PPIAL4G

Summary

PPIAL4G (peptidylprolyl isomerase A like 4G, HGNC:33996) is a protein-coding gene on chromosome 1q21.2, encoding Peptidyl-prolyl cis-trans isomerase A-like 4G (P0DN37). 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 644591 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_001123068

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33996
Approved symbol	PPIAL4G
Name	peptidylprolyl isomerase A like 4G
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000236334
Ensembl biotype	protein_coding
Entrez	644591

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000419275

RefSeq mRNA: 1 — MANE Select: NM_001123068 NM_001123068

CCDS: CCDS41375

Canonical transcript exons

ENST00000419275 — 1 exons

Exon	Start	End
ENSE00003734399	148482548	148483302

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 85.07.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.07	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.56	gold quality
calcaneal tendon	UBERON:0003701	65.57	gold quality
corpus callosum	UBERON:0002336	64.34	gold quality
granulocyte	CL:0000094	62.89	gold quality
adrenal tissue	UBERON:0018303	61.57	gold quality
sural nerve	UBERON:0015488	60.27	gold quality
mucosa of stomach	UBERON:0001199	57.52	gold quality
primary visual cortex	UBERON:0002436	53.62	gold quality
endometrium	UBERON:0001295	53.39	gold quality
duodenum	UBERON:0002114	52.99	gold quality
right coronary artery	UBERON:0001625	52.90	gold quality
nucleus accumbens	UBERON:0001882	52.19	gold quality
right uterine tube	UBERON:0001302	52.16	gold quality
pituitary gland	UBERON:0000007	52.02	gold quality
right adrenal gland cortex	UBERON:0035827	51.32	gold quality
cerebellar hemisphere	UBERON:0002245	50.37	gold quality
cerebellar cortex	UBERON:0002129	50.30	gold quality
cerebellum	UBERON:0002037	50.01	gold quality
left adrenal gland cortex	UBERON:0035825	49.84	gold quality
adenohypophysis	UBERON:0002196	49.71	gold quality
hypothalamus	UBERON:0001898	49.66	gold quality
anterior cingulate cortex	UBERON:0009835	49.31	gold quality
prefrontal cortex	UBERON:0000451	49.26	gold quality
bone marrow	UBERON:0002371	49.25	gold quality
descending thoracic aorta	UBERON:0002345	49.11	gold quality
brain	UBERON:0000955	48.72	gold quality
left uterine tube	UBERON:0001303	48.44	gold quality
frontal cortex	UBERON:0001870	48.30	gold quality
right lung	UBERON:0002167	48.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting PPIAL4G, 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-205-3P	99.92	69.92	3165
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), PPIL3 (ENSG00000240344), PPIAL4A (ENSG00000263353), PPIAL4H (ENSG00000270339), PPIAL4E (ENSG00000271567), PPIAL4F (ENSG00000279782), PPIAL4C (ENSG00000288867), PPIAL4D (ENSG00000289549)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase A-like 4G — P0DN37 (reviewed: P0DN37)

Alternative names: Peptidylprolyl cis-trans isomerase A-like 4

All UniProt accessions (1): P0DN37

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_001116540* (*=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-P0DN37-F1	96.40	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, OSMAN_BLOOD_CHAD63_KH_AGE_18_50YO_HIGH_DOSE_SUBJECTS_24HR_DN

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

1924 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPIAL4G	NBPF12	Q5TAG4	986
PPIAL4G	PRSS38	A1L453	478
PPIAL4G	OR2T33	Q8NG76	436
PPIAL4G	LYPD5	Q6UWN5	375
PPIAL4G	TRIML1	Q8N9V2	372
PPIAL4G	ANKRD36	A6QL64	325
PPIAL4G	TAS2R43	P59537	321
PPIAL4G	LRRN2	O75325	308
PPIAL4G	CSAG2	Q9Y5P2	302
PPIAL4G	ACP6	Q9NPH0	300
PPIAL4G	TSPAN31	Q12999	290
PPIAL4G	GPHRA	B7ZAQ6	287
PPIAL4G	ATP13A3	Q9H7F0	263
PPIAL4G	FMO5	P49326	262
PPIAL4G	FKBP1C	Q5VVH2	262

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CACNG2	CCNT1	psi-mi:“MI:0914”(association)	0.530
PPIAL4G	ACTB	psi-mi:“MI:0914”(association)	0.530
TIGD5	P4HA2	psi-mi:“MI:0914”(association)	0.350
QNG1	PPIAL4G	psi-mi:“MI:0914”(association)	0.350
PPIAL4G	PPIAL4D	psi-mi:“MI:0914”(association)	0.350
PPIAL4G	YES1	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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

248 predictions. Top by Δscore:

Variant	Effect	Δscore
1:148483118:T:TA	donor_gain	0.8200
1:148483027:TGTC:T	donor_gain	0.8100
1:148483073:AAAC:A	donor_gain	0.7900
1:148482584:A:C	donor_gain	0.7700
1:148483072:TAA:T	donor_gain	0.7500
1:148483073:AAA:A	donor_gain	0.7500
1:148483127:T:A	donor_gain	0.7400
1:148483211:G:A	donor_gain	0.7300
1:148483025:CTTG:C	donor_gain	0.7200
1:148483026:TTGT:T	donor_gain	0.7200
1:148483116:AAT:A	donor_gain	0.6900
1:148483059:C:CT	donor_gain	0.6500
1:148483100:G:C	donor_gain	0.6500
1:148483123:T:A	donor_gain	0.6300
1:148483137:AGAG:A	donor_gain	0.6200
1:148483115:AAAT:A	donor_gain	0.6100
1:148483088:T:TA	donor_gain	0.6000
1:148483102:AAC:A	donor_gain	0.6000
1:148482896:AGT:A	donor_gain	0.5900
1:148482896:A:AC	donor_gain	0.5800
1:148482921:TGGG:T	donor_gain	0.5800
1:148482999:T:C	donor_gain	0.5800
1:148483062:C:A	donor_gain	0.5700
1:148482881:G:A	donor_gain	0.5600
1:148483104:C:A	donor_gain	0.5600
1:148483180:A:AC	donor_gain	0.5600
1:148483181:C:CC	donor_gain	0.5600
1:148482583:A:AC	donor_gain	0.5500
1:148483013:C:A	donor_gain	0.5500
1:148483102:A:AT	donor_gain	0.5500

AlphaMissense

1108 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:148482866:A:C	F129L	0.769
1:148482866:A:T	F129L	0.769
1:148482868:A:G	F129L	0.769
1:148482917:A:C	F112L	0.768
1:148482917:A:T	F112L	0.768
1:148482919:A:G	F112L	0.768
1:148483073:A:C	F60L	0.759
1:148483073:A:T	F60L	0.759
1:148483075:A:G	F60L	0.759
1:148483004:A:C	F83L	0.731
1:148483004:A:T	F83L	0.731
1:148483006:A:G	F83L	0.731
1:148483094:A:C	F53L	0.721
1:148483094:A:T	F53L	0.721
1:148483096:A:G	F53L	0.721
1:148483232:A:C	F7L	0.701
1:148483232:A:T	F7L	0.701
1:148483234:A:G	F7L	0.701
1:148483052:G:C	F67L	0.644
1:148483052:G:T	F67L	0.644
1:148483054:A:G	F67L	0.644
1:148483115:A:C	F46L	0.641
1:148483115:A:T	F46L	0.641
1:148483117:A:G	F46L	0.641
1:148482914:G:C	F113L	0.639
1:148482914:G:T	F113L	0.639
1:148482916:A:G	F113L	0.639
1:148483145:A:C	F36L	0.634
1:148483145:A:T	F36L	0.634
1:148483147:A:G	F36L	0.634

dbSNP variants (sampled 300 via entrez): RS111334863 (1:148482247 C>T), RS11485934 (1:148484940 C>A,T), RS11488510 (1:148484988 T>C), RS1156276953 (1:148484389 T>G), RS1156366816 (1:148485033 T>G), RS1156406160 (1:148483666 G>A), RS1156598462 (1:148483349 T>C), RS1158113756 (1:148485282 C>T), RS1159004439 (1:148485217 T>C), RS1159240245 (1:148482538 G>T), RS1160629434 (1:148484005 G>A), RS1160702450 (1:148482257 A>G), RS1160808608 (1:148483565 TTCTTTCTTTCTTTCTTTCTTTCTTTC>T), RS1160827300 (1:148483555 ATTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTC>A,ATTTC,ATTTCTTTC,ATTTCTTTCTTTC,ATTTCTTTCTTTCTTTC,ATTTCTTTCTTTCTTTCTTTC,ATTTCTTTCTTTCTTTCTTTCTTTC,ATTTCTTTCTTTCTTTCTTTCTTTCTTTC,ATTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTC,ATTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTC,ATTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTC,ATTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTC,ATTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTC), RS1161336153 (1:148484691 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)

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
epigallocatechin gallate	decreases expression	1
Caffeine	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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