T	donor_gain	0.8100
1:144373449:G:GT	donor_gain	0.8100
1:144373407:GGTT:G	donor_gain	0.7900
1:144372914:T:G	donor_gain	0.7700
1:144373405:TTT:T	donor_gain	0.7600
1:144373406:GTT:G	donor_gain	0.7600
1:144373457:A:T	donor_gain	0.7400
1:144373359:ACAA:A	donor_gain	0.7300
1:144373360:GACA:G	donor_gain	0.7300
1:144373541:C:T	donor_gain	0.7000
1:144373546:G:T	donor_gain	0.6700
1:144373599:GCCCT:G	donor_gain	0.6700
1:144373390:G:GA	donor_gain	0.6600
1:144373430:C:G	donor_gain	0.6300
1:144373211:C:T	donor_gain	0.6000
1:144373255:TCCC:T	donor_gain	0.6000
1:144373329:A:G	donor_gain	0.6000
1:144373453:A:T	donor_gain	0.5900
1:144373227:C:CG	donor_gain	0.5800
1:144373229:GAC:G	donor_gain	0.5800
1:144373392:G:T	donor_gain	0.5800
1:144372909:T:G	donor_gain	0.5700
1:144373221:G:GA	donor_gain	0.5700
1:144372909:T:TG	donor_gain	0.5600
1:144373343:G:T	donor_gain	0.5600
1:144373471:GCTC:G	donor_gain	0.5600
1:144373391:T:TA	donor_gain	0.5500
1:144373433:T:TA	donor_gain	0.5500
1:144373419:G:GT	donor_gain	0.5400
1:144373193:C:T	donor_gain	0.5300

AlphaMissense

1103 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS10909771 (1:144372595 G>A,T), RS111298700 (1:144375237 C>T), RS1161876246 (1:144373757 CT>C), RS1161988260 (1:144373734 A>C), RS1173392422 (1:144373938 CT>C), RS1186736842 (1:144373981 C>A,G,T), RS1188057186 (1:144374032 C>T), RS1199805338 (1:144373812 G>T), RS1209627464 (1:144374098 A>G), RS1210436741 (1:144373945 C>T), RS1212293810 (1:144374147 G>A), RS1213132571 (1:144373844 A>G,T), RS1231309905 (1:144373591 T>A,C), RS1232545233 (1:144373788 G>A,T), RS1241414911 (1:144374022 T>C,G)

Disease associations

OMIM: gene MIM:608608 | 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: no

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

Clinical trials (associated diseases)

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