CXXC1

Summary

CXXC1 (CXXC finger protein 1, HGNC:24343) is a protein-coding gene on chromosome 18q21.1, encoding CXXC-type zinc finger protein 1 (Q9P0U4). Transcriptional activator that exhibits a unique DNA binding specificity for CpG unmethylated motifs with a preference for CpGG. It is a selective cancer dependency (DepMap: 31.3% of cell lines).

This gene encodes a protein that functions as a transcriptional activator that binds specifically to non-methylated CpG motifs through its CXXC domain. The protein is a component of the SETD1 complex, regulates gene expression and is essential for vertebrate development.

Source: NCBI Gene 30827 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus (Supportive, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 171 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 31.3% of screened cell lines
• Transcription factor: yes — 21 downstream targets (CollecTRI)
• MANE Select transcript: NM_014593

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24343
Approved symbol	CXXC1
Name	CXXC finger protein 1
Location	18q21.1
Locus type	gene with protein product
Status	Approved
Aliases	HsT2645, PCCX1, hCGBP, PHF18, CGBP, SPP1, CFP1, ZCGPC1
Ensembl gene	ENSG00000154832
Ensembl biotype	protein_coding
OMIM	609150
Entrez	30827

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 34 protein_coding, 10 retained_intron

ENST00000285106, ENST00000412036, ENST00000586144, ENST00000586365, ENST00000586502, ENST00000586568, ENST00000586837, ENST00000587170, ENST00000587342, ENST00000587396, ENST00000589548, ENST00000589940, ENST00000590234, ENST00000590901, ENST00000591190, ENST00000591474, ENST00000592078, ENST00000673786, ENST00000883521, ENST00000883522, ENST00000883523, ENST00000883524, ENST00000883525, ENST00000883526, ENST00000883527, ENST00000883528, ENST00000883529, ENST00000883530, ENST00000883531, ENST00000883532, ENST00000933210, ENST00000933211, ENST00000933212, ENST00000933213, ENST00000933214, ENST00000933215, ENST00000933216, ENST00000933217, ENST00000933218, ENST00000933219, ENST00000945982, ENST00000945983, ENST00000945984, ENST00000945985

RefSeq mRNA: 2 — MANE Select: NM_014593 NM_001101654, NM_014593

CCDS: CCDS11945, CCDS45866

Canonical transcript exons

ENST00000285106 — 15 exons

Exon	Start	End
ENSE00001018029	50286022	50286257
ENSE00001884379	50287587	50287692
ENSE00003500630	50283515	50283564
ENSE00003524418	50285002	50285247
ENSE00003528388	50284732	50284839
ENSE00003546314	50283894	50284101
ENSE00003587324	50285749	50285928
ENSE00003588727	50284378	50284562
ENSE00003606900	50285325	50285351
ENSE00003617659	50283705	50283815
ENSE00003622972	50286539	50286639
ENSE00003653454	50283265	50283361
ENSE00003665159	50282854	50283006
ENSE00003690070	50286740	50286858
ENSE00003910630	50282347	50282739

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.2422 / max 171.3190, expressed in 1807 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171950	17.2209	1804
171951	1.5605	619
171949	1.4608	617

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.68	gold quality
cerebellar hemisphere	UBERON:0002245	98.52	gold quality
cerebellar cortex	UBERON:0002129	98.44	gold quality
body of pancreas	UBERON:0001150	97.87	gold quality
right uterine tube	UBERON:0001302	97.80	gold quality
granulocyte	CL:0000094	97.77	gold quality
pancreatic ductal cell	CL:0002079	97.77	gold quality
cerebellum	UBERON:0002037	97.56	gold quality
metanephros cortex	UBERON:0010533	97.36	gold quality
right lobe of thyroid gland	UBERON:0001119	97.26	gold quality
skin of leg	UBERON:0001511	97.26	gold quality
sural nerve	UBERON:0015488	97.22	gold quality
skin of abdomen	UBERON:0001416	97.10	gold quality
lower esophagus mucosa	UBERON:0035834	96.95	gold quality
left lobe of thyroid gland	UBERON:0001120	96.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.85	gold quality
body of stomach	UBERON:0001161	96.82	gold quality
body of uterus	UBERON:0009853	96.82	gold quality
left adrenal gland cortex	UBERON:0035825	96.82	gold quality
right adrenal gland cortex	UBERON:0035827	96.82	gold quality
right adrenal gland	UBERON:0001233	96.80	gold quality
minor salivary gland	UBERON:0001830	96.68	gold quality
right ovary	UBERON:0002118	96.64	gold quality
left adrenal gland	UBERON:0001234	96.63	gold quality
left ovary	UBERON:0002119	96.61	gold quality
endocervix	UBERON:0000458	96.60	gold quality
transverse colon	UBERON:0001157	96.48	gold quality
mucosa of transverse colon	UBERON:0004991	96.45	gold quality
spleen	UBERON:0002106	96.44	gold quality
adrenal cortex	UBERON:0001235	96.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.73

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

21 targets.

Target	Regulation
ACTA2
ADORA2A
BAG6
BAK1
BDNF
CCNA1
GHRHR
HOXA7
IGFBP3
KLF2
MT1A
NOS2
OPRM1
POMC
PPP1CC
RB1
RELN
SLC12A5
SPN
VIM
YWHAG

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

19 targeting CXXC1, 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-6764-5P	99.75	67.89	2304
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-2276-5P	96.27	65.85	937
HSA-MIR-1238-5P	94.82	67.52	493
HSA-MIR-4758-5P	94.82	67.06	499

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 31.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 14)

• CXXC finger protein 1 is a component of the mammalian Set1 histone H3-Lys4 methyltransferase complex (PMID:16253997)
• CXXC finger protein 1 is required for normal proliferation and differentiation of the PLB-985 myeloid cell line. (PMID:17328666)
• CGBP interacts with MLL1, MLL2 as well as Set1 H3-Lysine 4 (H3K4) specific methyl-transferases and plays critical roles in regulations of MLL target genes. (PMID:18082152)
• study shows endogenous DNMT1 & CFP1 interact in vivo; CFP1 interaction with Setd1A or Setd1B not required for its interaction with DNMT1; result indicates CFP1 intersects cytosine methylation machinery independently of its association with Setd1 complexes (PMID:18680430)
• expression of either the amino half of Cfp1 (amino acids 1 to 367 [Cfp1(1-367)]) or the carboxyl half of Cfp1 (Cfp1(361-656)) is sufficient to correct all of the defects observed with embryonic stem cells that lack Cfp1 (PMID:19433449)
• The crescent-shaped CFP1 CXXC domain is wedged into the major groove of the CpG DNA, distorting the B-form DNA, and interacts extensively with the major groove of the DNA. (PMID:21407193)
• NF-kappaB recruitment enhanced the occupancy of the CpG island within the 14-3-3gamma promoter by CFP1.14-3-3gamma induction in CSR is enabled by the CFP1-mediated H3K4me3 enrichment in the promoter, dependent on NF-kappaB and sustained by E2A. (PMID:23851690)
• directly controls the expression of key genes important for thymocyte survival, such as RORgammat, and for T-cell receptor signaling, including Zap70 and CD8, through maintaining the appropriate H3K4me3 on their promoters (PMID:27210293)
• CFP1 binds open chromatin regions of active genes, including enhancers and non-CpG islands. (PMID:30292235)
• Associations of site-specific CD4(+)-T-cell hypomethylation within CD40-ligand promotor and enhancer regions with disease activity of women with systemic lupus erythematosus. (PMID:33081589)
• Analyzing the impact of CFP1 mutational landscape on epigenetic signaling. (PMID:34320252)
• CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription. (PMID:35864225)
• CFP1 governs uterine epigenetic landscapes to intervene in progesterone responses for uterine physiology and suppression of endometriosis. (PMID:37270588)
• Cfp1 Controls Cardiomyocyte Maturation by Modifying Histone H3K4me3 of Structural, Metabolic, and Contractile Related Genes. (PMID:38196272)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cxxc1a	ENSDARG00000101996
mus_musculus	Cxxc1	ENSMUSG00000024560
rattus_norvegicus	Cxxc1	ENSRNOG00000014614

Paralogs (1): TAF3 (ENSG00000165632)

Protein

Protein identifiers

CXXC-type zinc finger protein 1 — Q9P0U4 (reviewed: Q9P0U4)

Alternative names: CpG-binding protein, PHD finger and CXXC domain-containing protein 1

All UniProt accessions (7): Q9P0U4, A0A669KB29, A0A669KB50, K7EJR0, K7EKZ6, K7EQ21, K7EQZ1

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator that exhibits a unique DNA binding specificity for CpG unmethylated motifs with a preference for CpGG.

Subunit / interactions. Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1 HCFC1 and DPY30. Interacts with SETD1A. Interacts with ZNF335. Interacts with PRDM9; this interaction does not link PRDM9-activated recombination hotspot sites with DSB machinery and is not required for the hotspot recognition pathway. Interacts with histone H3K4me3.

Subcellular location. Nucleus speckle. Nucleus.

Tissue specificity. Ubiquitous.

Post-translational modifications. May be regulated by proteolysis.

Domain organisation. The acidic domain carries the potential to activate transcription.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P0U4-1	1	yes
Q9P0U4-2	2

RefSeq proteins (2): NP_001095124, NP_055408* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR002857	Znf_CXXC	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR022056	CpG-bd_C	Domain
IPR037869	Spp1/CFP1	Family

Pfam: PF00628, PF02008, PF12269

UniProt features (45 total): binding site 8, compositionally biased region 7, modified residue 6, helix 5, region of interest 4, sequence conflict 4, zinc finger region 2, mutagenesis site 2, strand 2, chain 1, cross-link 1, splice variant 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3QMD	X-RAY DIFFRACTION	1.9
3QMB	X-RAY DIFFRACTION	2.06
3QMC	X-RAY DIFFRACTION	2.1
3QMI	X-RAY DIFFRACTION	2.1
3QMG	X-RAY DIFFRACTION	2.3
3QMH	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P0U4-F1	70.66	0.30

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 169; 172; 175; 181; 184; 187; 203; 208

Post-translational modifications (7): 1, 6, 19, 124, 224, 227, 250

Mutagenesis-validated functional residues (2):

Position	Phenotype
169	complete loss of dna binding activity. no effect on localization in nuclear speckles.
208	complete loss of dna binding activity. no effect on localization in nuclear speckles.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes

MSigDB gene sets: 867 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GSE45365_NK_CELL_VS_BCELL_UP, MODULE_52, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_COLLATERAL_SPROUTING, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, TSENG_IRS1_TARGETS_UP, MCLACHLAN_DENTAL_CARIES_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, HARRIS_HYPOXIA, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, ZHAN_MULTIPLE_MYELOMA_MF_UP

GO Biological Process (3): regulation of DNA-templated transcription (GO:0006355), positive regulation of DNA-templated transcription (GO:0045893), chromatin organization (GO:0006325)

GO Molecular Function (7): cis-regulatory region sequence-specific DNA binding (GO:0000987), zinc ion binding (GO:0008270), unmethylated CpG binding (GO:0045322), histone H3K4me3 reader activity (GO:0140002), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear matrix (GO:0016363), nuclear speck (GO:0016607), histone methyltransferase complex (GO:0035097), Set1C/COMPASS complex (GO:0048188), nuclear lumen (GO:0031981)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
IRE1alpha activates chaperones	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA-templated transcription	2
nuclear lumen	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cellular component organization	1
transcription cis-regulatory region binding	1
transition metal ion binding	1
sequence-specific DNA binding	1
histone H3 reader activity	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
nucleoplasm	1
methyltransferase complex	1
nuclear protein-containing complex	1
histone methyltransferase complex	1
nucleus	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

2382 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXXC1	WDR82	Q6UXN9	999
CXXC1	RBBP5	Q15291	997
CXXC1	SETD1A	O15047	995
CXXC1	WDR5	P61964	995
CXXC1	SETD1B	Q9UPS6	984
CXXC1	ASH2L	Q9UBL3	978
CXXC1	PRDM9	Q9NQV7	977
CXXC1	DPY30	Q9C005	973
CXXC1	IHO1	Q8IYA8	904
CXXC1	HCFC1	P51610	831
CXXC1	SDC1	P18827	699
CXXC1	H3-5	Q6NXT2	682
CXXC1	H3-7	Q5TEC6	682
CXXC1	H3C14	Q71DI3	681
CXXC1	H3-4	Q16695	681

IntAct

115 interactions, top by confidence:

A	B	Type	Score
WDR5	KMT2D	psi-mi:“MI:0914”(association)	0.910
WDR5	SETD1A	psi-mi:“MI:0914”(association)	0.880
SETD1A	WDR5	psi-mi:“MI:0914”(association)	0.880
PRPS1	PRPSAP2	psi-mi:“MI:0914”(association)	0.840
RBBP5	KMT2D	psi-mi:“MI:0914”(association)	0.840
NUP50	KPNA4	psi-mi:“MI:0914”(association)	0.830
CXXC1	RBBP5	psi-mi:“MI:0915”(physical association)	0.790
CXXC1	SETD1A	psi-mi:“MI:0914”(association)	0.760
ASH2L	SETD1A	psi-mi:“MI:0914”(association)	0.760
WDR5	MEN1	psi-mi:“MI:0914”(association)	0.710
PSMC3	PSMD12	psi-mi:“MI:0914”(association)	0.640
DPY30	AKAP8	psi-mi:“MI:0914”(association)	0.610
TP53	CXXC1	psi-mi:“MI:0914”(association)	0.600
CXXC1	TP53	psi-mi:“MI:0914”(association)	0.600
TP53	CXXC1	psi-mi:“MI:0915”(physical association)	0.600
CXXC1	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
TAX1BP1	CXXC1	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	CXXC1	psi-mi:“MI:0915”(physical association)	0.560
CXXC1	TAX1BP1	psi-mi:“MI:0915”(physical association)	0.560
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530

BioGRID (296): SETD1A (Affinity Capture-Western), ASH2L (Affinity Capture-Western), RBBP5 (Affinity Capture-Western), WDR5 (Affinity Capture-Western), WDR82 (Affinity Capture-Western), CXXC1 (Reconstituted Complex), CXXC1 (Two-hybrid), CXXC1 (Two-hybrid), CXXC1 (Affinity Capture-Western), CXXC1 (Affinity Capture-Western), ASH2L (Affinity Capture-Western), RBBP5 (Affinity Capture-Western), WDR5 (Affinity Capture-Western), SETD1A (Affinity Capture-Western), SETD1B (Affinity Capture-Western)

ESM2 similar proteins: A0A286Y9D1, A0JMK9, A2BIL7, A8DZJ1, B2KF05, B2RRD7, B4KLY7, F4IDY7, O15042, O94880, O97159, P55201, P97496, Q05913, Q20448, Q2T9V9, Q3T095, Q4V7A6, Q5EA28, Q5R7X2, Q61103, Q63ZP1, Q6DD45, Q6FSB1, Q6GQJ2, Q6IE81, Q6IE82, Q6NV83, Q6NWE1, Q6P2L6, Q6ZPI0, Q7KRW8, Q7ZVP1, Q803A0, Q8BRB7, Q8WML3, Q8WUB8, Q92613, Q92785, Q92922

Diamond homologs: A2WXR5, A2XTW9, A2Y0Q2, A2Y4R8, B8ADZ3, B8AMA8, B8B8C5, B8B8I3, B8BJV8, O74508, O81488, Q12830, Q2R837, Q40359, Q5EA28, Q5XEM9, Q60DW3, Q6BER5, Q6YTY3, Q6Z7F4, Q75IR6, Q7F2Z1, Q7XUW3, Q80TJ7, Q84TV4, Q8C9B9, Q8H383, Q8LA16, Q8S8M9, Q9BTC0, Q9CWW7, Q9FFF5, Q9M2B4, Q9P0U4, Q9SRM4, Q9UPP1, Q9W0T1, Q9W352, P0CF52, P0CH95

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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
Formation of WDR5-containing histone-modifying complexes	14	45.3×	1e-17
Deactivation of the beta-catenin transactivating complex	6	17.1×	8e-05
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	11	16.1×	1e-08
Formation of the beta-catenin:TCF transactivating complex	10	14.7×	2e-07
PKMTs methylate histone lysines	7	13.7×	7e-05
Transcriptional regulation by RUNX1	7	12.5×	8e-05
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	7	12.5×	8e-05
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	5	12.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
transcription initiation-coupled chromatin remodeling	7	23.7×	1e-05
DNA damage response	10	4.7×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	114
Likely benign	15
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

2056 predictions. Top by Δscore:

Variant	Effect	Δscore
18:50282737:CCA:C	acceptor_gain	1.0000
18:50282738:CAC:C	acceptor_gain	1.0000
18:50282740:C:CC	acceptor_gain	1.0000
18:50282847:AACCT:A	donor_loss	1.0000
18:50282849:CCT:C	donor_loss	1.0000
18:50282850:CTACC:C	donor_loss	1.0000
18:50282852:A:AC	donor_gain	1.0000
18:50282852:ACCAC:A	donor_loss	1.0000
18:50282853:C:CC	donor_gain	1.0000
18:50282853:CCA:C	donor_gain	1.0000
18:50282853:CCACA:C	donor_gain	1.0000
18:50282862:CGCG:C	donor_gain	1.0000
18:50282879:T:TA	donor_gain	1.0000
18:50283002:GGCAC:G	acceptor_gain	1.0000
18:50283003:GCAC:G	acceptor_gain	1.0000
18:50283004:CAC:C	acceptor_gain	1.0000
18:50283004:CACC:C	acceptor_gain	1.0000
18:50283005:AC:A	acceptor_gain	1.0000
18:50283006:CC:C	acceptor_gain	1.0000
18:50283006:CCT:C	acceptor_loss	1.0000
18:50283007:C:CC	acceptor_gain	1.0000
18:50283007:C:CG	acceptor_loss	1.0000
18:50283010:C:CT	acceptor_gain	1.0000
18:50283019:CAGGT:C	acceptor_gain	1.0000
18:50283263:A:AC	donor_gain	1.0000
18:50283264:C:CC	donor_gain	1.0000
18:50283565:C:CC	acceptor_gain	1.0000
18:50283704:CCTTG:C	donor_loss	1.0000
18:50283714:G:C	donor_gain	1.0000
18:50283811:TTGCT:T	acceptor_gain	1.0000

AlphaMissense

4297 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:50282650:G:C	H638Q	1.000
18:50282650:G:T	H638Q	1.000
18:50282651:T:C	H638R	1.000
18:50282652:G:C	H638D	1.000
18:50282654:A:G	L637P	1.000
18:50282654:A:T	L637Q	1.000
18:50282657:A:C	M636R	1.000
18:50282657:A:T	M636K	1.000
18:50282660:A:G	L635P	1.000
18:50282660:A:T	L635Q	1.000
18:50282666:A:G	L633P	1.000
18:50282669:A:G	L632S	1.000
18:50282672:C:T	G631E	1.000
18:50282673:C:G	G631R	1.000
18:50282673:C:T	G631R	1.000
18:50282678:C:A	R629L	1.000
18:50282678:C:G	R629P	1.000
18:50282679:G:A	R629C	1.000
18:50282679:G:T	R629S	1.000
18:50282691:C:G	A625P	1.000
18:50282696:C:G	R623P	1.000
18:50282705:C:G	R620P	1.000
18:50282706:G:T	R620S	1.000
18:50282709:C:T	E619K	1.000
18:50282711:T:G	Q618P	1.000
18:50282715:C:T	E617K	1.000
18:50282720:A:G	L615P	1.000
18:50282726:T:A	D613V	1.000
18:50282726:T:G	D613A	1.000
18:50282727:C:A	D613Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000043942 (18:50282078 C>A,T), RS1000251443 (18:50288900 A>G), RS1000447135 (18:50283204 A>G,T), RS1000480070 (18:50282834 A>C,G), RS1000727416 (18:50288703 T>A,C,G), RS1001147273 (18:50283845 G>A), RS1001165530 (18:50284195 G>A,C), RS1001515921 (18:50288077 G>A,C), RS1001818534 (18:50288329 T>C), RS1002120995 (18:50282331 T>C), RS1002158736 (18:50287184 C>T), RS1002837505 (18:50285605 CT>C), RS1003825041 (18:50285653 A>G), RS1004045816 (18:50288735 A>G), RS1005361761 (18:50283555 G>A)

Disease associations

OMIM: gene MIM:609150 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
systemic lupus erythematosus	Supportive	Unknown

Mondo (1): systemic lupus erythematosus (MONDO:0007915)

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001713_23	Dental caries	7.000000e-08
GCST004146_27	Chronic lymphocytic leukemia	3.000000e-08
GCST006585_2474	Blood protein levels	1.000000e-07
GCST008971_60	Urate levels	6.000000e-10
GCST012338_14	Gout	3.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169201 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
manganese chloride	decreases expression, increases methylation, affects cotreatment, increases abundance	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
bisphenol S	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	decreases methylation	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Asbestos	increases expression	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Rotenone	decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Triclosan	increases expression	1
Zinc	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Asbestos, Amosite	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5126416	Binding	Inhibition of GST-tagged human CGBP (161 to 217 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay	Small-Molecule Inhibitors of the MLL1 CXXC Domain, an Epigenetic Reader of DNA Methylation. — ACS Med Chem Lett

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7WY	Abcam Raji CXXC1 KO	Cancer cell line	Male
CVCL_B9XJ	Abcam THP-1 CXXC1 KO	Cancer cell line	Male
CVCL_C6ZE	Abcam PC-3 CXXC1 KO	Cancer cell line	Male
CVCL_D9CT	Ubigene HEK293 CXXC1 KO	Transformed cell line	Female
CVCL_SK22	HAP1 CXXC1 (-) 1	Cancer cell line	Male
CVCL_SK23	HAP1 CXXC1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00120887	PHASE4	COMPLETED	Lupus Atherosclerosis Prevention Study
NCT00125307	PHASE4	COMPLETED	Tacrolimus for the Treatment of Systemic Lupus Erythematosus With Membranous Nephritis
NCT00188188	PHASE4	UNKNOWN	Study of Endothelial Dysfunction in Systemic Lupus and Its Role in Heart Disease
NCT00371501	PHASE4	COMPLETED	Aspirin and Statins for Prevention of Atherosclerosis and Arterial Thromboembolism in Systemic Lupus Erythematosus
NCT00392093	PHASE4	COMPLETED	Effect of Hormone Replacement Therapy on Lupus Activity
NCT00413361	PHASE4	COMPLETED	The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
NCT00508898	PHASE4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00668330	PHASE4	COMPLETED	Steroid Induced Osteoporosis in Patients With Systemic Lupus Erythematosus
NCT00739050	PHASE4	TERMINATED	Effect of Simvastatin on Endothelial Function in Premenopausal Women With Systemic Lupus Erythematosus (0733-271)(TERMINATED)
NCT00815282	PHASE4	COMPLETED	Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
NCT00828178	PHASE4	COMPLETED	Efficacy of Fish Oil in Lupus Patients
NCT00866229	PHASE4	UNKNOWN	Efficacy and Adverse Effect of Simvastatin Compare to Rosuvastatin in Systemic Lupus Erythematosus (SLE) Patients With Corticosteroid Therapy and High Low-Density Lipoprotein (LDL) Cholesterol Level
NCT00911521	PHASE4	COMPLETED	Immunogenicity and Safety of a Quadrivalent Human Papillomavirus (HPV) Vaccine in Patients With SLE: a Controlled Study
NCT01101802	PHASE4	COMPLETED	Mycophenolate Mofetil in Systemic Lupus Erythematosus (MISSILE)
NCT01112215	PHASE4	COMPLETED	Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01276782	PHASE4	WITHDRAWN	Levothyroxine in Pregnant SLE Patients
NCT01322308	PHASE4	COMPLETED	Effect of Pioglitazone on Endothelial Function in Premenopausal Women With Uncomplicated Systemic Lupus Erythematosus
NCT01359826	PHASE4	WITHDRAWN	The Effect of Milnacipran on Fatigue and Quality of Life in Lupus Patients
NCT01597492	PHASE4	COMPLETED	A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)
NCT01632241	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
NCT01705977	PHASE4	COMPLETED	Belimumab Assessment of Safety in SLE
NCT01753401	PHASE4	COMPLETED	Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
NCT02270970	PHASE4	UNKNOWN	Evaluation of Belimumab Impact on a BLyS Activity Signature Test in the Absence of Confounding Polypharmacy
NCT02477150	PHASE4	COMPLETED	Safety and Immunogenicity of a Zoster Vaccine in SLE
NCT02741960	PHASE4	COMPLETED	The Effect of Metformin on Reducing Lupus Flares
NCT02779153	PHASE4	WITHDRAWN	Acthar SLE (Systemic Lupus Erythematosus)
NCT02953821	PHASE4	COMPLETED	Acthar Gel for Active Systemic Lupus Erythematosus (SLE)
NCT03042260	PHASE4	UNKNOWN	Prophylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous
NCT03098823	PHASE4	COMPLETED	A Crossover Study to Compare RAYOS to IR Prednisone to Improve Fatigue and Morning Symptoms for SLE
NCT03122431	PHASE4	COMPLETED	Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases
NCT03543839	PHASE4	RECRUITING	Trial of Belimumab in Early Lupus
NCT04447053	PHASE4	UNKNOWN	Sequential Belimumab and T-cell Based Therapy in SLE
NCT04515719	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in SLE Patients
NCT04893161	PHASE4	UNKNOWN	A Model About the Response of Belimumab in SLE
NCT04908865	PHASE4	COMPLETED	Open-label Study of Belimumab Plus Standard Therapy in Chinese Pediatric Participants With Active Systemic Lupus Erythematosus (SLE)
NCT04956484	PHASE4	COMPLETED	Belimumab In Early Systemic Lupus Erythematosus
NCT05559671	PHASE4	RECRUITING	Safety of the Herpes Zoster Subunit Vaccine in Lupus
NCT05666336	PHASE4	UNKNOWN	Multi-omics Studies on the Efficacy of Telitacicept in Chinese SLE Patients
NCT05748925	PHASE4	COMPLETED	Cardio Renal Effects of SGLT2 Inhibitors Among Lupus Nephritis Patients