PFDN1

gene
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Also known as PFD1

Summary

PFDN1 (prefoldin subunit 1, HGNC:8866) is a protein-coding gene on chromosome 5q31.3, encoding Prefoldin subunit 1 (O60925). Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. It is a selective cancer dependency (DepMap: 72.2% of cell lines).

This gene encodes a member of the prefoldin beta subunit family. The encoded protein is one of six subunits of prefoldin, a molecular chaperone complex that binds and stabilizes newly synthesized polypeptides, thereby allowing them to fold correctly. The complex, consisting of two alpha and four beta subunits, forms a double beta barrel assembly with six protruding coiled-coils.

Source: NCBI Gene 5201 — RefSeq curated summary.

At a glance

  • GWAS associations: 5
  • Clinical variants (ClinVar): 18 total
  • Druggable target: yes
  • Cancer dependency (DepMap): dependent in 72.2% of screened cell lines
  • MANE Select transcript: NM_002622

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:8866
Approved symbolPFDN1
Nameprefoldin subunit 1
Location5q31.3
Locus typegene with protein product
StatusApproved
AliasesPFD1
Ensembl geneENSG00000113068
Ensembl biotypeprotein_coding
OMIM604897
Entrez5201

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000261813, ENST00000507185, ENST00000510217, ENST00000512707, ENST00000512925, ENST00000514611, ENST00000524074, ENST00000893784, ENST00000934220

RefSeq mRNA: 1 — MANE Select: NM_002622 NM_002622

CCDS: CCDS4222

Canonical transcript exons

ENST00000261813 — 4 exons

ExonStartEnd
ENSE00001254110140245035140246057
ENSE00002021425140303041140303101
ENSE00003586707140281449140281533
ENSE00003685183140300416140300582

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.9297 / max 1373.9073, expressed in 1815 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter IDTPM avgSamples expressed
6378571.92971815

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
calcaneal tendonUBERON:000370197.88gold quality
ganglionic eminenceUBERON:000402396.89gold quality
ventricular zoneUBERON:000305396.70gold quality
hindlimb stylopod muscleUBERON:000425296.68gold quality
islet of LangerhansUBERON:000000696.63gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099196.47gold quality
prefrontal cortexUBERON:000045196.35gold quality
C1 segment of cervical spinal cordUBERON:000646996.33gold quality
apex of heartUBERON:000209896.31gold quality
right frontal lobeUBERON:000281096.27gold quality
cortical plateUBERON:000534396.15gold quality
cingulate cortexUBERON:000302795.97gold quality
heart left ventricleUBERON:000208495.92gold quality
anterior cingulate cortexUBERON:000983595.89gold quality
Brodmann (1909) area 9UBERON:001354095.83gold quality
cardiac ventricleUBERON:000208295.82gold quality
right atrium auricular regionUBERON:000663195.63gold quality
amygdalaUBERON:000187695.53gold quality
smooth muscle tissueUBERON:000113595.52gold quality
nucleus accumbensUBERON:000188295.47gold quality
spinal cordUBERON:000224095.46gold quality
muscle of legUBERON:000138395.45gold quality
caudate nucleusUBERON:000187395.37gold quality
putamenUBERON:000187495.36gold quality
heartUBERON:000094895.25gold quality
gastrocnemiusUBERON:000138895.14gold quality
dorsolateral prefrontal cortexUBERON:000983495.10gold quality
cardiac atriumUBERON:000208194.94gold quality
neocortexUBERON:000195094.91gold quality
lower esophagus muscularis layerUBERON:003583394.91gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes12.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting PFDN1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4283100.0066.422097
HSA-MIR-480399.9871.993117
HSA-MIR-302C-5P99.9772.563642
HSA-MIR-6888-3P99.9765.951170
HSA-MIR-1-3P99.9372.351914
HSA-MIR-20699.9372.501893
HSA-MIR-450B-5P99.9271.483175
HSA-MIR-61399.9171.501710
HSA-MIR-449299.8768.253611
HSA-MIR-4728-5P99.8569.394718
HSA-MIR-6785-5P99.8268.684428
HSA-MIR-149-3P99.7268.223963
HSA-MIR-6883-5P99.6968.053785
HSA-MIR-6892-3P99.6866.401178
HSA-MIR-320299.6667.702737
HSA-MIR-613499.6365.681537
HSA-MIR-466399.6265.33957
HSA-MIR-451699.6167.783390
HSA-MIR-1207-5P99.4969.112983
HSA-MIR-5584-5P99.4968.222814
HSA-MIR-449899.4767.422360
HSA-MIR-318299.4068.152454
HSA-MIR-751599.3168.221795
HSA-MIR-450599.2767.812678
HSA-MIR-4685-5P99.2565.991563
HSA-MIR-6837-5P99.2565.471632
HSA-MIR-797499.2465.481137
HSA-MIR-578799.2267.862628
HSA-MIR-4763-3P99.1067.832649
HSA-MIR-939-3P98.9765.072347

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 72.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

  • antagonistic actions of PhLP3 and prefoldin serve to modulate CCT activity and play a key role in establishing a functional cytoskeleton in vivo (PMID:16415341)
  • Studied PFDN1 as prognosis indicator for colorectal cancer and investigated the functions of PFDN1 in colorectal cancer. (PMID:26553318)
  • High PFDN1 expression is associated with lung cancer progression. (PMID:27694898)
  • Genome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)-based tests (P < 5 x 10(-8)) were identified for SNPs in PFDN1/HBEGF, USP6NL/ECHDC3, and BZRAP1-AS1. (PMID:28183528)
  • Prefoldin and prefoldin-like complex subunits as predictive biomarkers for hepatocellular carcinoma immunotherapy. (PMID:35217267)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriopfdn1ENSDARG00000014536
mus_musculusPfdn1ENSMUSG00000024346
rattus_norvegicusPfdn1ENSRNOG00000018653
drosophila_melanogasterPfdn1FBGN0031776
caenorhabditis_elegansWBGENE00007443

Protein

Protein identifiers

Prefoldin subunit 1O60925 (reviewed: O60925)

All UniProt accessions (3): D6RGG5, E5RGS4, O60925

UniProt curated annotations — full annotation on UniProt →

Function. Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins.

Subunit / interactions. Heterohexamer of two PFD-alpha type and four PFD-beta type subunits.

Similarity. Belongs to the prefoldin subunit beta family.

RefSeq proteins (1): NP_002613* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR002777PFD_beta-likeFamily
IPR009053PrefoldinHomologous_superfamily

Pfam: PF01920

UniProt features (5 total): sequence conflict 2, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

6 structures.

PDBMethodResolution (Å)
7WU7ELECTRON MICROSCOPY3.85
6NR8ELECTRON MICROSCOPY7.8
6NRDELECTRON MICROSCOPY8.2
6NRCELECTRON MICROSCOPY8.3
6NR9ELECTRON MICROSCOPY8.5
6NRBELECTRON MICROSCOPY8.7

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O60925-F193.330.86

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-389957Prefoldin mediated transfer of substrate to CCT/TriC

MSigDB gene sets: 121 (showing top): TGCGCANK_UNKNOWN, GGGTGGRR_PAX4_03, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_PROTEIN_MATURATION, GOBP_PROTEIN_STABILIZATION, GOBP_PROTEIN_FOLDING, GARY_CD5_TARGETS_DN, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, PEART_HDAC_PROLIFERATION_CLUSTER_DN, MORF_PML, MORF_IKBKG, TGGAAA_NFAT_Q4_01, chr5q31, BLALOCK_ALZHEIMERS_DISEASE_DN

GO Biological Process (2): protein folding (GO:0006457), negative regulation of amyloid fibril formation (GO:1905907)

GO Molecular Function (4): amyloid-beta binding (GO:0001540), protein folding chaperone (GO:0044183), obsolete unfolded protein binding (GO:0051082), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), prefoldin complex (GO:0016272), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular process1
protein maturation1
negative regulation of protein metabolic process1
negative regulation of supramolecular fiber organization1
regulation of amyloid fibril formation1
amyloid fibril formation1
peptide binding1
molecular_function1
protein folding1
binding1
intracellular anatomical structure1
cellular anatomical structure1
protein-containing complex1
cellular_component1

Protein interactions and networks

STRING

1834 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
PFDN1VBP1P61758993
PFDN1PFDN4Q9NQP4986
PFDN1PFDN2Q9UHV9986
PFDN1PFDN5Q99471980
PFDN1PFDN6O15212962
PFDN1ACTBL2Q562R1786
PFDN1TCP1P17987716
PFDN1PFN1P07737635
PFDN1CCT3P49368607
PFDN1UXTQ9UBK9572
PFDN1YEATS4O95619538
PFDN1URI1O94763536
PFDN1TBCAO75347517
PFDN1HBEGFQ99075477
PFDN1ACTBP02570473

IntAct

136 interactions, top by confidence:

ABTypeScore
PRKAG3PRKAB2psi-mi:“MI:0914”(association)0.800
GIT1PFDN1psi-mi:“MI:0915”(physical association)0.750
PFDN2PFDN1psi-mi:“MI:0915”(physical association)0.740
PFDN1PFDN2psi-mi:“MI:0915”(physical association)0.740
PFDN4PFDN6psi-mi:“MI:0914”(association)0.730
VBP1PFDN6psi-mi:“MI:0914”(association)0.640
MAPK7PFDN6psi-mi:“MI:0914”(association)0.640
CCT2PPP6Cpsi-mi:“MI:0914”(association)0.640
PFDN1PFDN6psi-mi:“MI:0914”(association)0.640
GNB1GNG7psi-mi:“MI:0914”(association)0.640
DCAF12L2CETN3psi-mi:“MI:0914”(association)0.640
DCAF7PFDN6psi-mi:“MI:0914”(association)0.570
PFDN1DMAP1psi-mi:“MI:0915”(physical association)0.560
IMMTPFDN1psi-mi:“MI:0915”(physical association)0.550
GNB2PFDN6psi-mi:“MI:0914”(association)0.530
DCAF5PFDN6psi-mi:“MI:0914”(association)0.530
KLHDC2PFDN1psi-mi:“MI:0914”(association)0.530
HDAC1PFDN6psi-mi:“MI:0914”(association)0.530
SKIC8PFDN6psi-mi:“MI:0914”(association)0.530
CCT6ATXNDC9psi-mi:“MI:0914”(association)0.530
ELSPBP1PFDN1psi-mi:“MI:0914”(association)0.530
PFDN1ARHGAP32psi-mi:“MI:0914”(association)0.530

BioGRID (273): PFDN1 (Co-fractionation), PFDN2 (Co-fractionation), PFDN5 (Co-fractionation), PFDN6 (Co-fractionation), VBP1 (Co-fractionation), PFDN1 (Proximity Label-MS), PFDN1 (Proximity Label-MS), PFDN1 (Proximity Label-MS), PFDN1 (Affinity Capture-MS), PFDN1 (Affinity Capture-MS), PFDN1 (Affinity Capture-MS), PFDN1 (Affinity Capture-MS), PFDN1 (Affinity Capture-MS), PFDN1 (Affinity Capture-MS), PFDN1 (Affinity Capture-MS)

ESM2 similar proteins: A1A4P5, A7Y521, B0BN18, D3ZKU7, E2R766, F1LMZ8, F1LSG8, O00231, O08522, O55102, O60925, O70591, O75347, O88544, O94826, P48427, P48428, P80585, P97834, Q13098, Q2KI42, Q2NKW0, Q2TBU3, Q32L19, Q3SZ60, Q3SZA0, Q3SZE2, Q3T075, Q4R5E6, Q4SPU8, Q5D016, Q5RAM7, Q5RBL6, Q5ZKV9, Q5ZL19, Q61187, Q6I9Y2, Q6IRE4, Q6NRT5, Q6PEC1

Diamond homologs: O60925, Q17827, Q3SZE2, Q4SPU8, Q5D016, Q5RAM7, Q61SU8, Q94AF7, Q9CWM4, O14334, P46988, Q54JS0

SIGNOR signaling

1 interactions.

AEffectBMechanism
PFDN1“form complex”“Prefoldin co-chaperone”binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
Prefoldin mediated transfer of substrate to CCT/TriC1145.6×1e-13
Formation of tubulin folding intermediates by CCT/TriC940.1×2e-10
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding938.6×2e-10
Chaperonin-mediated protein folding928.5×3e-09
Activation of AMPK downstream of NMDARs728.1×3e-07
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding825.3×7e-08
Protein folding924.6×9e-09
Selective autophagy720.5×3e-06

GO biological processes:

GO termPartnersFoldFDR
positive regulation of telomere maintenance via telomerase531.1×1e-04
mitotic spindle organization511.5×7e-03
mitotic cell cycle89.1×4e-04
protein folding108.8×7e-05
microtubule cytoskeleton organization88.2×7e-04
protein stabilization116.2×3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance9
Likely benign1
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

655 predictions. Top by Δscore:

VariantEffectΔscore
5:140246053:TTCTG:Tacceptor_gain1.0000
5:140246055:CTG:Cacceptor_gain1.0000
5:140246058:C:CCacceptor_gain1.0000
5:140281442:AACTT:Adonor_loss1.0000
5:140281443:ACTT:Adonor_loss1.0000
5:140281444:CTTAC:Cdonor_loss1.0000
5:140281445:TTACT:Tdonor_loss1.0000
5:140281446:TA:Tdonor_loss1.0000
5:140281447:A:ACdonor_gain1.0000
5:140281447:ACT:Adonor_loss1.0000
5:140281447:ACTT:Adonor_gain1.0000
5:140281448:C:Adonor_loss1.0000
5:140281448:C:CAdonor_gain1.0000
5:140281448:CT:Cdonor_gain1.0000
5:140281448:CTT:Cdonor_gain1.0000
5:140281448:CTTC:Cdonor_gain1.0000
5:140281448:CTTCT:Cdonor_gain1.0000
5:140281450:T:TAdonor_gain1.0000
5:140281529:TAAAC:Tacceptor_gain1.0000
5:140281530:AAAC:Aacceptor_gain1.0000
5:140281531:AAC:Aacceptor_gain1.0000
5:140281533:CC:Cacceptor_loss1.0000
5:140281533:CCTA:Cacceptor_gain1.0000
5:140281534:C:CAacceptor_loss1.0000
5:140281534:C:CCacceptor_gain1.0000
5:140281536:A:Cacceptor_gain1.0000
5:140300410:ACTT:Adonor_loss1.0000
5:140300412:TTAC:Tdonor_loss1.0000
5:140300413:TACAT:Tdonor_loss1.0000
5:140300414:A:ACdonor_gain1.0000

AlphaMissense

810 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
5:140246021:C:GA108P1.000
5:140281530:A:CF68L1.000
5:140281530:A:TF68L1.000
5:140281532:A:GF68L1.000
5:140246005:C:GR113P0.999
5:140281531:A:GF68S0.999
5:140300422:C:TG65E0.999
5:140300506:A:GL37P0.999
5:140300569:A:GL16P0.999
5:140300577:G:CF13L0.999
5:140300577:G:TF13L0.999
5:140300578:A:GF13S0.999
5:140300579:A:GF13L0.999
5:140303048:A:GL9P0.999
5:140245996:A:GL116P0.998
5:140245999:A:GM115T0.998
5:140246008:A:CI112S0.998
5:140246008:A:TI112N0.998
5:140246041:A:GL101P0.998
5:140281453:A:GL94P0.998
5:140281495:A:GL80P0.998
5:140300418:T:AR66S0.998
5:140300418:T:GR66S0.998
5:140300419:C:GR66T0.998
5:140300422:C:AG65V0.998
5:140300423:C:GG65R0.998
5:140300423:C:TG65R0.998
5:140300435:A:CY61D0.998
5:140300479:A:GL46P0.998
5:140300486:C:GA44P0.998

dbSNP variants (sampled 300 via entrez): RS1000058291 (5:140278453 C>G), RS1000184013 (5:140272324 T>A,C), RS1000299545 (5:140278760 G>C), RS1000323924 (5:140265286 G>A), RS1000360692 (5:140254152 A>C), RS1000376549 (5:140264960 A>C), RS1000449686 (5:140268674 TACTC>T), RS1000450364 (5:140302551 C>A), RS1000572815 (5:140273381 G>A), RS1000639290 (5:140272147 G>A), RS1000692913 (5:140266981 A>C), RS1000790080 (5:140281353 T>A,C), RS1000846859 (5:140274308 CAT>C), RS1000869100 (5:140251603 C>T), RS1000935433 (5:140259695 A>C)

Disease associations

OMIM: gene MIM:604897 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

StudyTraitp-value
GCST002817_7Alzheimer’s disease in APOE e4- carriers3.000000e-07
GCST004246_1Alzheimer’s disease7.000000e-09
GCST006268_511Reaction time2.000000e-09
GCST008103_180Bipolar disorder9.000000e-06
GCST008115_56Bipolar I disorder8.000000e-07

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0008393reaction time measurement
EFO:0009963bipolar I disorder

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067021 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
6.78Kd165.4nMCHEMBL5653589
6.49ED50326.7nMCHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2148979: Binding affinity to human PFDN1 incubated for 45 mins by Kinobead based pull down assaykd0.1654uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

ChemicalActions (top 5)PubMed papers
Aflatoxin B1decreases methylation, increases methylation2
aristolochic acid Iincreases expression1
alpha-pineneaffects cotreatment, increases oxidation, increases abundance1
bisphenol Aincreases expression1
sodium arseniteaffects cotreatment, decreases expression, increases abundance1
manganese chlorideincreases abundance, affects cotreatment, decreases expression1
methacrylaldehydeaffects cotreatment, increases oxidation, increases abundance1
cylindrospermopsinincreases expression1
CGP 52608increases reaction, affects binding1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideincreases expression, affects cotreatment1
ICG 001decreases expression1
quinocetonedecreases expression1
LDN 193189affects cotreatment, increases expression1
(+)-JQ1 compounddecreases expression1
Sunitinibdecreases expression1
Acetaminophenaffects response to substance1
Acroleinaffects cotreatment, increases oxidation, increases abundance1
Air Pollutantsaffects cotreatment, increases abundance, increases oxidation1
Arsenicincreases abundance, affects cotreatment, decreases expression1
Diurondecreases expression1
Ivermectindecreases expression1
Manganesedecreases expression, increases abundance, affects cotreatment1
Ozoneaffects cotreatment, increases oxidation, increases abundance1
Cadmium Chlorideincreases expression1
Volatile Organic Compoundsaffects cotreatment, increases oxidation1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5652021BindingBinding affinity to human PFDN1 incubated for 45 mins by Kinobead based pull down assayNVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.