CPSF1

Summary

CPSF1 (cleavage and polyadenylation specific factor 1, HGNC:2324) is a protein-coding gene on chromosome 8q24.3, encoding Cleavage and polyadenylation specificity factor subunit 1 (Q10570). Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3’-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. It is a common-essential gene (DepMap: required in 98.8% of cancer cell lines).

Cleavage and polyadenylation specificity factor (CPSF) is a multisubunit complex that plays a central role in 3-prime processing of pre-mRNAs. CPSF recognizes the AAUAAA signal in the pre-mRNA and interacts with other proteins to facilitate both RNA cleavage and poly(A) synthesis. CPSF1 is the largest subunit of the CPSF complex (Murthy and Manley, 1995 [PubMed 7590244]).

Source: NCBI Gene 29894 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myopia 27 (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 318 total — 5 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 3
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_013291

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2324
Approved symbol	CPSF1
Name	cleavage and polyadenylation specific factor 1
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	CPSF160
Ensembl gene	ENSG00000071894
Ensembl biotype	protein_coding
OMIM	606027
Entrez	29894

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 21 protein_coding, 9 retained_intron, 1 nonsense_mediated_decay

ENST00000526271, ENST00000527827, ENST00000527916, ENST00000529288, ENST00000531042, ENST00000531480, ENST00000531727, ENST00000532560, ENST00000532725, ENST00000532935, ENST00000533492, ENST00000616140, ENST00000620219, ENST00000622776, ENST00000886809, ENST00000886810, ENST00000886811, ENST00000886812, ENST00000886813, ENST00000886814, ENST00000886815, ENST00000886816, ENST00000886817, ENST00000886818, ENST00000886819, ENST00000913993, ENST00000913994, ENST00000913995, ENST00000913996, ENST00000913997, ENST00000913998

RefSeq mRNA: 1 — MANE Select: NM_013291 NM_013291

CCDS: CCDS34966

Canonical transcript exons

ENST00000616140 — 38 exons

Exon	Start	End
ENSE00003482940	144401211	144401291
ENSE00003614369	144401430	144401563
ENSE00003712245	144398779	144398868
ENSE00003713910	144400354	144400493
ENSE00003716011	144400671	144400817
ENSE00003717346	144394234	144394300
ENSE00003718378	144400924	144401075
ENSE00003718996	144409015	144409172
ENSE00003720349	144398958	144399038
ENSE00003725856	144409289	144409335
ENSE00003727674	144399992	144400085
ENSE00003738057	144394113	144394160
ENSE00003744072	144393452	144393590
ENSE00003744148	144393231	144393365
ENSE00003748479	144393667	144393796
ENSE00003788623	144393883	144394038
ENSE00003889080	144395098	144395182
ENSE00003889229	144398525	144398638
ENSE00003889326	144399781	144399868
ENSE00003889354	144397954	144398132
ENSE00003889632	144395265	144395355
ENSE00003889855	144396348	144396500
ENSE00003890292	144397743	144397879
ENSE00003890322	144394882	144395023
ENSE00003890453	144401646	144401673
ENSE00003890597	144397207	144397413
ENSE00003890813	144396598	144396741
ENSE00003890831	144399276	144399373
ENSE00003891118	144396840	144396929
ENSE00003891484	144399128	144399202
ENSE00003892421	144395435	144395551
ENSE00003893798	144399452	144399503
ENSE00003893840	144394379	144394555
ENSE00003894660	144398302	144398443
ENSE00003894668	144399588	144399710
ENSE00003895112	144397487	144397661
ENSE00003895529	144400166	144400276
ENSE00003895575	144394644	144394796

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.1606 / max 162.1670, expressed in 1805 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95664	24.1346	1803
95665	5.0429	1540
95663	0.7342	448
95666	0.2036	102
95660	0.0217	7
95662	0.0203	9
95661	0.0034	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	98.97	gold quality
left testis	UBERON:0004533	98.90	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.51	gold quality
right uterine tube	UBERON:0001302	98.49	gold quality
cerebellar hemisphere	UBERON:0002245	98.38	gold quality
cerebellum	UBERON:0002037	98.36	gold quality
cerebellar cortex	UBERON:0002129	98.36	gold quality
granulocyte	CL:0000094	98.35	gold quality
pituitary gland	UBERON:0000007	98.07	gold quality
lower esophagus mucosa	UBERON:0035834	98.00	gold quality
adenohypophysis	UBERON:0002196	97.99	gold quality
duodenum	UBERON:0002114	97.92	gold quality
testis	UBERON:0000473	97.82	gold quality
mucosa of transverse colon	UBERON:0004991	97.79	gold quality
spleen	UBERON:0002106	97.77	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.75	gold quality
small intestine	UBERON:0002108	97.51	gold quality
right ovary	UBERON:0002118	97.44	gold quality
body of pancreas	UBERON:0001150	97.35	gold quality
right lobe of thyroid gland	UBERON:0001119	97.31	gold quality
metanephros cortex	UBERON:0010533	97.31	gold quality
body of stomach	UBERON:0001161	97.29	gold quality
prostate gland	UBERON:0002367	97.26	gold quality
transverse colon	UBERON:0001157	97.11	gold quality
primary visual cortex	UBERON:0002436	97.08	gold quality
left lobe of thyroid gland	UBERON:0001120	97.00	gold quality
left ovary	UBERON:0002119	96.98	gold quality
apex of heart	UBERON:0002098	96.91	gold quality
body of uterus	UBERON:0009853	96.88	gold quality
tibial nerve	UBERON:0001323	96.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.85
E-GEOD-110499	no	51.92

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 6)

• CPSF1 was identified among protein-binding candidates. A consensus polyadenylation signal AAUAAA is present in intron 6 of IL7 receptor directly downstream from the 5’ splice site. Mutations to this site and CPSF1 knockdown increased exon 6 inclusion. (PMID:23151878)
• The authors define the molecular architecture of the core human CPSF complex comprising CPSF160, WDR33, CPSF30 and Fip1 and identify specific domains involved in inter-subunit interactions. Together, these results shed light on the function of CPSF in mediating polyA signal-dependent RNA cleavage and polyadenylation. (PMID:29274231)
• Knockdown of CPSF inhibits the proliferation, migration and invasion of ovarian carcinoma cells. (PMID:29358555)
• cryo-electron microscopic analysis of a core CPSF module bound to the polyadenylation signal hexamer motif (PMID:29358758)
• Heterozygous loss-of-function mutations in CPSF1 are associated with early-onset high myopia and that CPSF1 may play an important role in the development of retinal ganglion cell axon projection. (PMID:30689892)
• Epidermal progenitors suppress GRHL3-mediated differentiation through intronic polyadenylation promoted by CPSF-HNRNPA3 collaboration. (PMID:33469008)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpsf1	ENSDARG00000034178
mus_musculus	Cpsf1	ENSMUSG00000034022
rattus_norvegicus	Cpsf1	ENSRNOG00000030705
drosophila_melanogaster	Cpsf160	FBGN0024698
caenorhabditis_elegans		WBGENE00022301

Paralogs (2): DDB1 (ENSG00000167986), SF3B3 (ENSG00000189091)

Protein

Protein identifiers

Cleavage and polyadenylation specificity factor subunit 1 — Q10570 (reviewed: Q10570)

Alternative names: Cleavage and polyadenylation specificity factor 160 kDa subunit

All UniProt accessions (4): Q10570, A0A087WTV4, A0A087X101, E9PIM1

UniProt curated annotations — full annotation on UniProt →

Function. Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3’-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. This subunit is involved in the RNA recognition step of the polyadenylation reaction. May play a role in eye morphogenesis and the development of retinal ganglion cell projections to the midbrain.

Subunit / interactions. Component of the cleavage and polyadenylation specificity factor (CPSF) complex, composed of CPSF1, CPSF2, CPSF3, CPSF4 and FIP1L1. Found in a complex with CPSF1, FIP1L1 and PAPOLA. Interacts with FIP1L1, TENT2/GLD2 and SRRM1. Interacts with TUT1; the interaction is direct and mediates the recruitment of the CPSF complex on the 3’UTR of selected pre-mRNAs.

Subcellular location. Nucleus. Nucleoplasm.

Tissue specificity. Widely expressed, with high expression in the retina.

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

Disease relevance. Myopia 27, autosomal dominant (MYP27) [MIM:618827] A form of myopia, a refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far. MYP27 patients are affected by early-onset high myopia with increased axial lengths. Fundus changes include optic nerve head crescent and tigroid appearance of the posterior retina. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CPSF1 family.

RefSeq proteins (1): NP_037423* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004871	RSE1/DDB1/CPSF1_C	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR018846	Beta-prop_RSE1/DDB1/CPSF1_1st	Domain
IPR050358	RSE1/DDB1/CFT1	Family
IPR058543	Beta-prop_RSE1/DDB1/CPSF1_2nd	Domain

Pfam: PF03178, PF10433, PF23726

UniProt features (146 total): strand 103, turn 14, helix 14, region of interest 4, sequence variant 3, sequence conflict 2, compositionally biased region 2, modified residue 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
9T3X	ELECTRON MICROSCOPY	2.1
6F9N	X-RAY DIFFRACTION	2.5
8E3I	ELECTRON MICROSCOPY	2.53
9OXE	ELECTRON MICROSCOPY	2.53
8E3Q	ELECTRON MICROSCOPY	2.68
8R8R	ELECTRON MICROSCOPY	2.79
6URG	ELECTRON MICROSCOPY	3
6FUW	ELECTRON MICROSCOPY	3.07
9OXS	ELECTRON MICROSCOPY	3.07
6BLY	ELECTRON MICROSCOPY	3.36
6DNH	ELECTRON MICROSCOPY	3.4
6URO	ELECTRON MICROSCOPY	3.6
6BM0	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q10570-F1	82.97	0.62

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): 756, 766

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-159231	Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-6784531	tRNA processing in the nucleus
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: 133 (showing top): WANG_CLIM2_TARGETS_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, BROWNE_HCMV_INFECTION_48HR_DN, ONKEN_UVEAL_MELANOMA_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_MRNA_3_END_PROCESSING, BROWNE_HCMV_INFECTION_14HR_DN, LIAO_METASTASIS, DANG_BOUND_BY_MYC, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, SHEN_SMARCA2_TARGETS_DN, REACTOME_METABOLISM_OF_RNA, PARENT_MTOR_SIGNALING_UP

GO Biological Process (3): mRNA processing (GO:0006397), co-transcriptional RNA 3’-end processing, cleavage and polyadenylation pathway (GO:0180012), RNA 3’-end processing (GO:0031123)

GO Molecular Function (5): enzyme binding (GO:0019899), mRNA 3’-UTR AU-rich region binding (GO:0035925), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), mRNA cleavage and polyadenylation specificity factor complex (GO:0005847)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Transport of Mature mRNAs Derived from Intronless Transcripts	1
tRNA processing	1
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
RNA processing	2
binding	2
mRNA metabolic process	1
RNA 3’-end processing	1
protein binding	1
mRNA 3’-UTR binding	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
mRNA cleavage factor complex	1

Protein interactions and networks

STRING

2282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPSF1	CPSF4	O95639	999
CPSF1	CPSF2	Q9P2I0	999
CPSF1	CPSF3	Q9UKF6	998
CPSF1	CSTF3	Q12996	998
CPSF1	WDR33	Q9C0J8	998
CPSF1	FIP1L1	Q6UN15	993
CPSF1	PAPOLA	P51003	968
CPSF1	SYMPK	Q92797	961
CPSF1	CSTF1	Q05048	919
CPSF1	CSTF2	P33240	919
CPSF1	CPSF7	Q8N684	894
CPSF1	NUDT21	O43809	859
CPSF1	PAPOLG	Q9BWT3	828
CPSF1	PAPOLB	Q9NRJ5	818
CPSF1	CPSF6	Q16630	803

IntAct

132 interactions, top by confidence:

A	B	Type	Score
CPSF1	CPSF4	psi-mi:“MI:0915”(physical association)	0.670
CPSF3	CPSF4	psi-mi:“MI:0914”(association)	0.640
CDC73	CSTF2	psi-mi:“MI:0914”(association)	0.580
CDC73	CSTF2	psi-mi:“MI:0915”(physical association)	0.580
CPSF1	REL	psi-mi:“MI:0915”(physical association)	0.560
NS1	PIK3R2	psi-mi:“MI:0914”(association)	0.560
CPSF1	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
INCA1	CPSF1	psi-mi:“MI:0915”(physical association)	0.560
CPSF1	CPSF4	psi-mi:“MI:0915”(physical association)	0.560
SYMPK	CPSF4	psi-mi:“MI:0914”(association)	0.530
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
WDR33	CPSF4	psi-mi:“MI:0914”(association)	0.530
NS1	PIK3R2	psi-mi:“MI:0914”(association)	0.530
CDC73	CPSF4	psi-mi:“MI:0914”(association)	0.500
CPSF1	NPM1	psi-mi:“MI:0915”(physical association)	0.500
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
TUT1	CPSF1	psi-mi:“MI:0914”(association)	0.460
RPP38	CPSF1	psi-mi:“MI:0915”(physical association)	0.400
CPSF1	WWOX	psi-mi:“MI:0915”(physical association)	0.400
ECE1	CPSF1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (357): CPSF1 (Affinity Capture-Western), CPSF1 (Two-hybrid), CPSF1 (Affinity Capture-RNA), CPSF1 (Affinity Capture-RNA), CPSF1 (Affinity Capture-MS), CPSF1 (Affinity Capture-MS), CPSF1 (Affinity Capture-MS), CPSF1 (Affinity Capture-MS), CPSF1 (Affinity Capture-MS), CPSF1 (Co-fractionation), CPSF1 (Co-fractionation), CPSF2 (Co-fractionation), CPSF3 (Co-fractionation), CPSF4 (Co-fractionation), CSTF2 (Co-fractionation)

ESM2 similar proteins: A0A0R4IC37, A1A4K3, A2CEI4, B1WC10, E9PY46, F1QEB7, F4IDS7, O08658, O13046, O75694, O75717, O95876, P33194, P37199, P59328, Q08D69, Q10569, Q10570, Q16531, Q32NR9, Q3U1J4, Q4ADV7, Q566H4, Q5DQR4, Q5R649, Q5U1Z0, Q5ZLG9, Q6P6Z0, Q6PGF3, Q6PJI9, Q7XWP1, Q802U2, Q805F9, Q8BMG7, Q8C0M0, Q8C456, Q8CEC0, Q8CJF7, Q8K1X1, Q8NFP9

Diamond homologs: A0A0R4IC37, A8XPU7, Q10569, Q10570, Q7XWP1, Q9EPU4, Q9FGR0, Q9N4C2, Q9V726, Q4WLI5, Q5B1X8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CPSF1	“form complex”	“CPSF complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 120 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	8	53.7×	1e-10
RNA Polymerase II Transcription Termination	10	25.8×	4e-10
mRNA 3’-end processing	11	25.5×	6e-11
mRNA Polyadenylation	20	20.7×	1e-18
Transport of Mature mRNA Derived from an Intronless Transcript	6	19.2×	4e-05
Processing of Capped Intron-Containing Pre-mRNA	13	12.6×	2e-09
mRNA Splicing	8	10.3×	5e-05
Dengue Virus-Host Interactions	18	9.7×	6e-11

GO biological processes:

GO term	Partners	Fold	FDR
mRNA 3’-end processing	7	36.4×	5e-07
regulation of alternative mRNA splicing, via spliceosome	5	11.3×	8e-03
mRNA splicing, via spliceosome	11	9.3×	7e-06
mRNA processing	11	8.0×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	3
Uncertain significance	233
Likely benign	18
Benign	1

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1074846	NM_013291.3(CPSF1):c.2524dup (p.Glu842fs)	Pathogenic
829510	NM_013291.3(CPSF1):c.4146-2A>G	Pathogenic
829512	NM_013291.3(CPSF1):c.3823G>T (p.Asp1275Tyr)	Pathogenic
829514	NM_013291.3(CPSF1):c.1858C>T (p.Gln620Ter)	Pathogenic
837526	NM_013291.3(CPSF1):c.1603_1604del (p.Met535fs)	Pathogenic
3068158	NM_013291.3(CPSF1):c.539+1G>A	Likely pathogenic
3235178	NM_013291.3(CPSF1):c.1258_1259del (p.Lys420fs)	Likely pathogenic
4293872	NM_013291.3(CPSF1):c.2156del (p.Asp719fs)	Likely pathogenic

SpliceAI

5358 predictions. Top by Δscore:

Variant	Effect	Δscore
8:144393450:A:AC	donor_gain	1.0000
8:144393451:C:CC	donor_gain	1.0000
8:144393451:CT:C	donor_gain	1.0000
8:144393451:CTA:C	donor_gain	1.0000
8:144393451:CTAT:C	donor_gain	1.0000
8:144393451:CTATG:C	donor_gain	1.0000
8:144393587:CATC:C	acceptor_gain	1.0000
8:144393589:TC:T	acceptor_gain	1.0000
8:144393590:CC:C	acceptor_gain	1.0000
8:144393590:CCTGG:C	acceptor_loss	1.0000
8:144393591:C:CC	acceptor_gain	1.0000
8:144393591:CT:C	acceptor_loss	1.0000
8:144393592:T:A	acceptor_loss	1.0000
8:144393661:GCTC:G	donor_loss	1.0000
8:144393662:CTCA:C	donor_loss	1.0000
8:144393663:TCA:T	donor_loss	1.0000
8:144393664:CACCG:C	donor_loss	1.0000
8:144393666:C:CT	donor_loss	1.0000
8:144393792:GGTGG:G	acceptor_gain	1.0000
8:144393793:GTGG:G	acceptor_gain	1.0000
8:144393794:TGG:T	acceptor_gain	1.0000
8:144393795:GG:G	acceptor_gain	1.0000
8:144393796:GC:G	acceptor_loss	1.0000
8:144393797:C:CA	acceptor_loss	1.0000
8:144393797:C:CC	acceptor_gain	1.0000
8:144393801:C:CT	acceptor_gain	1.0000
8:144393802:A:T	acceptor_gain	1.0000
8:144393806:G:C	acceptor_gain	1.0000
8:144393806:G:GC	acceptor_gain	1.0000
8:144394039:C:CC	acceptor_gain	1.0000

AlphaMissense

9421 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:144393468:C:T	G1423D	1.000
8:144393480:G:T	A1419D	1.000
8:144393715:A:G	L1366P	1.000
8:144393727:A:G	L1362P	1.000
8:144393736:A:G	L1359P	1.000
8:144394011:A:G	L1296P	1.000
8:144394028:A:C	S1290R	1.000
8:144394028:A:T	S1290R	1.000
8:144394030:T:G	S1290R	1.000
8:144394422:A:G	L1234P	1.000
8:144394446:T:A	D1226V	1.000
8:144394503:T:A	D1207V	1.000
8:144394503:T:C	D1207G	1.000
8:144394504:C:G	D1207H	1.000
8:144394508:G:C	F1205L	1.000
8:144394508:G:T	F1205L	1.000
8:144394509:A:C	F1205C	1.000
8:144394509:A:G	F1205S	1.000
8:144394510:A:G	F1205L	1.000
8:144394510:A:T	F1205I	1.000
8:144394651:C:T	G1187D	1.000
8:144394886:C:T	G1137E	1.000
8:144394887:C:G	G1137R	1.000
8:144394887:C:T	G1137R	1.000
8:144394926:C:A	G1124W	1.000
8:144395120:A:G	W1084R	1.000
8:144395120:A:T	W1084R	1.000
8:144395534:A:C	S999R	1.000
8:144395534:A:T	S999R	1.000
8:144395536:T:G	S999R	1.000

dbSNP variants (sampled 300 via entrez): RS1000004491 (8:144410450 T>A), RS1000079849 (8:144400198 C>G,T), RS1000327769 (8:144402263 G>A), RS1001277393 (8:144405090 T>G), RS1001364441 (8:144393113 T>C), RS1001460151 (8:144400042 G>A), RS1002563980 (8:144408891 C>A), RS1002674087 (8:144406210 G>T), RS1002854810 (8:144400890 C>G,T), RS1003237699 (8:144411153 G>T), RS1003544905 (8:144401132 T>C), RS1003673112 (8:144404831 C>A,T), RS1003835135 (8:144409872 A>G), RS1004352058 (8:144407424 G>A), RS1004581928 (8:144401726 T>C)

Disease associations

OMIM: gene MIM:606027 | disease phenotypes: MIM:618827

GenCC curated gene-disease

Disease	Classification	Inheritance
myopia 27	Strong	Autosomal dominant

Mondo (1): myopia 27 (MONDO:0032941)

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0007800	Increased axial length of the globe
HP:0011003	High myopia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002598_30	Educational attainment	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724781 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.01	Kd	9.747	nM	CHEMBL3752910
7.93	ED50	11.83	nM	CHEMBL3752910
5.81	IC50	1540	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 8 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149844: Binding affinity to human CPSF1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0097	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178616: Inhibition of CPSF1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	1.5400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
FR900359	affects phosphorylation	1
bisphenol A	decreases expression	1
potassium perchlorate	decreases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	increases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, increases expression	1
bathocuproine sulfonate	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
ICG 001	increases expression	1
MT19c compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Cannabidiol	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Methotrexate	affects response to substance	1
Piroxicam	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Rotenone	increases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Vitamin E	increases expression	1
beta-Naphthoflavone	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652886	Binding	Binding affinity to human CPSF1 incubated for 45 mins by Kinobead based pull down assay	NVP-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.