PFDN4

Summary

PFDN4 (prefoldin subunit 4, HGNC:8868) is a protein-coding gene on chromosome 20q13.2, encoding Prefoldin subunit 4 (Q9NQP4). Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. It is a selective cancer dependency (DepMap: 25.5% 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 5203 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 20 total
• Cancer dependency (DepMap): dependent in 25.5% of screened cell lines
• MANE Select transcript: NM_002623

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8868
Approved symbol	PFDN4
Name	prefoldin subunit 4
Location	20q13.2
Locus type	gene with protein product
Status	Approved
Aliases	PFD4, C-1, C1
Ensembl gene	ENSG00000101132
Ensembl biotype	protein_coding
OMIM	604898
Entrez	5203

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000371419, ENST00000441080, ENST00000474326, ENST00000487129, ENST00000493356, ENST00000715725, ENST00000857809, ENST00000921438, ENST00000921439, ENST00000921440, ENST00000921441, ENST00000921442

RefSeq mRNA: 1 — MANE Select: NM_002623 NM_002623

CCDS: CCDS13445

Canonical transcript exons

ENST00000371419 — 4 exons

Exon	Start	End
ENSE00003580420	54215300	54215440
ENSE00003628363	54214351	54214458
ENSE00004027706	54208087	54208124
ENSE00004027707	54219019	54219961

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.6948 / max 1573.3455, expressed in 1809 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185398	61.8381	1808
185396	1.7747	1045
185395	1.4584	723
185397	0.5618	331
185399	0.0619	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.45	gold quality
ganglionic eminence	UBERON:0004023	97.43	gold quality
cortical plate	UBERON:0005343	97.42	gold quality
embryo	UBERON:0000922	97.21	gold quality
calcaneal tendon	UBERON:0003701	96.63	gold quality
frontal pole	UBERON:0002795	96.49	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.16	gold quality
endometrium epithelium	UBERON:0004811	96.08	gold quality
paraflocculus	UBERON:0005351	96.05	gold quality
superficial temporal artery	UBERON:0001614	95.65	gold quality
ventricular zone	UBERON:0003053	95.39	gold quality
palpebral conjunctiva	UBERON:0001812	95.12	gold quality
secondary oocyte	CL:0000655	95.00	gold quality
adult organism	UBERON:0007023	94.89	gold quality
endometrium	UBERON:0001295	94.68	gold quality
biceps brachii	UBERON:0001507	94.61	gold quality
middle frontal gyrus	UBERON:0002702	94.39	gold quality
oral cavity	UBERON:0000167	94.20	gold quality
cingulate cortex	UBERON:0003027	94.17	gold quality
anterior cingulate cortex	UBERON:0009835	94.16	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.13	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.03	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.96	gold quality
cauda epididymis	UBERON:0004360	93.88	gold quality
prefrontal cortex	UBERON:0000451	93.85	gold quality
germinal epithelium of ovary	UBERON:0001304	93.85	gold quality
left testis	UBERON:0004533	93.84	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.76	gold quality
substantia nigra pars compacta	UBERON:0001965	93.70	gold quality
islet of Langerhans	UBERON:0000006	93.67	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.15
E-MTAB-7316	yes	7.12
E-MTAB-9388	no	426.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF3, BCL6, TWIST1, TWIST2

miRNA regulators (miRDB)

71 targeting PFDN4, 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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 25.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• PFDN4 inhibition resulted in an increase in cell growth and invasiveness in colorectal cancer cell lines. (PMID:20552408)
• Novel long noncoding RNAs upregulation may have synergistic effects on the CYP24A1 and PFDN4 biomarker role in human colorectal cancer. (PMID:32743796)
• PFDN4 as a Prognostic Marker Was Associated with Chemotherapy Resistance through CREBP1/AURKA Pathway in Triple-Negative Breast Cancer. (PMID:38612711)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pfdn4	ENSDARG00000061228
mus_musculus	Pfdn4	ENSMUSG00000052033
rattus_norvegicus	Pfdn4	ENSRNOG00000050932
drosophila_melanogaster	Pfdn4	FBGN0035603
caenorhabditis_elegans		WBGENE00007107

Protein

Protein identifiers

Prefoldin subunit 4 — Q9NQP4 (reviewed: Q9NQP4)

Alternative names: Protein C-1

All UniProt accessions (2): Q9NQP4, E9PQY2

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. Interacts with URI1; the interaction is phosphorylation-dependent and occurs in a growth-dependent manner.

Subcellular location. Nucleus. Cytoplasm. Mitochondrion.

Similarity. Belongs to the prefoldin subunit beta family.

RefSeq proteins (1): NP_002614* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002777	PFD_beta-like	Family
IPR009053	Prefoldin	Homologous_superfamily
IPR016661	PFDN4	Family

Pfam: PF01920

UniProt features (4 total): modified residue 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7WU7	ELECTRON MICROSCOPY	3.85
6NR8	ELECTRON MICROSCOPY	7.8
6NRD	ELECTRON MICROSCOPY	8.2
6NRC	ELECTRON MICROSCOPY	8.3
6NR9	ELECTRON MICROSCOPY	8.5
6NRB	ELECTRON MICROSCOPY	8.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQP4-F1	88.22	0.75

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 (2): 2, 125

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 168 (showing top): WENDT_COHESIN_TARGETS_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MODULE_493, MODULE_503, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, PUJANA_CHEK2_PCC_NETWORK, MODULE_331, GOBP_PROTEIN_MATURATION, MODULE_195, GAZDA_DIAMOND_BLACKFAN_ANEMIA_PROGENITOR_DN, GOBP_PROTEIN_FOLDING, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP

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), obsolete unfolded protein binding (GO:0051082), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), prefoldin complex (GO:0016272), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cytoplasm	2
cellular process	1
protein maturation	1
negative regulation of protein metabolic process	1
negative regulation of supramolecular fiber organization	1
regulation of amyloid fibril formation	1
amyloid fibril formation	1
peptide binding	1
protein binding	1
binding	1
intracellular anatomical structure	1
protein-containing complex	1
cellular_component	1

Protein interactions and networks

STRING

1764 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PFDN4	PFDN5	Q99471	987
PFDN4	PFDN1	O60925	986
PFDN4	PFDN2	Q9UHV9	986
PFDN4	VBP1	P61758	980
PFDN4	PFDN6	O15212	922
PFDN4	URI1	O94763	868
PFDN4	POLR2E	P19388	860
PFDN4	RUVBL1	P82276	780
PFDN4	RUVBL2	Q9Y230	751
PFDN4	TENT4A	Q5XG87	668
PFDN4	C1R	P00736	636
PFDN4	C1S	P09871	627
PFDN4	CHORDC1	Q9UHD1	623
PFDN4	SERPING1	P05155	608
PFDN4	SHC4	Q6S5L8	587

IntAct

77 interactions, top by confidence:

A	B	Type	Score
VBP1	PFDN4	psi-mi:“MI:0915”(physical association)	0.870
PFDN4	VBP1	psi-mi:“MI:0915”(physical association)	0.870
CHAF1B	CBX5	psi-mi:“MI:0914”(association)	0.790
PFDN4	PFDN6	psi-mi:“MI:0914”(association)	0.730
DDB2	CCT2	psi-mi:“MI:0914”(association)	0.730
DCAF7	DIAPH1	psi-mi:“MI:0914”(association)	0.730
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
PFDN1	PFDN6	psi-mi:“MI:0914”(association)	0.640
DDB2	CCT5	psi-mi:“MI:0914”(association)	0.640
DCAF12L2	CETN3	psi-mi:“MI:0914”(association)	0.640
DCAF7	PFDN6	psi-mi:“MI:0914”(association)	0.570
RFPL3	PFDN4	psi-mi:“MI:0915”(physical association)	0.560
GNB2	PFDN6	psi-mi:“MI:0914”(association)	0.530
DCAF5	PFDN6	psi-mi:“MI:0914”(association)	0.530
SPATA2	CASK	psi-mi:“MI:0914”(association)	0.530
SKIC8	PFDN6	psi-mi:“MI:0914”(association)	0.530
PFDN1	ARHGAP32	psi-mi:“MI:0914”(association)	0.530
WSB2	BCL2L1	psi-mi:“MI:0914”(association)	0.530
TUBA3E	PFDN6	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (211): PFDN4 (Affinity Capture-MS), VBP1 (Two-hybrid), PFDN4 (Affinity Capture-MS), PFDN4 (Affinity Capture-MS), PFDN4 (Affinity Capture-MS), EIF6 (Co-fractionation), FLNA (Co-fractionation), GFPT1 (Co-fractionation), MSH2 (Co-fractionation), PFDN1 (Co-fractionation), PFDN2 (Co-fractionation), PFDN4 (Co-fractionation), PFDN4 (Co-fractionation), PFDN4 (Co-fractionation), PFDN4 (Co-fractionation)

ESM2 similar proteins: A8IVX2, A8WVJ9, A8X0Z1, A8XPL7, G5EES6, O13754, O14334, O18054, O94307, O94393, O94721, P33313, P40005, P40555, P46988, P48363, P48606, P53900, P61758, P61759, P87157, Q02328, Q09739, Q09746, Q10143, Q17435, Q17750, Q17827, Q17886, Q1MTN8, Q21993, Q2TBR6, Q2TBX2, Q54JS0, Q54LS2, Q54TB7, Q5RCG9, Q61SU8, Q75JC8, Q9HGK2

Diamond homologs: A8X0Z1, Q17435, Q2TBR6, Q9M4B5, Q9M4C4, Q9NQP4, Q9UTD4, P53900, Q54TB7, Q9VRL3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
TWIST2	“down-regulates quantity by repression”	PFDN4	“transcriptional regulation”
TWIST1	“down-regulates quantity by repression”	PFDN4	“transcriptional regulation”
PFDN4	“form complex”	“Prefoldin co-chaperone”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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:

Pathway	Partners	Fold	FDR
Prefoldin mediated transfer of substrate to CCT/TriC	7	51.0×	2e-08
Formation of tubulin folding intermediates by CCT/TriC	6	47.0×	5e-07
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	6	45.3×	5e-07
Activation of AMPK downstream of NMDARs	5	35.2×	1e-05
Chaperonin-mediated protein folding	6	33.4×	2e-06
Protein folding	6	28.8×	4e-06
Cargo trafficking to the periciliary membrane	6	27.6×	5e-06
Selective autophagy	5	25.8×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
smoothened signaling pathway	5	12.4×	9e-03
microtubule cytoskeleton organization	6	10.0×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

716 predictions. Top by Δscore:

Variant	Effect	Δscore
20:54214347:TCA:T	acceptor_loss	1.0000
20:54214349:A:AG	acceptor_gain	1.0000
20:54214349:A:AT	acceptor_loss	1.0000
20:54214349:AG:A	acceptor_gain	1.0000
20:54214350:G:GA	acceptor_gain	1.0000
20:54214350:GG:G	acceptor_gain	1.0000
20:54214350:GGC:G	acceptor_gain	1.0000
20:54214350:GGCT:G	acceptor_gain	1.0000
20:54214438:G:GT	donor_gain	1.0000
20:54214447:G:GT	donor_gain	1.0000
20:54214457:AG:A	donor_loss	1.0000
20:54214458:GG:G	donor_loss	1.0000
20:54214459:GT:G	donor_loss	1.0000
20:54214460:T:A	donor_loss	1.0000
20:54215293:T:G	acceptor_gain	1.0000
20:54215295:TATA:T	acceptor_loss	1.0000
20:54215296:ATAG:A	acceptor_loss	1.0000
20:54215298:A:AG	acceptor_gain	1.0000
20:54215298:A:T	acceptor_loss	1.0000
20:54215299:G:GT	acceptor_gain	1.0000
20:54215299:GA:G	acceptor_gain	1.0000
20:54215299:GAAAC:G	acceptor_gain	1.0000
20:54215441:G:GG	donor_gain	1.0000
20:54215442:T:A	donor_loss	1.0000
20:54219013:TTCCA:T	acceptor_loss	1.0000
20:54219014:TCCA:T	acceptor_loss	1.0000
20:54219015:CCA:C	acceptor_loss	1.0000
20:54219016:CAG:C	acceptor_loss	1.0000
20:54219017:A:AG	acceptor_gain	1.0000
20:54219017:A:AT	acceptor_loss	1.0000

AlphaMissense

907 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:54214386:A:C	Q20H	1.000
20:54214386:A:T	Q20H	1.000
20:54214394:T:C	I23T	1.000
20:54214402:T:C	F26L	1.000
20:54214404:T:A	F26L	1.000
20:54214404:T:G	F26L	1.000
20:54219101:T:C	L119S	1.000
20:54219112:T:C	F123L	1.000
20:54219113:T:C	F123S	1.000
20:54219114:C:A	F123L	1.000
20:54219114:C:G	F123L	1.000
20:54219125:T:A	I127K	1.000
20:54219125:T:C	I127T	1.000
20:54219131:T:A	L129H	1.000
20:54219131:T:C	L129P	1.000
20:54214370:T:A	V15D	0.999
20:54214370:T:C	V15A	0.999
20:54214381:G:C	D19H	0.999
20:54214385:A:C	Q20P	0.999
20:54214388:A:C	Q21P	0.999
20:54214394:T:A	I23K	0.999
20:54214403:T:C	F26S	0.999
20:54214403:T:G	F26C	0.999
20:54214405:G:C	A27P	0.999
20:54214406:C:A	A27E	0.999
20:54214409:G:C	R28P	0.999
20:54214433:T:C	L36P	0.999
20:54215316:T:C	L50P	0.999
20:54215324:G:C	A53P	0.999
20:54215325:C:A	A53D	0.999

dbSNP variants (sampled 300 via entrez): RS1000341641 (20:54208452 G>A), RS1000543207 (20:54218481 T>C), RS1000658076 (20:54218883 A>G), RS1000679950 (20:54212539 A>C,G,T), RS1000733405 (20:54206720 A>G), RS1000733451 (20:54212822 A>G), RS1000943646 (20:54207229 T>C), RS1000987322 (20:54212086 G>C), RS1001018526 (20:54218993 A>G), RS1001250022 (20:54206895 T>C), RS1001593290 (20:54210925 G>A), RS1001683464 (20:54211209 A>G), RS1001734295 (20:54211368 A>G), RS1001960632 (20:54211159 T>C), RS1001975196 (20:54217156 A>C,T)

Disease associations

OMIM: gene MIM:604898 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001709_17	Atopic dermatitis	2.000000e-08
GCST001762_416	Obesity-related traits	5.000000e-06
GCST003659_11	Modified Stumvoll Insulin Sensitivity Index (BMI interaction)	2.000000e-09
GCST007877_24	Creatinine levels	1.000000e-08
GCST010219_21	Attention deficit hyperactivity disorder (inattention symptoms)	3.000000e-07
GCST011743_7	HDL cholesterol levels in HIV infection	7.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0003940	physical activity
EFO:0004340	body mass index
EFO:0004471	insulin sensitivity measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	3
Air Pollutants	decreases expression, affects expression, increases abundance	2
Valproic Acid	decreases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
bisphenol A	increases expression	1
arsenite	affects binding, increases reaction	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
avobenzone	increases expression	1
oligofectamine	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression, affects cotreatment	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression, increases abundance	1
Thimerosal	increases expression	1

Clinical trials (associated diseases)

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