CSTF2

Summary

CSTF2 (cleavage stimulation factor subunit 2, HGNC:2484) is a protein-coding gene on chromosome Xq22.1, encoding Cleavage stimulation factor subunit 2 (P33240). One of the multiple factors required for polyadenylation and 3’-end cleavage of mammalian pre-mRNAs.

This gene encodes a nuclear protein with an RRM (RNA recognition motif) domain. The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3’ end cleavage and polyadenylation of pre-mRNAs. Specifically, this protein binds GU-rich elements within the 3’-untranslated region of mRNAs.

Source: NCBI Gene 1478 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder, X-linked 113 (Limited, GenCC)
• Clinical variants (ClinVar): 119 total — 3 pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_001325

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2484
Approved symbol	CSTF2
Name	cleavage stimulation factor subunit 2
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	CstF-64
Ensembl gene	ENSG00000101811
Ensembl biotype	protein_coding
OMIM	300907
Entrez	1478

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 nonsense_mediated_decay

ENST00000372972, ENST00000413437, ENST00000415585, ENST00000475126, ENST00000866722, ENST00000866723, ENST00000866724, ENST00000924424, ENST00000924425, ENST00000924426, ENST00000948100, ENST00000948101

RefSeq mRNA: 3 — MANE Select: NM_001325 NM_001306206, NM_001306209, NM_001325

CCDS: CCDS14473, CCDS78498

Canonical transcript exons

ENST00000372972 — 14 exons

Exon	Start	End
ENSE00000673632	100822251	100822420
ENSE00000673635	100823292	100823428
ENSE00000673638	100823886	100824005
ENSE00000673657	100833180	100833472
ENSE00001797690	100820391	100820474
ENSE00001943170	100840714	100841520
ENSE00003482279	100837339	100837449
ENSE00003559745	100821527	100821605
ENSE00003604446	100831515	100831656
ENSE00003641637	100838239	100838364
ENSE00003646086	100828040	100828102
ENSE00003664785	100832734	100832909
ENSE00003693529	100826634	100826757
ENSE00003788551	100824120	100824257

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 95.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.3231 / max 224.4737, expressed in 1802 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196938	19.3231	1802

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.95	gold quality
secondary oocyte	CL:0000655	94.96	gold quality
oral cavity	UBERON:0000167	86.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.30	gold quality
palpebral conjunctiva	UBERON:0001812	85.83	gold quality
pharyngeal mucosa	UBERON:0000355	85.73	gold quality
esophagus squamous epithelium	UBERON:0006920	85.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.62	gold quality
epithelium of esophagus	UBERON:0001976	85.45	gold quality
esophagus mucosa	UBERON:0002469	85.44	gold quality
ganglionic eminence	UBERON:0004023	84.38	gold quality
buccal mucosa cell	CL:0002336	84.37	silver quality
epithelium of nasopharynx	UBERON:0001951	84.21	gold quality
ventricular zone	UBERON:0003053	84.20	gold quality
squamous epithelium	UBERON:0006914	84.17	gold quality
mucosa of transverse colon	UBERON:0004991	83.39	gold quality
rectum	UBERON:0001052	83.25	gold quality
cervix squamous epithelium	UBERON:0006922	83.15	gold quality
lower esophagus mucosa	UBERON:0035834	82.63	gold quality
tonsil	UBERON:0002372	82.37	gold quality
embryo	UBERON:0000922	82.24	gold quality
olfactory bulb	UBERON:0002264	82.04	gold quality
colonic mucosa	UBERON:0000317	81.84	gold quality
stromal cell of endometrium	CL:0002255	81.66	gold quality
mucosa of sigmoid colon	UBERON:0004993	81.56	gold quality
gingival epithelium	UBERON:0001949	81.30	silver quality
male germ cell	CL:0000015	80.97	silver quality
type B pancreatic cell	CL:0000169	80.91	gold quality
gingiva	UBERON:0001828	80.87	gold quality
sperm	CL:0000019	80.66	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting CSTF2, 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-3662	99.99	73.82	5684
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-5006-5P	98.79	66.92	1246

Literature-anchored findings (GeneRIF, showing 21)

• dynamics of the CstF-64 RNA-binding domain, both free and bound to two GU-rich RNA sequences that represent polyadenylation regulatory elements, by NMR Spectroscopy (PMID:15769465)
• CstF64 (cstf2) and not other CstF subunits induced by lipopolysaccharide (LPS) in murine macrophages and changes polyA site use (PMID:16207706)
• The inactivity of the RSV poly(A) site was at least in part due to poor CstF binding since tethering CstF to the RSV substrate activated polyadenylation. (PMID:18272196)
• The Hinge domain is necessary for CstF-64 interaction with CstF-77 and consequent nuclear localization. (PMID:19887456)
• nuclear accumulation of CstF-64 depends on binding to CstF-77 not symplekin; interaction between CstF-64/CstF-64Tau and CstF-77 are important for maintenance of nuclear levels of CstF complex components and intracellular localization, stability, function (PMID:21119002)
• CSTF2 is likely to play an important role in lung carcinogenesis and be a prognostic biomarker in the clinic. (PMID:21813631)
• CstF64 binds to thousands of dormant intronic PASs that are suppressed, at least in part, by U1 small nuclear ribonucleoproteins (PMID:23112178)
• CstF64 and CstF64tau modulate one another’s expression and play overlapping as well as distinct roles in regulating global alternative polyadenylation profiles. (PMID:24149845)
• CstF64 is central to the function of a heat-labile factor, composed of cleavage/polyadenylation specificity factor, symplekin, and cleavage stimulation factor 64 and appears to be at least partly responsible for its cell cycle regulation. (PMID:25266659)
• CstF64, an essential polyadenylation factor, is a master regulator of 3’-UTR shortening across multiple tumour types. (PMID:25409906)
• CstF-64 is dispensable for the expression/3’-end processing of Star-PAP target mRNAs.CstF-64 and 3’-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding poly A polymerase. (PMID:26496945)
• hnRNP H binds to two specific G-runs in exon 5a of ACHE and activates the distal alternative 3 splice site (ss) between exons 5a and 5b. Furthermore, hnRNP H competes for binding of CstF64 to the overlapping binding sites in exon 5a, and suppresses the selection of a cryptic polyadenylation site, which additionally ensures transcription of the distal 3 ss required for the generation of AChET isoform. (PMID:28180311)
• The findings demonstrate that constitutive Tip110 expression in human cord blood CD34(+) cells is regulated, at least in part, through its interaction with CstF64, recruitment of CstF64 to, and selective usage of two polyadenylation sites within its 3’UTR. (PMID:29583087)
• CSTF2 exerts critical roles in activation of RAC1 by promoting 3’UTR shortening of RAC1 mRNAs through two transcription elongation factors, AFF1 and AFF4, in urothelial carcinoma of the bladder pathogenesis (PMID:30143523)
• Reverse genetics and nuclear magnetic resonance studies of recombinant CstF-64 (RRM-Hinge) and CstF-77 (monkeytail-carboxy-terminal domain) indicate that the last 30 amino acids of CstF-77 increases the stability of the RRM, thus altering the affinity of the complex for RNA. These results provide new insights into the mechanism by which CstF regulates the location of the RNA cleavage site during Cleavage/polyadenylation. (PMID:30257008)
• A missense mutation in the CSTF2 gene that impairs the function of the RNA recognition motif and causes defects in 3’ end processing is associated with intellectual disability in humans. (PMID:32816001)
• CstF64-Induced Shortening of the BID 3’UTR Promotes Esophageal Squamous Cell Carcinoma Progression by Disrupting ceRNA Cross-talk with ZFP36L2. (PMID:34607841)
• Cleavage stimulation factor 2 promotes malignant progression of liver hepatocellular carcinoma by activating phosphatidylinositol 3’-kinase/protein kinase B/mammalian target of rapamycin pathway. (PMID:35412944)
• Alternative polyadenylation writer CSTF2 forms a positive loop with FGF2 to promote tubular epithelial-mesenchymal transition and renal fibrosis. (PMID:36113752)
• CSTF2 mediated mRNA N[6]-methyladenosine modification drives pancreatic ductal adenocarcinoma m[6]A subtypes. (PMID:37816727)
• Describes the induction of CSTF2 in the growth phase of cells. (PMID:9736695)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cstf2	ENSDARG00000090788
mus_musculus	Cstf2	ENSMUSG00000031256
rattus_norvegicus	Cstf2	ENSRNOG00000048025
drosophila_melanogaster	CstF64	FBGN0027841
caenorhabditis_elegans		WBGENE00000774
caenorhabditis_elegans	R06C1.4	WBGENE00011059

Paralogs (5): U2AF2 (ENSG00000063244), RBMX2 (ENSG00000134597), ZCRB1 (ENSG00000139168), UHMK1 (ENSG00000152332), CSTF2T (ENSG00000177613)

Protein

Protein identifiers

Cleavage stimulation factor subunit 2 — P33240 (reviewed: P33240)

Alternative names: CF-1 64 kDa subunit, Cleavage stimulation factor 64 kDa subunit

All UniProt accessions (4): P33240, A0A0A0MT56, E7EWR4, E9PID8

UniProt curated annotations — full annotation on UniProt →

Function. One of the multiple factors required for polyadenylation and 3’-end cleavage of mammalian pre-mRNAs. This subunit is directly involved in the binding to pre-mRNAs.

Subunit / interactions. The CSTF complex is composed of CSTF1 (50 kDa subunit), CSTF2 (64 kDa subunit) and CSTF3 (77 kDa subunit). CSTF2 directly interacts with CSTF3, SYMPK and RPO2TC1. Interacts with HSF1 in heat-stressed cells. Interacts with CPSF2, CPSF3 and FIP1L1. Interacts with DDX1.

Subcellular location. Nucleus.

Disease relevance. Intellectual developmental disorder, X-linked 113 (XLID113) [MIM:301116] A disorder characterized by mild intellectual disability, and developmental delay mainly affecting verbal and non-verbal communication skills. Motor development is normal. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated during the G0 to S phase transition.

Isoforms (2)

UniProt ID	Names	Canonical?
P33240-1	1	yes
P33240-2	2

RefSeq proteins (3): NP_001293135, NP_001293138, NP_001316* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR025742	CSTF2_hinge	Domain
IPR026896	CSTF_C	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR038192	CSTF_C_sf	Homologous_superfamily

Pfam: PF00076, PF14304, PF14327

UniProt features (48 total): repeat 12, helix 9, strand 7, region of interest 6, modified residue 6, compositionally biased region 2, chain 1, domain 1, cross-link 1, splice variant 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1P1T	SOLUTION NMR
2J8P	SOLUTION NMR
6Q2I	SOLUTION NMR
6TZE	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P33240-F1	60.94	0.12

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 (7): 14, 308, 468, 475, 518, 524, 189

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
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: 187 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_RESPONSE_TO_NERVE_GROWTH_FACTOR, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, 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, GARY_CD5_TARGETS_DN, WANG_CISPLATIN_RESPONSE_AND_XPC_DN, GOBP_RESPONSE_TO_GROWTH_FACTOR, GOBP_HISTONE_MRNA_METABOLIC_PROCESS, ZHAN_EARLY_DIFFERENTIATION_GENES_DN

GO Biological Process (3): mRNA 3’-end processing (GO:0031124), cellular response to nerve growth factor stimulus (GO:1990090), mRNA processing (GO:0006397)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), mRNA cleavage and polyadenylation specificity factor complex (GO:0005847), nuclear body (GO:0016604), cleavage body (GO:0071920)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
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
mRNA processing	1
RNA 3’-end processing	1
cellular response to growth factor stimulus	1
response to nerve growth factor	1
RNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
mRNA cleavage factor complex	1
nucleoplasm	1
intracellular membraneless organelle	1
nuclear body	1

Protein interactions and networks

STRING

3160 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSTF2	CSTF1	Q05048	999
CSTF2	CSTF3	Q12996	999
CSTF2	SYMPK	Q92797	997
CSTF2	CPSF2	Q9P2I0	978
CSTF2	CPSF3	Q9UKF6	974
CSTF2	CPSF1	Q10570	919
CSTF2	PCF11	O94913	910
CSTF2	WDR33	Q9C0J8	899
CSTF2	LMOD1	P29536	891
CSTF2	CPSF4	O95639	878
CSTF2	CPSF6	Q16630	839
CSTF2	LSM11	P83369	828
CSTF2	CPSF7	Q8N684	810
CSTF2	NUDT21	O43809	807
CSTF2	PAPOLA	P51003	802
CSTF2	PAPOLG	Q9BWT3	802

IntAct

191 interactions, top by confidence:

A	B	Type	Score
UBQLN1	CSTF2	psi-mi:“MI:0915”(physical association)	0.780
CSTF2	UBQLN1	psi-mi:“MI:0915”(physical association)	0.780
HGS	CSTF2	psi-mi:“MI:0915”(physical association)	0.720
TFG	CSTF2	psi-mi:“MI:0915”(physical association)	0.720
CSTF2	HGS	psi-mi:“MI:0915”(physical association)	0.720
CSTF2	TFG	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
BARD1	CSTF2	psi-mi:“MI:0915”(physical association)	0.700
CSTF2	BARD1	psi-mi:“MI:0915”(physical association)	0.700
BARD1	CSTF2	psi-mi:“MI:0914”(association)	0.700
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
BARD1	PARN	psi-mi:“MI:0914”(association)	0.580
SS18L1	CSTF2	psi-mi:“MI:0915”(physical association)	0.560
CSTF2	SPAG8	psi-mi:“MI:0915”(physical association)	0.560
CSTF2	ZNF341	psi-mi:“MI:0915”(physical association)	0.560
CSTF2	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (245): CSTF2 (Affinity Capture-Western), HGS (Two-hybrid), TFG (Two-hybrid), SS18L1 (Two-hybrid), SPAG8 (Two-hybrid), UBQLN1 (Two-hybrid), ZNF341 (Two-hybrid), CSTF2 (Affinity Capture-RNA), CSTF2 (Affinity Capture-MS), CSTF2 (Affinity Capture-MS), CSTF2 (Affinity Capture-MS), CSTF2 (Affinity Capture-MS), CSTF2 (Affinity Capture-MS), CSTF2 (Affinity Capture-MS), CSTF2 (Affinity Capture-MS)

ESM2 similar proteins: A7EYK3, A7SEP9, A8NYM5, A8XW44, B0JYS7, B7Q2M2, C0NN85, C3Z1P5, C5XYW4, C5XZK6, C7YRT4, D0NHA2, D3B3B7, D3ZCL3, D5GDH4, E0VI98, E1C6F0, E2RGI3, E3KIY6, E3LAN7, E3X5D6, F6HQ26, F6TFD9, F7ARS3, O43670, P09234, P33240, P90815, Q03369, Q16IW3, Q1K7T5, Q1RLC9, Q298E0, Q32PA0, Q4N6K2, Q4WQM6, Q56XE4, Q5BBX9, Q5KC16, Q5R8K4

Diamond homologs: A0A0F6MY85, O02008, P19018, P33240, Q05AT9, Q16560, Q1LZH0, Q4KMD3, Q5RDA3, Q5U1W5, Q8BIQ5, Q8C7E9, Q8HXM1, Q8LPQ9, Q9D384, Q9H0L4, Q9SHZ6, A0A8M1NHK4, A0AV96, A0JM51, A4FV72, A4QUF0, A8WLV5, O01671, O04425, O43040, O43390, O60506, P28659, P86049, Q08BH5, Q08E07, Q0P4R6, Q0V9L3, Q10B98, Q14498, Q28HE9, Q2HJG2, Q2UK72, Q3UEB3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CSTF2	“form complex”	“CSTF complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 96 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	72.5×	8e-12
RNA Polymerase II Transcription Termination	9	31.4×	7e-10
mRNA 3’-end processing	9	28.1×	1e-09
mRNA Polyadenylation	16	22.3×	2e-15
Processing of Capped Intron-Containing Pre-mRNA	9	11.7×	3e-06
mRNA Splicing	6	10.5×	6e-04
Dengue Virus-Host Interactions	13	9.4×	4e-08
mRNA Splicing - Major Pathway	8	6.9×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
mRNA 3’-end processing	5	31.6×	1e-04
mRNA splicing, via spliceosome	7	7.2×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	35
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1526828	GRCh37/hg19 Xq21.32-22.1(chrX:92879337-100099708)	Pathogenic
2423943	NC_000023.10:g.(?99551275)(100099087_?)del	Pathogenic
2692386	NM_001325.3(CSTF2):c.149A>C (p.Asp50Ala)	Pathogenic

SpliceAI

1952 predictions. Top by Δscore:

Variant	Effect	Δscore
X:100821524:TAGTG:T	acceptor_loss	1.0000
X:100821525:A:AG	acceptor_gain	1.0000
X:100821525:AGT:A	acceptor_gain	1.0000
X:100821525:AGTG:A	acceptor_gain	1.0000
X:100821525:AGTGG:A	acceptor_gain	1.0000
X:100821526:G:GA	acceptor_gain	1.0000
X:100821526:GT:G	acceptor_gain	1.0000
X:100821526:GTG:G	acceptor_gain	1.0000
X:100821526:GTGG:G	acceptor_gain	1.0000
X:100821526:GTGGG:G	acceptor_gain	1.0000
X:100821603:CAG:C	donor_loss	1.0000
X:100821604:AG:A	donor_loss	1.0000
X:100821605:GGTGA:G	donor_loss	1.0000
X:100821606:G:GC	donor_loss	1.0000
X:100821607:T:A	donor_loss	1.0000
X:100822241:T:TA	acceptor_gain	1.0000
X:100822248:CA:C	acceptor_loss	1.0000
X:100822249:A:AC	acceptor_loss	1.0000
X:100822249:A:AG	acceptor_gain	1.0000
X:100822249:AGATT:A	acceptor_gain	1.0000
X:100822250:G:GC	acceptor_loss	1.0000
X:100822250:G:GG	acceptor_gain	1.0000
X:100822250:GA:G	acceptor_gain	1.0000
X:100822250:GAT:G	acceptor_gain	1.0000
X:100822250:GATT:G	acceptor_gain	1.0000
X:100822250:GATTG:G	acceptor_gain	1.0000
X:100822416:GAAGA:G	donor_gain	1.0000
X:100822417:AAGA:A	donor_gain	1.0000
X:100822418:AGA:A	donor_gain	1.0000
X:100822419:GA:G	donor_gain	1.0000

AlphaMissense

3736 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:100820465:T:C	S17P	1.000
X:100820466:C:T	S17F	1.000
X:100820468:G:A	V18M	1.000
X:100820469:T:A	V18E	1.000
X:100820471:T:A	F19I	1.000
X:100820471:T:C	F19L	1.000
X:100820471:T:G	F19V	1.000
X:100820472:T:C	F19S	1.000
X:100820472:T:G	F19C	1.000
X:100820473:C:A	F19L	1.000
X:100820473:C:G	F19L	1.000
X:100820474:G:A	V20M	1.000
X:100821527:T:A	V20E	1.000
X:100821529:G:A	G21R	1.000
X:100821529:G:C	G21R	1.000
X:100821529:G:T	G21W	1.000
X:100821530:G:A	G21E	1.000
X:100821530:G:C	G21A	1.000
X:100821530:G:T	G21V	1.000
X:100821532:A:C	N22H	1.000
X:100821532:A:G	N22D	1.000
X:100821533:A:T	N22I	1.000
X:100821534:C:A	N22K	1.000
X:100821534:C:G	N22K	1.000
X:100821535:A:T	I23F	1.000
X:100821536:T:A	I23N	1.000
X:100821536:T:C	I23T	1.000
X:100821536:T:G	I23S	1.000
X:100821538:C:A	P24T	1.000
X:100821539:C:A	P24H	1.000

dbSNP variants (sampled 300 via entrez): RS1000118488 (X:100828410 G>T), RS1000459783 (X:100838449 T>C), RS1000469182 (X:100820010 T>C), RS1000568269 (X:100830714 A>G,T), RS1000633162 (X:100820245 G>A,C,T), RS1000688096 (X:100825221 C>T), RS1000700114 (X:100818533 T>C), RS1000905793 (X:100824530 C>G,T), RS1000914348 (X:100837245 G>A), RS1001323715 (X:100838458 C>A,T), RS1001477325 (X:100827110 A>G), RS1001591499 (X:100821690 A>T), RS1001798052 (X:100829509 T>C), RS1001898965 (X:100840435 C>G), RS1001914273 (X:100829841 G>A)

Disease associations

OMIM: gene MIM:300907 | disease phenotypes: MIM:300088, MIM:301116

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder, X-linked 113	Limited	X-linked

Mondo (2): developmental and epileptic encephalopathy, 9 (MONDO:0010246), intellectual developmental disorder, X-linked 113 (MONDO:0958200)

Orphanet (2): Female restricted epilepsy with intellectual disability (Orphanet:101039), X-linked intellectual disability-epilepsy syndrome (Orphanet:2076)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000750	Delayed speech and language development
HP:0001256	Mild intellectual disability
HP:0001270	Motor delay
HP:0001419	X-linked recessive inheritance
HP:0011463	Childhood onset

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564715	Epilepsy, Female-Restricted, with Mental Retardation (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	3
sodium arsenite	increases expression, affects cotreatment, increases abundance	2
Arsenic	increases methylation, affects cotreatment, increases abundance, increases expression	2
Quercetin	decreases expression	2
Cyclosporine	decreases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
coumarin	increases phosphorylation	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Benztropine	decreases expression	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Clozapine	decreases expression	1
Coumestrol	increases expression	1
Diclofenac	affects expression	1
Doxorubicin	affects expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1PI	Abcam HeLa CSTF2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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