CPSF4

Summary

CPSF4 (cleavage and polyadenylation specific factor 4, HGNC:2327) is a protein-coding gene on chromosome 7q22.1, encoding Cleavage and polyadenylation specificity factor subunit 4 (O95639). Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play 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 99.8% of cancer cell lines).

Inhibition of the nuclear export of poly(A)-containing mRNAs caused by the influenza A virus NS1 protein requires its effector domain. The NS1 effector domain functionally interacts with the cellular 30 kDa subunit of cleavage and polyadenylation specific factor 4, an essential component of the 3’ end processing machinery of cellular pre-mRNAs. In influenza virus-infected cells, the NS1 protein is physically associated with cleavage and polyadenylation specific factor 4, 30kD subunit. Binding of the NS1 protein to the 30 kDa protein in vitro prevents CPSF binding to the RNA substrate and inhibits 3’ end cleavage and polyadenylation of host pre-mRNAs. Thus the NS1 protein selectively inhibits the nuclear export of cellular, and not viral, mRNAs. Multiple alternatively spliced transcript variants that encode different isoforms have been described for this gene.

Source: NCBI Gene 10898 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 3 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_006693

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2327
Approved symbol	CPSF4
Name	cleavage and polyadenylation specific factor 4
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	NAR, CPSF30
Ensembl gene	ENSG00000160917
Ensembl biotype	protein_coding
OMIM	603052
Entrez	10898

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 20 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000292476, ENST00000412686, ENST00000430038, ENST00000436336, ENST00000440514, ENST00000441580, ENST00000451876, ENST00000452047, ENST00000465132, ENST00000469897, ENST00000471455, ENST00000482251, ENST00000484112, ENST00000887788, ENST00000887790, ENST00000887791, ENST00000887794, ENST00000887795, ENST00000926770, ENST00000926771, ENST00000967753, ENST00000967754, ENST00000967755, ENST00000967756, ENST00000967757, ENST00000967758

RefSeq mRNA: 5 — MANE Select: NM_006693 NM_001081559, NM_001318160, NM_001318161, NM_001318162, NM_006693

CCDS: CCDS47652, CCDS5664, CCDS83205

Canonical transcript exons

ENST00000292476 — 8 exons

Exon	Start	End
ENSE00001055437	99453966	99454136
ENSE00001842942	99438943	99439185
ENSE00003487558	99452368	99452440
ENSE00003512504	99450276	99450371
ENSE00003549494	99448121	99448273
ENSE00003596374	99444789	99444839
ENSE00003784899	99450702	99450795
ENSE00003848989	99456432	99457373

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 98.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.8118 / max 132.3603, expressed in 1774 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79874	6.8315	1712
79875	2.9803	1054

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.81	gold quality
oocyte	CL:0000023	96.79	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.50	gold quality
mucosa of stomach	UBERON:0001199	96.39	gold quality
cerebellar hemisphere	UBERON:0002245	96.11	gold quality
cerebellar cortex	UBERON:0002129	96.01	gold quality
cerebellum	UBERON:0002037	94.52	gold quality
right frontal lobe	UBERON:0002810	94.21	gold quality
left testis	UBERON:0004533	93.80	gold quality
right testis	UBERON:0004534	93.70	gold quality
nerve	UBERON:0001021	93.65	gold quality
tibial nerve	UBERON:0001323	93.65	gold quality
endothelial cell	CL:0000115	93.23	gold quality
body of pancreas	UBERON:0001150	93.11	gold quality
ectocervix	UBERON:0012249	92.93	gold quality
granulocyte	CL:0000094	92.76	gold quality
type B pancreatic cell	CL:0000169	92.62	gold quality
left uterine tube	UBERON:0001303	92.62	gold quality
skin of leg	UBERON:0001511	92.53	gold quality
body of uterus	UBERON:0009853	92.48	gold quality
skin of abdomen	UBERON:0001416	92.46	gold quality
testis	UBERON:0000473	92.29	gold quality
lower esophagus mucosa	UBERON:0035834	92.27	gold quality
gastrocnemius	UBERON:0001388	92.23	gold quality
adenohypophysis	UBERON:0002196	92.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.20	gold quality
right ovary	UBERON:0002118	91.86	gold quality
cingulate cortex	UBERON:0003027	91.84	gold quality
amygdala	UBERON:0001876	91.80	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting CPSF4, 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-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-607	99.97	73.62	5593
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-5582-5P	99.27	71.42	1879

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 15)

• Data show that the NS1A protein of the pathogenic H5N1 influenza A/Hong Kong/483/97 (HK97) virus isolated from humans has an intrinsic defect in CPSF30 binding. (PMID:17522219)
• CPSF4 plays a critical role in regulating lung cancer cell proliferation and survival and may be a potential prognostic biomarker and therapeutic target for lung adenocarcinoma. (PMID:24358221)
• Data show that 4 drug-like compounds from traditional Chinese Medicine (TCM) database were selected as potential inhibitors for the cleavage and polyadenylation specific factor CPSF30-binding site of influenza A virus of non-structural protein 1 (NS1A). (PMID:24562912)
• CPSF4 upregulates human TERT promoter activity, human TERT expression and telomerase activity. (PMID:24618080)
• unexpectedly found that CPSF subunits CPSF30 and Wdr33 directly contact AAUAAA (PMID:25301780)
• These findings support a role for iron in some zinc-finger proteins. Using electrophoretic mobility shift assays and fluorescence anisotropy, we report that CPSF30 selectively recognizes the AU-rich hexamer (AAUAAA) sequence present in pre-mRNA, providing the first molecular-based evidence to our knowledge for CPSF30/RNA binding. (PMID:27071088)
• Cleavage and polyadenylation specific factor 4 targets NF-kappaB/cyclooxygenase-2 signaling to promote the growth and survival of non-small cell lung carcinoma cells. (PMID:27450326)
• Residues F103 and M106 within the NS1-CPSF4 binding region are important for viral replication. (PMID:28554059)
• 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)
• MiR-4458 inhibits breast cancer cell growth, migration, and invasiveness by targeting CPSF4; results suggest that the miR-4458-CPSF4-COX-2-hTERT axis might serve as a potential target for the treatment of breast cancer patients (PMID:30970220)
• Overproduced CPSF4 Promotes Cell Proliferation and Invasion via PI3K-AKT Signaling Pathway in Oral Squamous Cell Carcinoma. (PMID:33535057)
• CPSF4 promotes triple negative breast cancer metastasis by upregulating MDM4. (PMID:34006850)
• CPSF4 regulates circRNA formation and microRNA mediated gene silencing in hepatocellular carcinoma. (PMID:34103682)
• CPSF4 promotes tumor-initiating phenotype by enhancing VEGF/NRP2/TAZ signaling in lung cancer. (PMID:36567417)
• Cleavage and Polyadenylation-Specific Factor 4 (CPSF4) Expression Is Associated with Enhanced Prostate Cancer Cell Migration and Cell Cycle Dysregulation, In Vitro. (PMID:37629142)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cpsf4	ENSDARG00000020217
mus_musculus	Cpsf4	ENSMUSG00000029625
rattus_norvegicus	Cpsf4	ENSRNOG00000000985
rattus_norvegicus	Cpsf4l2	ENSRNOG00000025217
rattus_norvegicus	Cpsf4-ps1	ENSRNOG00000062241
drosophila_melanogaster	Clp	FBGN0015621

Paralogs (2): ZC3H3 (ENSG00000014164), CPSF4L (ENSG00000187959)

Protein

Protein identifiers

Cleavage and polyadenylation specificity factor subunit 4 — O95639 (reviewed: O95639)

Alternative names: Cleavage and polyadenylation specificity factor 30 kDa subunit, NS1 effector domain-binding protein 1, No arches homolog

All UniProt accessions (7): O95639, B7Z7B0, C9JEV9, C9K0K2, F8WEL7, H7C016, H7C419

UniProt curated annotations — full annotation on UniProt →

Function. Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play 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. CPSF4 binds RNA polymers with a preference for poly(U).

Subunit / interactions. Component of the cleavage and polyadenylation specificity factor (CPSF) complex, composed of CPSF1, CPSF2, CPSF3, CPSF4 and FIP1L1. Interacts with FIP1L1. (Microbial infection) Interacts with influenza A virus NS1 blocks processing of pre-mRNAs, thereby preventing nuclear export of host cell mRNAs.

Subcellular location. Nucleus.

Miscellaneous. May be due to a competing acceptor splice site.

Similarity. Belongs to the CPSF4/YTH1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
O95639-1	1	yes
O95639-2	2
O95639-3	3

RefSeq proteins (5): NP_001075028, NP_001305089, NP_001305090, NP_001305091, NP_006684* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR001878	Znf_CCHC	Domain
IPR036855	Znf_CCCH_sf	Homologous_superfamily
IPR036875	Znf_CCHC_sf	Homologous_superfamily
IPR041686	Znf-CCCH_3	Domain
IPR045348	CPSF4/Yth1	Family

Pfam: PF00098, PF00642, PF15663

UniProt features (32 total): helix 11, zinc finger region 6, strand 5, modified residue 4, splice variant 2, turn 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
7K95	X-RAY DIFFRACTION	1.9
2RHK	X-RAY DIFFRACTION	1.95
7ZYH	X-RAY DIFFRACTION	2.2
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
6DNH	ELECTRON MICROSCOPY	3.4
6URO	ELECTRON MICROSCOPY	3.6
2D9N	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95639-F1	76.60	0.38

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 (4): 212, 267, 200, 202

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-159231	Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-168315	Inhibition of Host mRNA Processing and RNA Silencing
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: 191 (showing top): MORF_MSH3, MORF_BRCA1, MORF_ATRX, AP2_Q3, PUJANA_CHEK2_PCC_NETWORK, MARTINEZ_RB1_TARGETS_DN, MORF_PPP5C, REACTOME_MRNA_3_END_PROCESSING, MORF_FANCG, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_MRNA_3_END_PROCESSING, MORF_RAP1A, DODD_NASOPHARYNGEAL_CARCINOMA_UP, PUJANA_BRCA_CENTERED_NETWORK, MORF_MT4

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

GO Molecular Function (6): RNA binding (GO:0003723), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

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

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Transport of Mature mRNAs Derived from Intronless Transcripts	1
NS1 Mediated Effects on Host Pathways	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
binding	2
RNA processing	1
mRNA metabolic process	1
mRNA processing	1
RNA 3’-end processing	1
nucleic acid binding	1
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
mRNA cleavage factor complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1512 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CPSF4	CPSF1	Q10570	999
CPSF4	CPSF2	Q9P2I0	999
CPSF4	CPSF3	Q9UKF6	997
CPSF4	WDR33	Q9C0J8	997
CPSF4	FIP1L1	Q6UN15	971
CPSF4	CSTF3	Q12996	903
CPSF4	NOC2L	Q9Y3T9	882
CPSF4	CSTF2	P33240	878
CPSF4	CSTF1	Q05048	874
CPSF4	SYMPK	Q92797	856
CPSF4	PCF11	O94913	834
CPSF4	PABPN1	Q86U42	799
CPSF4	CPSF7	Q8N684	796
CPSF4	NUDT21	O43809	787
CPSF4	PAPOLA	P51003	777

IntAct

100 interactions, top by confidence:

A	B	Type	Score
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
CPSF4	FIP1L1	psi-mi:“MI:0914”(association)	0.660
CPSF4	FIP1L1	psi-mi:“MI:0915”(physical association)	0.660
CPSF3	CPSF4	psi-mi:“MI:0914”(association)	0.640
MEOX2	CPSF4	psi-mi:“MI:0915”(physical association)	0.560
	CPSF4	psi-mi:“MI:0915”(physical association)	0.560
CPSF4	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
CPSF4		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
WDR33	CPSF4	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
NS1	CPSF4	psi-mi:“MI:0915”(physical association)	0.500
CDC73	CPSF4	psi-mi:“MI:0914”(association)	0.500
CPSF4	CDC73	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
NPM1	CPSF4	psi-mi:“MI:0914”(association)	0.480
NS1	CPSF4	psi-mi:“MI:0915”(physical association)	0.400
CPSF4	NS	psi-mi:“MI:0915”(physical association)	0.370
NS1	CPSF4	psi-mi:“MI:0915”(physical association)	0.370
CPSF4	NS1	psi-mi:“MI:0915”(physical association)	0.370
NS	CPSF4	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (169): CPSF4 (Affinity Capture-Western), CPSF4 (Two-hybrid), FIP1L1 (Two-hybrid), CPSF4 (Affinity Capture-MS), CPSF4 (Affinity Capture-MS), FIP1L1 (Two-hybrid), CPSF2 (Co-fractionation), CPSF4 (Co-fractionation), CPSF4 (Co-fractionation), CPSF4 (Co-fractionation), WDR33 (Co-fractionation), FIP1L1 (Affinity Capture-Western), CPSF4 (Reconstituted Complex), CPSF4 (Affinity Capture-MS), CPSF4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L1SUL6, A4QJJ7, A4QK16, A6H5F6, A6MM34, A6NH52, A6NMK7, A7M939, A8SEA1, A8W3M5, B0Z4S1, B0Z505, B0Z589, B0Z5H3, B1AR13, B1NWE8, B2LMJ1, O19048, O19137, O95639, P0C7P0, P0DI19, P46292, P60335, P83870, P83871, P98138, Q09G48, Q0G9M1, Q0WMV8, Q15365, Q1KXW1, Q332Y0, Q5E9A3, Q5FVR7, Q5R654, Q63789, Q66KE3, Q68S08, Q6DJP7

Diamond homologs: A6NMK7, A9LNK9, O19137, O95639, Q4P384, Q4WKD9, Q59T36, Q5BGN2, Q5FVR7, Q66KE3, Q6DJP7, Q8BQZ5, Q9VPT8, Q06102, Q2URI6, Q4IPA4, Q6BTT1, Q6C922, Q6CKU1, Q6FTL0, Q758T3, Q7SGR2, Q9UTD1, P0CS64, P0CS65, Q0DA50, Q13064, Q9FE91

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CPSF4	“form complex”	“CPSF complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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	9	71.4×	1e-13
mRNA 3’-end processing	16	43.8×	1e-20
RNA Polymerase II Transcription Termination	14	42.7×	7e-18
Transport of Mature Transcript to Cytoplasm	6	31.7×	1e-06
mRNA Polyadenylation	20	24.4×	1e-20
Transport of Mature mRNA Derived from an Intronless Transcript	6	22.7×	7e-06
mRNA Splicing	10	15.2×	4e-08
Transport of Mature mRNA derived from an Intron-Containing Transcript	7	14.8×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
mRNA 3’-end processing	7	45.2×	4e-08
regulation of alternative mRNA splicing, via spliceosome	6	16.8×	1e-04
mRNA transport	5	15.1×	1e-03
mRNA processing	14	12.7×	2e-09
mRNA splicing, via spliceosome	11	11.6×	4e-07
RNA splicing	10	10.1×	6e-06
chromatin remodeling	7	5.9×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2297 predictions. Top by Δscore:

Variant	Effect	Δscore
7:99439186:G:GG	donor_gain	1.0000
7:99444787:A:AG	acceptor_gain	1.0000
7:99444788:G:GG	acceptor_gain	1.0000
7:99444788:GA:G	acceptor_gain	1.0000
7:99444840:GT:G	donor_loss	1.0000
7:99444841:T:G	donor_loss	1.0000
7:99448115:C:A	acceptor_gain	1.0000
7:99448119:AGGG:A	acceptor_gain	1.0000
7:99448120:GGGG:G	acceptor_gain	1.0000
7:99448269:GTTCG:G	donor_gain	1.0000
7:99450367:GCACG:G	donor_gain	1.0000
7:99450370:CGGT:C	donor_loss	1.0000
7:99450373:T:G	donor_loss	1.0000
7:99450793:GCA:G	donor_gain	1.0000
7:99450796:G:GG	donor_gain	1.0000
7:99452343:A:AG	acceptor_gain	1.0000
7:99452344:T:G	acceptor_gain	1.0000
7:99452351:T:A	acceptor_gain	1.0000
7:99452352:G:A	acceptor_gain	1.0000
7:99452358:T:A	acceptor_gain	1.0000
7:99454136:GGT:G	donor_loss	1.0000
7:99454137:GTG:G	donor_loss	1.0000
7:99439138:TG:T	donor_gain	0.9900
7:99439139:GG:G	donor_gain	0.9900
7:99439181:GGACA:G	donor_gain	0.9900
7:99439182:GACA:G	donor_gain	0.9900
7:99439182:GACAG:G	donor_gain	0.9900
7:99439183:A:T	donor_gain	0.9900
7:99444784:TACAG:T	acceptor_gain	0.9900
7:99444785:A:AG	acceptor_gain	0.9900

AlphaMissense

1793 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:99439134:G:C	A18P	1.000
7:99439152:G:A	G24R	1.000
7:99439152:G:C	G24R	1.000
7:99439153:G:A	G24E	1.000
7:99439170:T:C	F30L	1.000
7:99439171:T:C	F30S	1.000
7:99439171:T:G	F30C	1.000
7:99439172:C:A	F30L	1.000
7:99439172:C:G	F30L	1.000
7:99439180:T:C	M33T	1.000
7:99439180:T:G	M33R	1.000
7:99439181:G:A	M33I	1.000
7:99439181:G:C	M33I	1.000
7:99439181:G:T	M33I	1.000
7:99439182:G:C	D34H	1.000
7:99439183:A:C	D34A	1.000
7:99439183:A:T	D34V	1.000
7:99444790:G:C	K35N	1.000
7:99444790:G:T	K35N	1.000
7:99444804:T:A	V40D	1.000
7:99444806:T:A	C41S	1.000
7:99444806:T:C	C41R	1.000
7:99444807:G:A	C41Y	1.000
7:99444807:G:C	C41S	1.000
7:99444807:G:T	C41F	1.000
7:99444808:T:G	C41W	1.000
7:99444815:T:C	F44L	1.000
7:99444817:T:A	F44L	1.000
7:99444817:T:G	F44L	1.000
7:99444830:T:A	C49S	1.000

dbSNP variants (sampled 300 via entrez): RS1000236639 (7:99440373 CAG>C), RS1000357355 (7:99445716 T>C), RS1000711537 (7:99438279 C>T), RS1000858065 (7:99444334 G>A,T), RS1000889385 (7:99444538 A>G,T), RS1001152144 (7:99449166 G>A), RS1001183304 (7:99449494 G>C), RS1001187819 (7:99438586 C>A,T), RS1001271470 (7:99450644 C>T), RS1001305109 (7:99456671 A>G), RS1001792642 (7:99439965 C>T), RS1001840351 (7:99452694 C>A), RS1002117584 (7:99439598 T>A,G), RS1002180223 (7:99437931 C>T), RS1002211235 (7:99438228 C>T)

Disease associations

OMIM: gene MIM:603052 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004730_2	Facial emotion recognition (sad faces)	3.000000e-06
GCST005144_1	Tacrolimus trough concentration in kidney transplant patients	2.000000e-17
GCST005335_2	Diffuse cutaneous systemic sclerosis	2.000000e-06
GCST006249_21	Serum metabolite levels	4.000000e-11
GCST006249_45	Serum metabolite levels	6.000000e-32
GCST006249_47	Serum metabolite levels	1.000000e-45
GCST90002389_160	Lymphocyte percentage of white cells	4.000000e-16
GCST90002399_184	Neutrophil percentage of white cells	2.000000e-15

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008329	facial emotion recognition measurement
EFO:0008458	tacrolimus measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066178 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
beta-methylcholine	affects expression	1
K 7174	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
pyrimidifen	decreases expression	1
thifluzamide	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	increases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697614	Binding	Inhibition of CPSF4 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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