PPIAL4D

Summary

PPIAL4D (peptidylprolyl isomerase A like 4D, HGNC:33998) is a protein-coding gene on chromosome 1q21.1, encoding Peptidyl-prolyl cis-trans isomerase A-like 4D (F5H284). 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 645142 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 5 total — 1 pathogenic
• MANE Select transcript: NM_001164261

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33998
Approved symbol	PPIAL4D
Name	peptidylprolyl isomerase A like 4D
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000289549
Ensembl biotype	protein_coding
Entrez	645142

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000544708

RefSeq mRNA: 1 — MANE Select: NM_001164261 NM_001164261

CCDS: CCDS59199

Canonical transcript exons

ENST00000544708 — 1 exons

Exon	Start	End
ENSE00002226693	145241415	145242174

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 PPIAL4D, 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-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-335-5P	97.10	68.12	1022
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), PPIAL4C (ENSG00000288867)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase A-like 4D — F5H284 (reviewed: F5H284)

All UniProt accessions (1): F5H284

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_001157733* (*=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-F5H284-F1	96.60	0.98

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 12 (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, 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

1818 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPIAL4D	SPATA31A5	Q5VU36	720
PPIAL4D	TRIM64B	A6NI03	604
PPIAL4D	FAM131C	Q96AQ9	570
PPIAL4D	NBPF12	Q5TAG4	482
PPIAL4D	NBPF11	Q86T75	478
PPIAL4D	NBPF14	Q5TI25	477
PPIAL4D	CCDC124	Q96CT7	466
PPIAL4D	NBPF15	Q8N660	449
PPIAL4D	ACP6	Q9NPH0	373
PPIAL4D	FMO5	P49326	348
PPIAL4D	NOTCH2NLB	P0DPK3	328
PPIAL4D	NUP43	Q8NFH3	322
PPIAL4D	CLCNKB	P51801	305
PPIAL4D	NBPF10	Q6P3W6	303
PPIAL4D	AKR1C4	P17516	293
PPIAL4D	HYDIN	Q4G0P3	293

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PPIAL4G	PPIAL4D	psi-mi:“MI:0914”(association)	0.350
SGK1	PPIAL4D	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (1): PPIAL4D (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

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
997084	GRCh37/hg19 1q21.1-21.2(chr1:145818702-149378266)	Pathogenic

SpliceAI

170 predictions. Top by Δscore:

Variant	Effect	Δscore
1:145241990:T:TA	donor_gain	0.7700
1:145241999:T:A	donor_gain	0.7700
1:145241899:TGTC:T	donor_gain	0.7600
1:145241456:A:C	donor_gain	0.7100
1:145241944:TAA:T	donor_gain	0.7100
1:145241945:AAA:A	donor_gain	0.7100
1:145241945:AAAC:A	donor_gain	0.7000
1:145241897:CTTG:C	donor_gain	0.6900
1:145241898:TTGT:T	donor_gain	0.6900
1:145241972:G:C	donor_gain	0.6800
1:145241987:AAAT:A	donor_gain	0.6300
1:145241974:A:AT	donor_gain	0.6200
1:145241931:C:CT	donor_gain	0.6000
1:145241988:AAT:A	donor_gain	0.5900
1:145241995:T:A	donor_gain	0.5900
1:145241974:AAC:A	donor_gain	0.5800
1:145241793:TGGG:T	donor_gain	0.5700
1:145241976:C:A	donor_gain	0.5700
1:145242009:AGAG:A	donor_gain	0.5700
1:145241451:A:C	donor_gain	0.5600
1:145241960:T:TA	donor_gain	0.5600
1:145241975:AC:A	donor_gain	0.5500
1:145241977:CC:C	donor_gain	0.5400
1:145241934:C:A	donor_gain	0.5300
1:145241978:C:T	donor_gain	0.5300
1:145242024:T:TA	donor_gain	0.5300
1:145241871:T:C	donor_gain	0.5200
1:145241885:C:A	donor_gain	0.5000
1:145241900:G:GC	donor_gain	0.5000
1:145241932:C:CT	donor_gain	0.5000

AlphaMissense

1100 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:145241945:A:C	F60L	0.812
1:145241945:A:T	F60L	0.812
1:145241947:A:G	F60L	0.812
1:145241738:A:C	F129L	0.795
1:145241738:A:T	F129L	0.795
1:145241740:A:G	F129L	0.795
1:145241789:A:C	F112L	0.779
1:145241789:A:T	F112L	0.779
1:145241791:A:G	F112L	0.779
1:145242104:A:C	F7L	0.779
1:145242104:A:T	F7L	0.779
1:145242106:A:G	F7L	0.779
1:145241876:A:C	F83L	0.776
1:145241876:A:T	F83L	0.776
1:145241878:A:G	F83L	0.776
1:145242017:A:C	F36L	0.734
1:145242017:A:T	F36L	0.734
1:145242019:A:G	F36L	0.734
1:145241987:A:C	F46L	0.695
1:145241987:A:T	F46L	0.695
1:145241989:A:G	F46L	0.695
1:145241924:G:C	F67L	0.694
1:145241924:G:T	F67L	0.694
1:145241926:A:G	F67L	0.694
1:145241966:A:C	F53L	0.689
1:145241966:A:T	F53L	0.689
1:145241968:A:G	F53L	0.689
1:145242050:A:C	F25L	0.683
1:145242050:A:T	F25L	0.683
1:145242052:A:G	F25L	0.683

dbSNP variants (sampled 300 via entrez): RS111960529 (1:145241232 T>A), RS112572112 (1:145241231 A>G,T), RS1156396792 (1:145244123 C>A), RS1157196337 (1:145241060 A>AG), RS1157917655 (1:145242639 C>T), RS1157984229 (1:145241591 A>G), RS1158079667 (1:145243661 C>A), RS1158745696 (1:145241638 G>A), RS1159107648 (1:145242168 A>G), RS1159450128 (1:145241067 T>C), RS1159520499 (1:145242666 G>A), RS1160550613 (1:145241311 A>G), RS1160571232 (1:145241857 G>A,C), RS1160623861 (1:145243255 TACA>T), RS1160916923 (1:145242445 T>C)

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.