CSTF1

Summary

CSTF1 (cleavage stimulation factor subunit 1, HGNC:2483) is a protein-coding gene on chromosome 20q13.2-q13.31, encoding Cleavage stimulation factor subunit 1 (Q05048). One of the multiple factors required for polyadenylation and 3’-end cleavage of mammalian pre-mRNAs. It is a common-essential gene (DepMap: required in 96.4% of cancer cell lines).

This gene encodes one of three subunits which combine to form cleavage stimulation factor (CSTF). CSTF is involved in the polyadenylation and 3’end cleavage of pre-mRNAs. Similar to mammalian G protein beta subunits, this protein contains transducin-like repeats. Several transcript variants with different 5’ UTR, but encoding the same protein, have been found for this gene.

Source: NCBI Gene 1477 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 34 total
• Cancer dependency (DepMap): dependent in 96.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_001324

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2483
Approved symbol	CSTF1
Name	cleavage stimulation factor subunit 1
Location	20q13.2-q13.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000101138
Ensembl biotype	protein_coding
OMIM	600369
Entrez	1477

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000217109, ENST00000415828, ENST00000428552, ENST00000452950, ENST00000490539, ENST00000493039, ENST00000498689, ENST00000613138, ENST00000892721, ENST00000892722, ENST00000892723, ENST00000892724, ENST00000892725, ENST00000892726, ENST00000919355, ENST00000919356

RefSeq mRNA: 3 — MANE Select: NM_001324 NM_001033521, NM_001033522, NM_001324

CCDS: CCDS13452

Canonical transcript exons

ENST00000217109 — 6 exons

Exon	Start	End
ENSE00000845702	56395521	56395721
ENSE00001022804	56392645	56392713
ENSE00003630346	56397207	56397484
ENSE00003657539	56403468	56406362
ENSE00003673962	56397644	56397841
ENSE00003784583	56398967	56399357

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 92.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.4097 / max 296.0451, expressed in 1801 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185415	18.4599	1777
185412	7.7635	1657
185414	1.4900	755
185413	0.6964	389

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.96	gold quality
adrenal tissue	UBERON:0018303	91.56	gold quality
secondary oocyte	CL:0000655	91.34	gold quality
calcaneal tendon	UBERON:0003701	90.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.93	gold quality
islet of Langerhans	UBERON:0000006	89.58	gold quality
stromal cell of endometrium	CL:0002255	89.51	gold quality
ventricular zone	UBERON:0003053	87.46	gold quality
rectum	UBERON:0001052	86.60	gold quality
granulocyte	CL:0000094	86.49	gold quality
body of pancreas	UBERON:0001150	86.36	gold quality
ganglionic eminence	UBERON:0004023	86.26	gold quality
left ovary	UBERON:0002119	86.08	gold quality
pancreas	UBERON:0001264	86.05	gold quality
oocyte	CL:0000023	86.00	gold quality
right adrenal gland	UBERON:0001233	85.96	gold quality
right adrenal gland cortex	UBERON:0035827	85.91	gold quality
muscle of leg	UBERON:0001383	85.75	gold quality
right ovary	UBERON:0002118	85.70	gold quality
gall bladder	UBERON:0002110	85.68	gold quality
right lobe of liver	UBERON:0001114	85.67	gold quality
gastrocnemius	UBERON:0001388	85.63	gold quality
sperm	CL:0000019	85.38	gold quality
testis	UBERON:0000473	85.35	gold quality
left adrenal gland	UBERON:0001234	85.30	gold quality
left adrenal gland cortex	UBERON:0035825	85.25	gold quality
left testis	UBERON:0004533	85.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.87	gold quality
right testis	UBERON:0004534	84.62	gold quality
left uterine tube	UBERON:0001303	84.60	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7249	no	434.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting CSTF1, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-1273H-3P	99.29	67.55	980

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• A deletion variant of BARD1, a BRCA1 partner, occurs in cells and interacts with and colocalizes with CstF-50. (PMID:15878232)
• characterize the BARD1 structural biochemistry responsible for CstF-50 binding (PMID:18842000)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cstf1	ENSDARG00000044820
mus_musculus	Cstf1	ENSMUSG00000027498
rattus_norvegicus	Cstf1	ENSRNOG00000004775
drosophila_melanogaster	CstF50	FBGN0039867
caenorhabditis_elegans		WBGENE00000773

Paralogs (2): IK (ENSG00000113141), WDR55 (ENSG00000120314)

Protein

Protein identifiers

Cleavage stimulation factor subunit 1 — Q05048 (reviewed: Q05048)

Alternative names: CF-1 50 kDa subunit, Cleavage stimulation factor 50 kDa subunit

All UniProt accessions (4): Q05048, A0A087WV92, A0A0A0MSZ9, A3KFI9

UniProt curated annotations — full annotation on UniProt →

Function. One of the multiple factors required for polyadenylation and 3’-end cleavage of mammalian pre-mRNAs. May be responsible for the interaction of CSTF with other factors to form a stable complex on the pre-mRNA.

Subunit / interactions. Homodimer. The CSTF complex is composed of CSTF1 (50 kDa subunit), CSTF2 (64 kDa subunit) and CSTF3 (77 kDa subunit). Interacts (via repeats WD) directly with CSTF3. Interacts (via repeat WD6) with BARD1. Interacts with ERCC6.

Subcellular location. Nucleus.

Post-translational modifications. The N-terminus is blocked.

Domain organisation. N-terminus mediates homodimerization.

RefSeq proteins (3): NP_001028693, NP_001028694, NP_001315* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR032028	CSTF1_dimer	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR038184	CSTF1_dimer_sf	Homologous_superfamily
IPR044633	CstF1-like	Family

Pfam: PF00400, PF16699

UniProt features (44 total): strand 27, repeat 6, turn 6, helix 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6B3X	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05048-F1	90.65	0.77

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-72187	mRNA 3’-end processing
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-77595	Processing of Intronless Pre-mRNAs
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA

MSigDB gene sets: 161 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_MRNA_3_END_PROCESSING, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_MRNA_3_END_PROCESSING, BOYLAN_MULTIPLE_MYELOMA_C_CLUSTER_UP, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, MYB_Q3, YNGTTNNNATT_UNKNOWN, GRADE_COLON_AND_RECTAL_CANCER_UP, REACTOME_METABOLISM_OF_RNA

GO Biological Process (2): mRNA 3’-end processing (GO:0031124), mRNA processing (GO:0006397)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (3): nucleoplasm (GO:0005654), mRNA cleavage stimulating factor complex (GO:0005848), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Processing of Capped Intron-Containing Pre-mRNA	1
RNA Polymerase II Transcription	1
Processing of Capped Intronless Pre-mRNA	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mRNA processing	1
RNA 3’-end processing	1
RNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
mRNA cleavage factor complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSTF1	CSTF2	P33240	999
CSTF1	CSTF3	Q12996	999
CSTF1	BARD1	Q99728	987
CSTF1	BRCA1	P38398	948
CSTF1	CPSF2	Q9P2I0	920
CSTF1	CPSF1	Q10570	919
CSTF1	CPSF3	Q9UKF6	875
CSTF1	CPSF4	O95639	874
CSTF1	PCF11	O94913	873
CSTF1	SYMPK	Q92797	871
CSTF1	CPSF7	Q8N684	804
CSTF1	PAPOLA	P51003	786
CSTF1	PAPOLG	Q9BWT3	783
CSTF1	PAPOLB	Q9NRJ5	780
CSTF1	NUDT21	O43809	776

IntAct

63 interactions, top by confidence:

A	B	Type	Score
TOLLIP	TOM1L1	psi-mi:“MI:0914”(association)	0.800
TOLLIP	CSTF1	psi-mi:“MI:0915”(physical association)	0.760
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
CSTF1	BARD1	psi-mi:“MI:0915”(physical association)	0.580
BARD1	CSTF1	psi-mi:“MI:0915”(physical association)	0.580
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530
RACGAP1	CHEK1	psi-mi:“MI:0914”(association)	0.530
BMP1	TLL1	psi-mi:“MI:0914”(association)	0.530
CSTF2T	CRTAP	psi-mi:“MI:0914”(association)	0.530
TOLLIP	IRAK2	psi-mi:“MI:0914”(association)	0.500
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
POLR1A	CSTF1	psi-mi:“MI:0915”(physical association)	0.400
CSTF1	PCNA	psi-mi:“MI:0915”(physical association)	0.400
GCM2	CSTF1	psi-mi:“MI:0915”(physical association)	0.400
CPSF3	P4HA2	psi-mi:“MI:0914”(association)	0.350
Cct4	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
Cct2	OSBPL9	psi-mi:“MI:0914”(association)	0.350
Cct8	DTL	psi-mi:“MI:0914”(association)	0.350
FIP1L1	WWP2	psi-mi:“MI:0914”(association)	0.350
NS1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
GTF2E2	UBA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (156): CSTF1 (Affinity Capture-MS), CSTF1 (Affinity Capture-MS), CSTF1 (Affinity Capture-MS), CSTF1 (Co-fractionation), CSTF1 (Co-fractionation), CSTF1 (Co-fractionation), CSTF1 (Co-fractionation), CSTF1 (Co-fractionation), CSTF1 (Co-fractionation), CSTF3 (Co-fractionation), DCUN1D1 (Co-fractionation), DLD (Co-fractionation), DNAAF5 (Co-fractionation), HSPBP1 (Co-fractionation), MAPK3 (Co-fractionation)

ESM2 similar proteins: A0JN27, A6H7F7, B2RYU6, B5FXJ6, B5FYY5, B5X7X4, B5XGE7, O43504, P55168, P61201, P61202, P61203, P79101, Q05048, Q13888, Q28F72, Q2TBL9, Q2TBV5, Q2YDH6, Q3T132, Q4KLA0, Q4R9A8, Q4VC33, Q5BJQ6, Q5F398, Q5M8X5, Q5R532, Q5R8K2, Q5R9J9, Q5RKJ1, Q63ZJ2, Q6DEG4, Q6DF40, Q6GR10, Q6IQT4, Q6IR75, Q6P1K8, Q7L5Y9, Q7SXR3, Q7ZXB7

Diamond homologs: A1CF18, A1CUD6, A1DP19, A2QP30, A4R3M4, A7EKM8, A8NEG8, A8XZJ9, A9V790, B0XM00, B2AEZ5, B2B766, B2VWG7, B2VZH2, B3MEY6, B3MHX6, B3NLK7, B3NPW0, B4GAJ1, B4GIU9, B4HN85, B4HSL3, B4JWA1, B4KQU8, B4KT48, B4LQ21, B4MY65, B4MYI5, B4P528, B4P6P9, B4QHG6, B6GZD3, B6HP56, B6QC06, B6QC56, B7FNU7, B8M0Q1, B8N9H4, B8P4B0, B8PD53

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CSTF1	“form complex”	“CSTF complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 78 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
Processing of Intronless Pre-mRNAs	6	52.7×	4e-07
RNA Polymerase II Transcription Termination	7	23.6×	2e-06
mRNA 3’-end processing	7	21.2×	3e-06
mRNA Polyadenylation	10	13.5×	5e-07
Dengue Virus-Host Interactions	10	7.0×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

947 predictions. Top by Δscore:

Variant	Effect	Δscore
20:56392512:G:GT	donor_gain	1.0000
20:56392535:GCCA:G	donor_gain	1.0000
20:56392539:G:GG	donor_gain	1.0000
20:56395519:A:AG	acceptor_gain	1.0000
20:56395519:AGCT:A	acceptor_gain	1.0000
20:56395520:G:GA	acceptor_gain	1.0000
20:56395520:GCT:G	acceptor_gain	1.0000
20:56395520:GCTG:G	acceptor_gain	1.0000
20:56395675:GTCT:G	donor_gain	1.0000
20:56397323:GCTTC:G	donor_gain	1.0000
20:56397638:GTCTA:G	acceptor_loss	1.0000
20:56397639:TCTA:T	acceptor_loss	1.0000
20:56397640:CTA:C	acceptor_loss	1.0000
20:56397641:TAGGT:T	acceptor_loss	1.0000
20:56397642:AGGTC:A	acceptor_loss	1.0000
20:56397643:G:T	acceptor_loss	1.0000
20:56397769:TTC:T	donor_gain	1.0000
20:56397776:G:T	donor_gain	1.0000
20:56392534:TGCCA:T	donor_gain	0.9900
20:56392535:GCCAG:G	donor_gain	0.9900
20:56392543:G:GG	donor_gain	0.9900
20:56395516:TGCAG:T	acceptor_gain	0.9900
20:56395517:GCAGC:G	acceptor_gain	0.9900
20:56395518:CA:C	acceptor_loss	0.9900
20:56395518:CAGCT:C	acceptor_gain	0.9900
20:56395519:AG:A	acceptor_loss	0.9900
20:56395519:AGC:A	acceptor_gain	0.9900
20:56395519:AGCTG:A	acceptor_gain	0.9900
20:56395520:G:A	acceptor_loss	0.9900
20:56395520:G:T	acceptor_gain	0.9900

AlphaMissense

2833 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:56395617:T:C	L22P	1.000
20:56395644:C:A	A31D	1.000
20:56397344:T:C	Y103H	1.000
20:56397344:T:G	Y103D	1.000
20:56397348:T:A	V104D	1.000
20:56397351:C:T	T105I	1.000
20:56397356:C:A	H107N	1.000
20:56397356:C:G	H107D	1.000
20:56397356:C:T	H107Y	1.000
20:56397357:A:G	H107R	1.000
20:56397358:T:A	H107Q	1.000
20:56397358:T:G	H107Q	1.000
20:56397359:A:G	K108E	1.000
20:56397360:A:T	K108I	1.000
20:56397361:A:C	K108N	1.000
20:56397361:A:T	K108N	1.000
20:56397368:T:C	C111R	1.000
20:56397369:G:A	C111Y	1.000
20:56397369:G:T	C111F	1.000
20:56397370:C:G	C111W	1.000
20:56397378:C:A	A114D	1.000
20:56397395:G:A	G120R	1.000
20:56397395:G:C	G120R	1.000
20:56397396:G:A	G120E	1.000
20:56397396:G:T	G120V	1.000
20:56397405:T:A	I123K	1.000
20:56397407:G:C	A124P	1.000
20:56397408:C:A	A124D	1.000
20:56397411:C:T	T125I	1.000
20:56397413:G:A	G126R	1.000

dbSNP variants (sampled 300 via entrez): RS1000195438 (20:56400646 T>C), RS1000209810 (20:56393513 A>G), RS1000331001 (20:56405926 T>A), RS1000407747 (20:56396810 G>A), RS1000638371 (20:56391902 C>T), RS1000827368 (20:56401743 A>G), RS1000880466 (20:56400288 G>A,C), RS1000903261 (20:56402183 T>C), RS1000983748 (20:56395224 T>C), RS1001839929 (20:56399547 T>C), RS1002024153 (20:56404225 G>A), RS1002167883 (20:56404896 A>C), RS1002170745 (20:56403275 C>G,T), RS1002274141 (20:56396442 A>G), RS1002608048 (20:56398243 C>A,G,T)

Disease associations

OMIM: gene MIM:600369 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003901_14	Cognitive decline (age-related)	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects cotreatment, increases expression	1
salinomycin	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Caffeine	decreases phosphorylation	1
Cannabidiol	affects cotreatment, decreases expression	1
Clozapine	decreases expression	1
Coumestrol	increases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Potassium Dichromate	increases expression	1
Quartz	increases expression	1
Ribonucleotides	affects binding	1
Silicon Dioxide	increases expression	1

Clinical trials (associated diseases)

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