PPIAL4C

Summary

PPIAL4C (peptidylprolyl isomerase A like 4C, HGNC:33995) is a protein-coding gene on chromosome 1q21.2, encoding Peptidyl-prolyl cis-trans isomerase A-like 4C (A0A0B4J2A2). 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. Located in extracellular exosome.

Source: NCBI Gene 653598 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001135789

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33995
Approved symbol	PPIAL4C
Name	peptidylprolyl isomerase A like 4C
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000288867
Ensembl biotype	protein_coding
Entrez	653598

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000585245

RefSeq mRNA: 1 — MANE Select: NM_001135789 NM_001135789

CCDS: CCDS72898

Canonical transcript exons

ENST00000585245 — 1 exons

Exon	Start	End
ENSE00001710992	149583848	149584607

Expression profiles

Top tissues by expression

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting PPIAL4C, 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-1252-5P	100.00	69.80	2774
HSA-MIR-1184	99.99	68.19	1458
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

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), PPIAL4E (ENSG00000271567), PPIAL4F (ENSG00000279782), PPIAL4D (ENSG00000289549)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase A-like 4C — A0A0B4J2A2 (reviewed: A0A0B4J2A2)

All UniProt accessions (1): A0A0B4J2A2

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_001129261* (*=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-A0A0B4J2A2-F1	96.63	0.98

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

1836 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPIAL4C	NBPF12	Q5TAG4	988
PPIAL4C	PRSS38	A1L453	513
PPIAL4C	NBPF20	P0DPF2	435
PPIAL4C	SCCPDH	Q8NBX0	355
PPIAL4C	ZDHHC1	Q8WTX9	322
PPIAL4C	TSPAN31	Q12999	321
PPIAL4C	DAPL1	A0PJW8	290
PPIAL4C	ATP4B	P51164	271
PPIAL4C	RASA4	O43374	250
PPIAL4C	CRAT	P43155	245
PPIAL4C	AKR1D1	P51857	235
PPIAL4C	ACAT1	P24752	226
PPIAL4C	FOXK2	Q01167	226
PPIAL4C	HS6ST1	O60243	222
PPIAL4C	TPCN2	Q8NHX9	220
PPIAL4C	CAPZA2	P47755	220

IntAct

7 interactions, top by confidence:

A	B	Type	Score
PPIAL4C	H1-1	psi-mi:“MI:0915”(physical association)	0.400
PPIAL4C	HMGN2	psi-mi:“MI:0915”(physical association)	0.400
SERPINB9	PPIAL4C	psi-mi:“MI:0914”(association)	0.350
MED17	PPIAL4C	psi-mi:“MI:0914”(association)	0.350
LAGE3	PPIAL4C	psi-mi:“MI:0914”(association)	0.350
CD151	PPIAL4C	psi-mi:“MI:0914”(association)	0.350

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

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

66 predictions. Top by Δscore:

Variant	Effect	Δscore
1:149583852:A:G	donor_gain	0.9900
1:149583865:G:GA	donor_gain	0.8100
1:149583937:G:A	donor_gain	0.7500
1:149583924:A:AG	donor_gain	0.6900
1:149583866:T:TA	donor_gain	0.6400
1:149584267:G:A	donor_gain	0.5700
1:149584252:A:AC	donor_gain	0.5600
1:149584252:AGT:A	donor_gain	0.5600
1:149584258:C:CT	donor_gain	0.5400
1:149583870:A:AG	donor_gain	0.5300
1:149584285:G:A	donor_gain	0.5300
1:149583864:GC:G	donor_gain	0.5200
1:149583907:G:GT	donor_gain	0.5200
1:149583884:CAGGG:C	donor_gain	0.4700
1:149583887:G:GG	donor_gain	0.4400
1:149583888:A:AG	donor_gain	0.4400
1:149584257:C:CT	donor_gain	0.4400
1:149584305:T:C	donor_gain	0.4200
1:149583873:G:GG	donor_gain	0.4100
1:149583874:A:AG	donor_gain	0.4100
1:149583888:A:AC	donor_gain	0.4100
1:149583874:A:C	donor_gain	0.3500
1:149584251:G:C	donor_gain	0.3500
1:149583875:C:CC	donor_gain	0.3300
1:149583876:A:AC	donor_gain	0.3300
1:149583926:TG:T	donor_gain	0.3300
1:149584293:TTC:T	donor_gain	0.3300
1:149584314:T:TA	donor_gain	0.3300
1:149583883:AGGG:A	donor_gain	0.3200
1:149584260:A:T	donor_gain	0.3200

AlphaMissense

1103 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:149583916:T:C	F7L	0.846
1:149583918:T:A	F7L	0.846
1:149583918:T:G	F7L	0.846
1:149584282:T:C	F129L	0.846
1:149584284:T:A	F129L	0.846
1:149584284:T:G	F129L	0.846
1:149584231:T:C	F112L	0.839
1:149584233:T:A	F112L	0.839
1:149584233:T:G	F112L	0.839
1:149584075:T:C	F60L	0.837
1:149584077:T:A	F60L	0.837
1:149584077:T:G	F60L	0.837
1:149584144:T:C	F83L	0.808
1:149584146:T:A	F83L	0.808
1:149584146:T:G	F83L	0.808
1:149584054:T:C	F53L	0.788
1:149584056:T:A	F53L	0.788
1:149584056:T:G	F53L	0.788
1:149584003:T:C	F36L	0.777
1:149584005:T:A	F36L	0.777
1:149584005:T:G	F36L	0.777
1:149584096:T:C	F67L	0.733
1:149584098:C:A	F67L	0.733
1:149584098:C:G	F67L	0.733
1:149583970:T:C	F25L	0.730
1:149583972:T:A	F25L	0.730
1:149583972:T:G	F25L	0.730
1:149584234:T:C	F113L	0.699
1:149584236:C:A	F113L	0.699
1:149584236:C:G	F113L	0.699

dbSNP variants (sampled 300 via entrez): RS1156626098 (1:149584222 G>A,C,T), RS1157720329 (1:149582119 G>A,C), RS1157783119 (1:149583885 T>A), RS1158355395 (1:149582767 T>C), RS1158872557 (1:149584640 G>C), RS1159060167 (1:149582189 T>G), RS1159190569 (1:149582827 T>G), RS1159263482 (1:149583498 G>GA), RS1159792147 (1:149582136 G>A), RS1160245871 (1:149583893 C>T), RS1160264286 (1:149584785 C>A,T), RS1160848563 (1:149582481 C>A,T), RS1161470390 (1:149583585 AAG>A), RS1161652447 (1:149581878 C>G,T), RS1162417373 (1:149584268 G>A)

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

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.