CXXC5

Summary

CXXC5 (CXXC finger protein 5, HGNC:26943) is a protein-coding gene on chromosome 5q31.2, encoding CXXC-type zinc finger protein 5 (Q7LFL8). May indirectly participate in activation of the NF-kappa-B and MAPK pathways.

The protein encoded by this gene is a retinoid-inducible nuclear protein containing a CXXC-type zinc finger motif. The encoded protein is involved in myelopoiesis, is required for DNA damage-induced p53 activation, regulates the differentiation of C2C12 myoblasts into myocytes, and negatively regulates cutaneous wound healing. Several transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 51523 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 52 total
• Druggable target: yes
• MANE Select transcript: NM_016463

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26943
Approved symbol	CXXC5
Name	CXXC finger protein 5
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	HSPC195, RINF, WID
Ensembl gene	ENSG00000171604
Ensembl biotype	protein_coding
OMIM	612752
Entrez	51523

Gene structure

Transcript identifiers

Ensembl transcripts: 50 — 48 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000302517, ENST00000502295, ENST00000502336, ENST00000502716, ENST00000503511, ENST00000504844, ENST00000504944, ENST00000505812, ENST00000507139, ENST00000509238, ENST00000511048, ENST00000511457, ENST00000511591, ENST00000512816, ENST00000515038, ENST00000520967, ENST00000897220, ENST00000897221, ENST00000897222, ENST00000897223, ENST00000897224, ENST00000897225, ENST00000897226, ENST00000897227, ENST00000897228, ENST00000897229, ENST00000897230, ENST00000897231, ENST00000897232, ENST00000897233, ENST00000897234, ENST00000937605, ENST00000937606, ENST00000937607, ENST00000937608, ENST00000937609, ENST00000937610, ENST00000937611, ENST00000937612, ENST00000937613, ENST00000937614, ENST00000937615, ENST00000964239, ENST00000964240, ENST00000964241, ENST00000964242, ENST00000964243, ENST00000964244, ENST00000964245, ENST00000964246

RefSeq mRNA: 14 — MANE Select: NM_016463 NM_001317199, NM_001317200, NM_001317201, NM_001317202, NM_001317203, NM_001317204, NM_001317205, NM_001317206, NM_001317207, NM_001317208, NM_001317209, NM_001317210, NM_001317211, NM_016463

CCDS: CCDS43370

Canonical transcript exons

ENST00000302517 — 3 exons

Exon	Start	End
ENSE00001157178	139680364	139681447
ENSE00001416093	139648349	139648845
ENSE00001419996	139682863	139683882

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 99.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.0552 / max 295.4986, expressed in 1751 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58855	26.4232	1687
58857	6.3359	1335
58854	5.3632	1475
58856	0.7651	447
58863	0.5563	276
58858	0.5288	203
58862	0.0408	5
58860	0.0333	4
58861	0.0085	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	99.60	gold quality
pancreatic ductal cell	CL:0002079	98.96	gold quality
renal medulla	UBERON:0000362	98.81	gold quality
inferior vagus X ganglion	UBERON:0005363	98.67	gold quality
medulla oblongata	UBERON:0001896	98.42	gold quality
ventral tegmental area	UBERON:0002691	98.24	gold quality
cerebellum	UBERON:0002037	98.15	gold quality
superior vestibular nucleus	UBERON:0007227	98.15	gold quality
pons	UBERON:0000988	98.12	gold quality
nasal cavity epithelium	UBERON:0005384	98.12	gold quality
cerebellar hemisphere	UBERON:0002245	98.07	gold quality
cerebellar cortex	UBERON:0002129	98.05	gold quality
subthalamic nucleus	UBERON:0001906	98.01	gold quality
parietal lobe	UBERON:0001872	97.99	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.99	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.97	gold quality
postcentral gyrus	UBERON:0002581	97.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.83	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.52	gold quality
superior frontal gyrus	UBERON:0002661	97.33	gold quality
epithelial cell of pancreas	CL:0000083	97.30	gold quality
entorhinal cortex	UBERON:0002728	97.18	gold quality
tibialis anterior	UBERON:0001385	97.05	gold quality
trigeminal ganglion	UBERON:0001675	97.02	gold quality
spinal cord	UBERON:0002240	96.90	gold quality
occipital lobe	UBERON:0002021	96.88	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.81	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.75	gold quality
dorsal root ganglion	UBERON:0000044	96.70	gold quality
prefrontal cortex	UBERON:0000451	96.64	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	53.42
E-HCAD-10	yes	30.91
E-HCAD-13	yes	27.14
E-HCAD-5	yes	22.13
E-ANND-3	yes	15.15
E-MTAB-7316	yes	13.30
E-MTAB-9467	yes	11.77
E-CURD-114	yes	7.11
E-GEOD-137537	yes	5.42
E-MTAB-11121	no	903.64
E-CURD-112	no	2.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): WT1

miRNA regulators (miRDB)

94 targeting CXXC5, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-1208	99.70	68.28	1533

Literature-anchored findings (GeneRIF, showing 24)

• RINF expression correlates with retinoid-induced differentiation of leukemic cells and with cytokine-induced myelopoiesis of normal CD34(+) progenitors. (PMID:19182210)
• These findings suggest that CF5 plays a crucial role in ATM-p53 signaling in response to DNA damage. (PMID:19557330)
• RINF overexpression represents an independent molecular marker for poor prognosis in breast tumors. (PMID:21325450)
• Lack of promoter hypermethylation or somatic mutations are found in the potential tumor suppressor CXXC5 in myelodysplastic syndromes or acute myeloid leukemia with deletion 5q. (PMID:23190153)
• targeting of CXXC5/RINF should be considered as a possible therapeutic strategy, especially in high-risk patients who show increased expression in AML cells compared with normal hematopoietic cells (PMID:23988457)
• Findings suggest that overexpression of CXXC5 in C2C12 myoblasts facilitated myocyte differentiation, while RNAi interference of CXXC5 significantly inhibited the differentiation of C2C12 myoblasts. (PMID:25433557)
• High CXXC5 expression seems to affect several steps in human leukemogenesis, including intracellular events as well as extracellular communication. (PMID:25605239)
• Low CXXC5 expression is associated with acute myeloid leukemia. (PMID:25805812)
• show here that CXXC5 is an E2-ERalpha responsive gene regulated by the interaction of E2-ERalpha with an ERE present at a region upstream of the initial translation codon of the gene (PMID:27886276)
• KANK1 inhibits Malignant peripheral nerve sheath tumors cell growth though CXXC5 mediated apoptosis. (PMID:28067315)
• Knockdown of CXXC5 attenuated the expression of a substantial portion of TGF-beta target genes and ameliorated TGF-beta-induced growth inhibition or apoptosis of Hep3B cells, suggesting that CXXC5 is required for TGF-beta-mediated inhibition of hepatocellular carcinoma (HCC) progression. (PMID:29036306)
• NUDT21 inhibits HCC proliferation, metastasis and tumorigenesis, at least in part, by suppressing PSMB2 and CXXC5. (PMID:29780166)
• CXXC5 is direct target gene of miR-32 which binds its 3’-UTR and inhibited the expression level of CXXC5 mRNA and protein. (PMID:30362164)
• CXXC5 is a a novel regulator and coordinator of TGF-beta, BMP4 and Wnt3a signaling. (Review) (PMID:30479059)
• These results reveal an important role for CXXC5 as a suppressor of longitudinal bone growth involving growth plate activity. (PMID:30971423)
• The epigenetic regulator RINF (CXXC5) maintains SMAD7 expression in human immature erythroid cells and sustains red blood cells expansion. (PMID:33241676)
• A prelude to the proximity interaction mapping of CXXC5. (PMID:34475492)
• Inhibition of CXXC5 function reverses obesity-related metabolic diseases. (PMID:35384342)
• Context-dependent tumor-suppressive BMP signaling in diffuse intrinsic pontine glioma regulates stemness through epigenetic regulation of CXXC5. (PMID:35915262)
• Zinc-finger protein CXXC5 promotes breast carcinogenesis by regulating the TSC1/mTOR signaling pathway. (PMID:36539038)
• CXXC5 Mediates DHT-Induced Androgenetic Alopecia via PGD2. (PMID:36831222)
• Inhibition of CXXC5 function rescues Alzheimer’s disease phenotypes by restoring Wnt/beta-catenin signaling pathway. (PMID:37355147)
• Inhibiting the cytosolic function of CXXC5 accelerates diabetic wound healing by enhancing angiogenesis and skin repair. (PMID:37524876)
• CXXC5 drove inflammation and ovarian cancer proliferation via transcriptional activation of ZNF143 and EGR1. (PMID:38642782)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cxxc5b	ENSDARG00000075735
danio_rerio	cxxc5a	ENSDARG00000078865
mus_musculus	Cxxc5	ENSMUSG00000046668
rattus_norvegicus	Cxxc5l1	ENSRNOG00000003734
rattus_norvegicus	Cxxc5	ENSRNOG00000032878

Paralogs (1): CXXC4 (ENSG00000168772)

Protein

Protein identifiers

CXXC-type zinc finger protein 5 — Q7LFL8 (reviewed: Q7LFL8)

Alternative names: Putative MAPK-activating protein PM08, Putative NF-kappa-B-activating protein 102, Retinoid-inducible nuclear factor

All UniProt accessions (13): A0A1D5RMR5, D6R966, D6R9V1, D6RBE0, D6RCN9, D6RDY2, D6RHC6, D6RHG9, D6RIR8, D6RJC1, E7EV55, E7EVI8, Q7LFL8

UniProt curated annotations — full annotation on UniProt →

Function. May indirectly participate in activation of the NF-kappa-B and MAPK pathways. Acts as a mediator of BMP4-mediated modulation of canonical Wnt signaling activity in neural stem cells. Required for DNA damage-induced ATM phosphorylation, p53 activation and cell cycle arrest. Involved in myelopoiesis. Transcription factor. Binds to the oxygen responsive element of COX4I2 and represses its transcription under hypoxia conditions (4% oxygen), as well as normoxia conditions (20% oxygen). May repress COX4I2 transactivation induced by CHCHD2 and RBPJ. Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG.

Subunit / interactions. Interacts with DVL1. Interacts with RBPJ.

Subcellular location. Nucleus. Cytoplasm.

Domain organisation. The CXXC zinc finger mediates binding to CpG-DNA.

Induction. By retinoic acid.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7LFL8-1	1	yes
Q7LFL8-2	2

RefSeq proteins (14): NP_001304128, NP_001304129, NP_001304130, NP_001304131, NP_001304132, NP_001304133, NP_001304134, NP_001304135, NP_001304136, NP_001304137, NP_001304138, NP_001304139, NP_001304140, NP_057547* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002857	Znf_CXXC	Domain
IPR040388	CXXC4/CXXC5	Family

Pfam: PF02008

UniProt features (25 total): binding site 8, helix 4, compositionally biased region 4, chain 1, zinc finger region 1, modified residue 1, splice variant 1, sequence conflict 1, region of interest 1, strand 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5W9S	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7LFL8-F1	60.50	0.14

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): 269; 275; 278; 281; 291; 296; 263; 266

Post-translational modifications (1): 53

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9018519	Estrogen-dependent gene expression

MSigDB gene sets: 309 (showing top): RRAGTTGT_UNKNOWN, FREAC2_01, WANG_CLIM2_TARGETS_UP, RORA1_01, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, AREB6_01, TGACCTY_ERR1_Q2, AP2_Q3, FOXO1_01, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, MARTINEZ_RB1_TARGETS_DN, ROZANOV_MMP14_TARGETS_UP, BILD_E2F3_ONCOGENIC_SIGNATURE

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), regulation of generation of precursor metabolites and energy (GO:0043467)

GO Molecular Function (6): zinc ion binding (GO:0008270), methyl-CpG binding (GO:0008327), sequence-specific DNA binding (GO:0043565), DNA-binding transcription factor binding (GO:0140297), DNA binding (GO:0003677), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
ESR-mediated signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
generation of precursor metabolites and energy	1
regulation of metabolic process	1
transition metal ion binding	1
nucleotide binding	1
sequence-specific DNA binding	1
DNA binding	1
transcription factor binding	1
nucleic acid binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXXC5	DVL1	O14640	960
CXXC5	TET2	Q6N021	946
CXXC5	ATP6AP1	Q15904	700
CXXC5	ATP5PF	P18859	690
CXXC5	AXIN2	Q9Y2T1	585
CXXC5	WNT3A	P56704	578
CXXC5	BMP4	P12644	557
CXXC5	SUV39H1	O43463	523
CXXC5	TET1	Q8NFU7	497
CXXC5	KDM2B	Q8NHM5	497
CXXC5	NANOG	Q9H9S0	468
CXXC5	POU5F1	P31359	457
CXXC5	CXXC4	Q9H2H0	452
CXXC5	BEND2	Q8NDZ0	448
CXXC5	RFX1	P22670	410

IntAct

19 interactions, top by confidence:

A	B	Type	Score
VDR	CXXC5	psi-mi:“MI:0915”(physical association)	0.370
CXXC5	SKIL	psi-mi:“MI:0915”(physical association)	0.370
SMAD3	CXXC5	psi-mi:“MI:0915”(physical association)	0.370
CXXC5	SMAD7	psi-mi:“MI:0915”(physical association)	0.370
SMAD5	CXXC5	psi-mi:“MI:0915”(physical association)	0.370
CXXC5	SMAD9	psi-mi:“MI:0915”(physical association)	0.370
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CELF1	CXXC5	psi-mi:“MI:0915”(physical association)	0.000
FMR1	CXXC5	psi-mi:“MI:0915”(physical association)	0.000
KCNJ6	CXXC5	psi-mi:“MI:0915”(physical association)	0.000
DSCAM	CXXC5	psi-mi:“MI:0915”(physical association)	0.000
UBASH3A	CXXC5	psi-mi:“MI:0915”(physical association)	0.000
HUNK	CXXC5	psi-mi:“MI:0915”(physical association)	0.000
DSCR9	CXXC5	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	CXXC5	psi-mi:“MI:0915”(physical association)	0.000
RCAN1	CXXC5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): CXXC5 (Affinity Capture-Western), CXXC5 (Affinity Capture-RNA), CXXC5 (Affinity Capture-MS), CXXC5 (Affinity Capture-MS), CXXC5 (Two-hybrid), CXXC5 (Two-hybrid), CXXC5 (Two-hybrid), CXXC5 (Two-hybrid), CXXC5 (Two-hybrid), CXXC5 (Two-hybrid), CXXC5 (Two-hybrid), CXXC5 (Affinity Capture-MS), CXXC5 (Proximity Label-MS), CXXC5 (Reconstituted Complex), CXXC5 (Two-hybrid)

ESM2 similar proteins: A0A060D764, A2WM14, A2WV68, A2XMN1, A2XYN9, A2YFT9, A2YXQ1, B8AX53, O23875, O64647, P48000, Q01KM7, Q0DAE8, Q0E342, Q0J6N4, Q0J995, Q0JNI9, Q10CE8, Q10EC6, Q10ED2, Q17308, Q53PH2, Q5NAN5, Q5R7N4, Q5VRW2, Q5Z5I4, Q652B0, Q688U3, Q6ER21, Q6YXH5, Q6YZE8, Q6Z869, Q6ZBH6, Q7EXZ2, Q7LFL8, Q7X7N3, Q7XPY1, Q8IVW6, Q8LN68, Q8LT05

Diamond homologs: A0A1L8GSA2, A0JP82, K9JHZ4, M9NEY8, O43151, Q0VFP6, Q32LB3, Q4JK59, Q5R7N4, Q5XIQ3, Q6N021, Q6NXI8, Q7LFL8, Q800L6, Q8BG87, Q8NFU7, Q91WA4, Q9EQC9, Q9H2H0, Q3URK3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 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
Signaling by TGFB family members	5	57.7×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
transforming growth factor beta receptor signaling pathway	5	49.7×	5e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

867 predictions. Top by Δscore:

Variant	Effect	Δscore
5:139681445:G:GT	donor_gain	1.0000
5:139682851:C:A	acceptor_gain	1.0000
5:139680363:GA:G	acceptor_gain	0.9900
5:139681362:GTT:G	donor_gain	0.9900
5:139681445:GAGG:G	donor_loss	0.9900
5:139681446:AGGTA:A	donor_loss	0.9900
5:139681447:GGTA:G	donor_loss	0.9900
5:139681448:G:GA	donor_loss	0.9900
5:139681449:T:G	donor_loss	0.9900
5:139682844:T:TA	acceptor_gain	0.9900
5:139682857:C:CA	acceptor_gain	0.9900
5:139682861:AGAAG:A	acceptor_gain	0.9900
5:139682862:GAA:G	acceptor_gain	0.9900
5:139682862:GAAGG:G	acceptor_gain	0.9900
5:139648842:GCCG:G	donor_gain	0.9800
5:139682858:GCCA:G	acceptor_loss	0.9800
5:139682859:CCA:C	acceptor_loss	0.9800
5:139682860:CA:C	acceptor_loss	0.9800
5:139682861:A:AG	acceptor_gain	0.9800
5:139682861:A:C	acceptor_loss	0.9800
5:139682862:G:GA	acceptor_gain	0.9800
5:139682862:GA:G	acceptor_gain	0.9800
5:139648843:CCGG:C	donor_loss	0.9700
5:139648844:CGGTA:C	donor_loss	0.9700
5:139648847:T:A	donor_loss	0.9700
5:139650063:G:GT	donor_gain	0.9700
5:139649906:G:T	donor_gain	0.9600
5:139650147:G:GT	donor_gain	0.9600
5:139680362:A:AG	acceptor_gain	0.9600
5:139680363:G:GG	acceptor_gain	0.9600

AlphaMissense

2111 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:139681185:T:C	F221S	1.000
5:139681298:A:G	K259E	1.000
5:139681300:G:C	K259N	1.000
5:139681300:G:T	K259N	1.000
5:139681301:C:G	R260G	1.000
5:139681301:C:T	R260W	1.000
5:139681302:G:T	R260L	1.000
5:139681304:A:G	K261E	1.000
5:139681305:A:T	K261I	1.000
5:139681306:A:C	K261N	1.000
5:139681306:A:T	K261N	1.000
5:139681307:C:A	R262S	1.000
5:139681307:C:G	R262G	1.000
5:139681307:C:T	R262C	1.000
5:139681308:G:T	R262L	1.000
5:139681310:T:A	C263S	1.000
5:139681310:T:C	C263R	1.000
5:139681311:G:A	C263Y	1.000
5:139681311:G:C	C263S	1.000
5:139681311:G:T	C263F	1.000
5:139681312:C:G	C263W	1.000
5:139681313:G:C	G264R	1.000
5:139681313:G:T	G264C	1.000
5:139681314:G:A	G264D	1.000
5:139681314:G:T	G264V	1.000
5:139681319:T:A	C266S	1.000
5:139681319:T:C	C266R	1.000
5:139681320:G:A	C266Y	1.000
5:139681320:G:C	C266S	1.000
5:139681320:G:T	C266F	1.000

dbSNP variants (sampled 300 via entrez): RS1000029534 (5:139661471 C>T), RS1000071704 (5:139663996 T>A), RS1000212858 (5:139655821 G>A,C), RS1000316909 (5:139673241 A>G), RS1000396736 (5:139661302 G>A), RS1000451615 (5:139677378 C>T), RS1000553345 (5:139657195 A>G), RS1000616847 (5:139683640 T>C), RS1000675948 (5:139671501 A>G), RS1000731858 (5:139677662 A>C), RS1000745487 (5:139661162 C>T), RS1000887267 (5:139666022 A>G), RS1001028365 (5:139683912 G>A,C,T), RS1001138691 (5:139662677 G>C), RS1001195007 (5:139672816 G>T)

Disease associations

OMIM: gene MIM:612752 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002783_46	Body mass index	5.000000e-06
GCST007239_8	Ovarian cancer	8.000000e-06
GCST010002_39	Refractive error	2.000000e-14
GCST010988_343	Adult body size	2.000000e-12
GCST012227_192	Hip circumference adjusted for BMI	1.000000e-09
GCST90000025_18	Appendicular lean mass	1.000000e-16

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169170 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 8 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.32	IC50	4800	nM	CHEMBL5194845

PubChem BioAssay actives

1 with measured affinity, of 9 total; 1 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-phenyl-1-prop-2-enoylpiperidine-4-carboxylic acid	1871104: Inhibition of GST-tagged human CXXC5 (255 to 305 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay	ic50	4.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	5
trichostatin A	affects cotreatment, increases expression	3
methylmercuric chloride	increases expression	2
bisphenol A	increases expression, affects cotreatment, decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
perfluorooctane sulfonic acid	decreases expression	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, affects response to substance	2
Arsenic	increases methylation, affects cotreatment, decreases expression, increases abundance	2
Estradiol	affects expression, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	increases expression, affects cotreatment	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression, increases abundance, affects cotreatment	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	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
CHEMBL5126415	Binding	Inhibition of GST-tagged human CXXC5 (255 to 305 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

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0V6	SEES3-1V human CXXC5, clone1	Embryonic stem cell	Male
CVCL_A0V7	SEES3-1V human CXXC5, clone2	Embryonic stem cell	Male
CVCL_A0V8	SEES3-1V human CXXC5, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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