CTCFL

Summary

CTCFL (CCCTC-binding factor like, HGNC:16234) is a protein-coding gene on chromosome 20q13.31, encoding Transcriptional repressor CTCFL (Q8NI51). Testis-specific DNA binding protein responsible for insulator function, nuclear architecture and transcriptional control, which probably acts by recruiting epigenetic chromatin modifiers.

CCCTC-binding factor (CTCF), an 11-zinc-finger factor involved in gene regulation, utilizes different zinc fingers to bind varying DNA target sites. CTCF forms methylation-sensitive insulators that regulate X-chromosome inactivation. This gene is a paralog of CTCF and appears to be expressed primarily in the cytoplasm of spermatocytes, unlike CTCF which is expressed primarily in the nucleus of somatic cells. CTCF and the protein encoded by this gene are normally expressed in a mutually exclusive pattern that correlates with resetting of methylation marks during male germ cell differentiation. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 140690 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 119 total
• Transcription factor: yes — 13 downstream targets (CollecTRI)
• MANE Select transcript: NM_001386993

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16234
Approved symbol	CTCFL
Name	CCCTC-binding factor like
Location	20q13.31
Locus type	gene with protein product
Status	Approved
Aliases	dJ579F20.2, BORIS, CT27
Ensembl gene	ENSG00000124092
Ensembl biotype	protein_coding
OMIM	607022
Entrez	140690

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 17 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000243914, ENST00000371196, ENST00000422109, ENST00000422869, ENST00000423479, ENST00000426658, ENST00000429804, ENST00000432255, ENST00000433949, ENST00000481655, ENST00000502686, ENST00000539382, ENST00000607923, ENST00000608108, ENST00000608158, ENST00000608263, ENST00000608425, ENST00000608440, ENST00000608720, ENST00000608858, ENST00000608903, ENST00000609232, ENST00000913404

RefSeq mRNA: 21 — MANE Select: NM_001386993 NM_001269040, NM_001269041, NM_001269042, NM_001269043, NM_001269044, NM_001269045, NM_001269046, NM_001269047, NM_001269048, NM_001269049, NM_001269050, NM_001269051, NM_001269052, NM_001269054, NM_001269055, NM_001386993, NM_001386994, NM_001386995, NM_001386996, NM_001386997, NM_080618

CCDS: CCDS13459, CCDS58776, CCDS58777, CCDS58778, CCDS58779, CCDS58780, CCDS58781, CCDS58782, CCDS68161, CCDS68162, CCDS68163, CCDS68164

Canonical transcript exons

ENST00000243914 — 11 exons

Exon	Start	End
ENSE00001182224	57525028	57525140
ENSE00001598190	57514592	57514741
ENSE00001705743	57518758	57518891
ENSE00001785929	57515714	57515834
ENSE00002214930	57523663	57524216
ENSE00003469290	57503436	57503601
ENSE00003475266	57508606	57508788
ENSE00003627580	57512592	57512752
ENSE00003704916	57519207	57519377
ENSE00003705865	57523068	57523278
ENSE00003921518	57497166	57498701

Expression profiles

Bgee: expression breadth broad, 67 present calls, max score 97.34.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9751 / max 196.9881, expressed in 449 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188112	1.2652	76
188109	0.5989	360
188111	0.1110	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.34	gold quality
oocyte	CL:0000023	92.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.03	gold quality
right testis	UBERON:0004534	74.91	gold quality
testis	UBERON:0000473	74.33	gold quality
left testis	UBERON:0004533	73.12	gold quality
adult organism	UBERON:0007023	62.41	gold quality
lower lobe of lung	UBERON:0008949	54.54	silver quality
buccal mucosa cell	CL:0002336	50.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	49.86	silver quality
cortex of kidney	UBERON:0001225	46.66	gold quality
lymph node	UBERON:0000029	46.29	gold quality
blood	UBERON:0000178	45.98	gold quality
epithelium of nasopharynx	UBERON:0001951	45.74	gold quality
colonic epithelium	UBERON:0000397	45.66	gold quality
sural nerve	UBERON:0015488	45.51	gold quality
liver	UBERON:0002107	45.40	silver quality
right lobe of liver	UBERON:0001114	45.24	silver quality
bone marrow cell	CL:0002092	45.12	gold quality
middle temporal gyrus	UBERON:0002771	44.02	gold quality
kidney	UBERON:0002113	43.80	gold quality
bone marrow	UBERON:0002371	43.38	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
adult mammalian kidney	UBERON:0000082	42.07	gold quality
leukocyte	CL:0000738	42.06	gold quality
monocyte	CL:0000576	41.66	gold quality
duodenum	UBERON:0002114	41.57	gold quality
skeletal muscle organ	UBERON:0014892	41.45	gold quality
muscle of leg	UBERON:0001383	41.43	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	11.67
E-ANND-3	yes	5.05
E-MTAB-8060	no	76.58
E-GEOD-83139	no	2.85

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

13 targets.

Target	Regulation
BAG1	Activation
BRCA1
CTAG1B	Activation
CTCFL
FER	Unknown
GAL3ST1
MAGEA4
MYC
NOTCH3
PGR	Activation
PRMT7
RBL2
TBXT

JASPAR motifs

Motif	Name	Family
MA1102.1	CTCFL	More than 3 adjacent zinc fingers
MA1102.2	CTCFL	More than 3 adjacent zinc fingers
MA1102.3	CTCFL	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:26268681

Upstream regulators (CollecTRI, top): CTCFL

miRNA regulators (miRDB)

86 targeting CTCFL, 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-7110-3P	100.00	73.18	2486
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4267	99.96	66.53	2368
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-6772-5P	99.94	67.01	577
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-545-5P	99.66	70.18	2308

Literature-anchored findings (GeneRIF, showing 40)

• Data indicate that reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter mediates epigenetic regulation of this CT gene in lung cancer cells. (PMID:16140944)
• The lack of hypomethylation in the CFCFL promoter reinforces evidence that ‘genome-wide’ hypomethylation is not random. (PMID:16854382)
• BORIS represents a new class of cancer biomarkers different from those currently used in medical practice. (PMID:17062669)
• we detected a high frequency of BORIS expression in uterine cancers. (PMID:17363524)
• The expression of BORIS antigen is much stronger in breast cancer than that in benign breast disease and normal breast tissues, which indicate that BORIS may be involved in the pathogenesis of the breast cancer. (PMID:17428394)
• Activation of BORIS is associated with melanoma (PMID:17957795)
• Alternative promoter usage generated at least five alternatively spliced BORIS mRNAs with different half-lives determined by varying 5’-UTRs. (PMID:17962299)
• These data establish promoter DNA hypomethylation as a mechanism leading to BORIS expression in human ovarian cancer. (PMID:18095639)
• The ability of BORIS to activate promoters of the RP and ER genes points towards possible involvement of BORIS in the establishment, progression and maintenance of breast tumours. (PMID:18195709)
• Chromatin immunoprecipitation analysis of the BAG-1 promoter in DNMT1-overexpressing or DNMT3B-overexpressing colon cells show a permissive chromatin status assoscsiated with DNA binding of BORIS. (PMID:18413740)
• Differential expression of the cancer/testis gene BORIS in human preimplantation development. (PMID:18467432)
• CTCFL/BORIS is a methylation-independent DNA-binding protein that preferentially binds to the paternal H19 differentially methylated region (PMID:18632606)
• BORIS acts as a platform upon which BAT3 and SET1A assemble and exert effects upon chromatin structure and gene expression. (PMID:18765639)
• As no mutations were detected at CTCFL in the patients examined, we conclude that genetic alterations of CTCFL are not responsible for the SRS hypomethylation. (PMID:19675668)
• BORIS (CTCFL) is not expressed in most human breast cell lines and high grade breast carcinomas (PMID:20305816)
• the C-terminal fragment of CTCFL predominantly consists of extended and unordered content. (PMID:20438700)
• Expression of the cancer-germline (CG) (or cancer-testis) antigen gene BORIS/CTCFL has been proposed to mediate activation of CG antigen genes in cancer. (PMID:20649179)
• The short rare alleles of BORIS-MS2 could be used to identify the risk for breast cancer in young patients. (PMID:21034534)
• Data suggest that the BORIS gene is involved in a range of functionally important aspects of both normal gametogenesis and cancer development. (PMID:21079786)
• Data show that the BORIS/CTCF mRNA expression ratio is closely associated with DNA hypomethylation and confers poor prognosis in EOC. (PMID:21296871)
• The activity of CTCF in controlling Rb2/p130 gene expression is impaired by BORIS, which by binding to the Rb2/p130 gene could trigger changes in the chromatin asset established by CTCF affecting CTCF regulatory activity on Rb2/p130 transcription. (PMID:21325284)
• BORIS-MS2 alleles are transmitted through meiosis following Mendelian inheritance, which suggests that this polymorphic minisatellite could be a useful marker for paternity mapping and DNA fingerprinting. (PMID:21495859)
• BORIS positively regulates these CTAs by binding and inducing a shift to a more open chromatin conformation with promoter demethylation (PMID:21558405)
• These findings show that BORIS expression is more widespread than previously believed, and suggest a role for BORIS in nucleolar function. (PMID:21811597)
• a significant up-regulation of BORIS (p<0.001) and TSHZ1 transcripts (p<0.05) for JAs compared to nasal mucosa. (PMID:21874228)
• This review summarizes what is known about BORIS regarding its expression, structure, and function. (PMID:22168535)
• Transcription of the ferT gene in colon cancer cells was found to be driven by an intronic promoter residing in intron 10 of the fer gene and to be regulated by the Brother of the Regulator of Imprinted Sites (BORIS) transcription factor. (PMID:22223638)
• BORIS may be a useful biomarker for prognostic diagnosis of ESCC patients and a potential target for treatment including by BORIS-specific immunotherapy and molecular target therapy. (PMID:22676270)
• down-regulation of endogenous BORIS by specific shRNAs inhibited both RNA transcription and cell cycle progression. The results altogether suggest a role for BORIS in coordinating S phase events with mitosis. (PMID:22724006)
• BORIS induces demethylation of the SBSN CpG island and disruption and activation of chromatin around the SBSN transcription start site, resulting in an increase in SBSN expression. (PMID:22792300)
• our study has shown for the first time that BORIS is expressed in hepatocellular carcinoma (HCC) tissues, and its expression significantly correlates with poor prognosis and cd90 expression. (PMID:23237599)
• The expression of BORIS isoform families in normal ovary (NO) and epithelial ovarian cancer. (PMID:23390377)
• CTCF and BORIS suppressed breast cancer growth; findings provide further evidence that CTCF behaves as a tumor suppressor, and show BORIS has a similar growth inhibitory effect in vitro and in vivo (PMID:23553099)
• Neither the MTHFR polymorphism, nor CTCFL mutations explain a pattern of sperm hypomethylation at paternally imprinting loci (PMID:23955684)
• The ability of BORIS to activate the androgen receptor gene indicates BORIS involvement in the growth and development of prostate tumors. (PMID:24123052)
• BORIS is an RNA-binding protein that associates with polysomes. (PMID:24279897)
• High BORIS transcript variants are associated with laryngeal squamous cell carcinomas. (PMID:24563233)
• CTCFL/BORIS was amongst the top ranked genes differentially expressed between endometrioid and non-endometrioid tumors, and increasing mRNA level of CTCFL/BORIS was highly significantly associated with poor survival. (PMID:24658009)
• The serum levels of MAGE-A and BORIS mRNA, as well as let-7b were significantly higher in patients. (PMID:24983365)
• results provide novel insights into the determinants of NOTCH3 overexpression in cancer cells, by revealing a key role for BORIS as the main mediator of transcriptional deregulation of NOTCH3 (PMID:24984200)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf646	ENSDARG00000061424
danio_rerio	si:dkey-89b17.4	ENSDARG00000075545
danio_rerio	zgc:66472	ENSDARG00000075916
danio_rerio	si:ch211-148l7.4	ENSDARG00000094469
mus_musculus	Ctcfl	ENSMUSG00000070495
rattus_norvegicus	Ctcfl1	ENSRNOG00000028661
drosophila_melanogaster	mld	FBGN0263490

Paralogs (36): ZNF302 (ENSG00000089335), ZNF184 (ENSG00000096654), CTCF (ENSG00000102974), ZNF574 (ENSG00000105732), ZBTB24 (ENSG00000112365), ZNF142 (ENSG00000115568), ZNF473 (ENSG00000142528), ZNF827 (ENSG00000151612), ZNF689 (ENSG00000156853), ZNF208 (ENSG00000160321), ZNF91 (ENSG00000167232), ZNF526 (ENSG00000167625), ZNF764 (ENSG00000169951), ZNF747 (ENSG00000169955), ZNF282 (ENSG00000170265), ZNF160 (ENSG00000170949), ZNF497 (ENSG00000174586), ZBTB34 (ENSG00000177125), ZNF771 (ENSG00000179965), ZNF48 (ENSG00000180035), ZNF594 (ENSG00000180626), ZBTB37 (ENSG00000185278), ZFP92 (ENSG00000189420), ZNF107 (ENSG00000196247), ZNF729 (ENSG00000196350), ZNF569 (ENSG00000196437), ZNF420 (ENSG00000197050), ZNF785 (ENSG00000197162), ZNF665 (ENSG00000197497), ZNF181 (ENSG00000197841), ZNF347 (ENSG00000197937), ZNF84 (ENSG00000198040), ZBTB48 (ENSG00000204859), ZNF845 (ENSG00000213799), ZNF99 (ENSG00000213973), ZNF688 (ENSG00000229809)

Protein

Protein identifiers

Transcriptional repressor CTCFL — Q8NI51 (reviewed: Q8NI51)

Alternative names: Brother of the regulator of imprinted sites, CCCTC-binding factor, CTCF paralog, CTCF-like protein, Cancer/testis antigen 27, Zinc finger protein CTCF-T

All UniProt accessions (5): Q8NI51, F5H2V8, V9GY73, V9GYX4, V9GZ46

UniProt curated annotations — full annotation on UniProt →

Function. Testis-specific DNA binding protein responsible for insulator function, nuclear architecture and transcriptional control, which probably acts by recruiting epigenetic chromatin modifiers. Plays a key role in gene imprinting in male germline, by participating in the establishment of differential methylation at the IGF2/H19 imprinted control region (ICR). Directly binds the unmethylated H19 ICR and recruits the PRMT7 methyltransferase, leading to methylate histone H4 ‘Arg-3’ to form H4R3sme2. This probably leads to recruit de novo DNA methyltransferases at these sites. Seems to act as tumor suppressor. In association with DNMT1 and DNMT3B, involved in activation of BAG1 gene expression by binding to its promoter. Required for dimethylation of H3 lysine 4 (H3K4me2) of MYC and BRCA1 promoters.

Subunit / interactions. Interacts with histones, PRMT7 and SETD1A. Interacts (via N-terminus) with BAG6/BAT3.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Testis specific. Specifically expressed in primary spermatocytes.

Similarity. Belongs to the CTCF zinc-finger protein family.

Isoforms (11)

UniProt ID	Names	Canonical?
Q8NI51-1	1	yes
Q8NI51-2	2
Q8NI51-3	3
Q8NI51-4	4
Q8NI51-5	5
Q8NI51-6	6
Q8NI51-7	7
Q8NI51-8	8
Q8NI51-9	9
Q8NI51-10	10
Q8NI51-11	11

RefSeq proteins (21): NP_001255969, NP_001255970, NP_001255971, NP_001255972, NP_001255973, NP_001255974, NP_001255975, NP_001255976, NP_001255977, NP_001255978, NP_001255979, NP_001255980, NP_001255981, NP_001255983, NP_001255984, NP_001373922, NP_001373923, NP_001373924, NP_001373925, NP_001373926, NP_542185 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (35 total): zinc finger region 11, splice variant 11, compositionally biased region 4, sequence variant 4, region of interest 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NI51-F1	55.75	0.15

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 94 (showing top): TGCGCANK_UNKNOWN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_GENOMIC_IMPRINTING, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_CHROMATIN_REMODELING, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOMF_HISTONE_BINDING, NIKOLSKY_BREAST_CANCER_20Q12_Q13_AMPLICON, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, KOYAMA_SEMA3B_TARGETS_DN, CERIBELLI_PROMOTERS_INACTIVE_AND_BOUND_BY_NFY

GO Biological Process (12): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of gene expression (GO:0010628), protein localization to chromosome (GO:0034502), transcription initiation-coupled chromatin remodeling (GO:0045815), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), establishment of protein localization to chromatin (GO:0071169), genomic imprinting (GO:0071514), chromatin organization (GO:0006325), regulation of DNA-templated transcription (GO:0006355), positive regulation of macromolecule biosynthetic process (GO:0010557), epigenetic regulation of gene expression (GO:0040029)

GO Molecular Function (10): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), zinc ion binding (GO:0008270), histone binding (GO:0042393), chromatin insulator sequence binding (GO:0043035), sequence-specific DNA binding (GO:0043565), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytosol (GO:0005829), nuclear body (GO:0016604), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of gene expression	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
intracellular membraneless organelle	2
gene expression	1
positive regulation of macromolecule biosynthetic process	1
protein localization to organelle	1
transcription initiation at RNA polymerase II promoter	1
positive regulation of gene expression, epigenetic	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
establishment of protein localization to chromosome	1
germ cell development	1
epigenetic programming of gene expression	1
cellular component organization	1
regulation of RNA biosynthetic process	1
macromolecule biosynthetic process	1
positive regulation of biosynthetic process	1
regulation of macromolecule biosynthetic process	1
positive regulation of macromolecule metabolic process	1
chromatin remodeling	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transition metal ion binding	1
protein binding	1
chromatin DNA binding	1
DNA binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

1900 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTCFL	PRMT7	Q9NVM4	857
CTCFL	RAD21	O60216	772
CTCFL	SMC3	Q9UQE7	725
CTCFL	NIPBL	Q6KC79	686
CTCFL	IGF2	P01344	659
CTCFL	CHD8	Q9HCK8	655
CTCFL	COX7A1	P24310	649
CTCFL	WSB1	Q9Y6I7	629
CTCFL	EZH2	Q15910	623
CTCFL	SMC1A	Q14683	623
CTCFL	SIX5	Q8N196	608
CTCFL	STAG2	Q8N3U4	606
CTCFL	SUZ12	Q15022	596
CTCFL	MRPL23	Q16540	588
CTCFL	SETD1A	O15047	577

IntAct

17 interactions, top by confidence:

A	B	Type	Score
FKBP5	CTCFL	psi-mi:“MI:0915”(physical association)	0.400
CTCFL	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
	CTCFL	psi-mi:“MI:0915”(physical association)	0.400
UNC45B	CTCFL	psi-mi:“MI:0915”(physical association)	0.400
CTCFL	NUDC	psi-mi:“MI:0915”(physical association)	0.400
CTCFL	NUDCD3	psi-mi:“MI:0915”(physical association)	0.400
SGTA	CTCFL	psi-mi:“MI:0915”(physical association)	0.400
CTCFL	STIP1	psi-mi:“MI:0915”(physical association)	0.400
STUB1	CTCFL	psi-mi:“MI:0915”(physical association)	0.400
NUDCD2	CTCFL	psi-mi:“MI:0915”(physical association)	0.400
CTCFL	AARSD1	psi-mi:“MI:0915”(physical association)	0.400
CTCFL	ZDHHC17	psi-mi:“MI:0915”(physical association)	0.370
CTCFL	TARS3	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): CTCFL (Two-hybrid), SP1 (Reconstituted Complex), TBP (Reconstituted Complex), CTCFL (Reconstituted Complex), CTCFL (Affinity Capture-MS), CTCFL (Protein-peptide), CTCFL (Affinity Capture-MS), CTCFL (Affinity Capture-MS), NES (Affinity Capture-MS), AKAP9 (Affinity Capture-MS), SETD2 (Affinity Capture-MS), PHKG2 (Affinity Capture-MS), TARSL2 (Affinity Capture-MS), WDR46 (Affinity Capture-MS), RBMXL1 (Affinity Capture-MS)

ESM2 similar proteins: A1L1J6, A2A5K6, A2APF3, D3ZUU2, E9Q8T2, G3V893, G5E8B9, O43167, O70237, O95625, P10074, P22227, P52739, P57071, P98169, Q05516, Q13105, Q1H9T6, Q3B725, Q3B7N9, Q3U288, Q3UH06, Q4VBD9, Q5DU09, Q5EAC5, Q5R633, Q5VTD9, Q60821, Q6DDV0, Q6GL52, Q6NS86, Q6YND2, Q6ZSB9, Q7TS63, Q80X44, Q8BKX7, Q8BXX2, Q8C8V1, Q8CCE9, Q8N1W2

Diamond homologs: A2APF3, P49711, Q08705, Q61164, Q8NI51, Q9R1D1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CTCFL	“up-regulates quantity by expression”	BAG1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 12 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	6	51.7×	5e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	11
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1677 predictions. Top by Δscore:

Variant	Effect	Δscore
20:57503453:T:TA	donor_gain	1.0000
20:57503474:T:TA	donor_gain	1.0000
20:57503495:T:TA	donor_gain	1.0000
20:57512624:TGA:T	donor_gain	1.0000
20:57518688:CA:C	donor_gain	1.0000
20:57518775:TGC:T	donor_gain	1.0000
20:57519204:TACCT:T	donor_loss	1.0000
20:57519205:ACC:A	donor_loss	1.0000
20:57519206:C:T	donor_loss	1.0000
20:57523705:A:AC	donor_gain	1.0000
20:57523706:C:CC	donor_gain	1.0000
20:57503435:CCGT:C	donor_gain	0.9900
20:57503602:C:CC	acceptor_gain	0.9900
20:57508677:T:TA	donor_gain	0.9900
20:57512587:AATAC:A	donor_loss	0.9900
20:57512588:ATAC:A	donor_loss	0.9900
20:57512589:TACCT:T	donor_loss	0.9900
20:57512591:CCTG:C	donor_gain	0.9900
20:57512594:G:A	donor_gain	0.9900
20:57512607:A:C	donor_gain	0.9900
20:57512751:ACCT:A	acceptor_loss	0.9900
20:57512752:CCTAA:C	acceptor_loss	0.9900
20:57512753:C:CA	acceptor_loss	0.9900
20:57514886:C:CA	donor_gain	0.9900
20:57514919:CAG:C	donor_gain	0.9900
20:57515708:CCTTA:C	donor_loss	0.9900
20:57515709:CTTA:C	donor_loss	0.9900
20:57515710:TTA:T	donor_loss	0.9900
20:57515711:TA:T	donor_loss	0.9900
20:57515712:AC:A	donor_loss	0.9900

AlphaMissense

4415 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:57514701:G:C	F407L	1.000
20:57514701:G:T	F407L	1.000
20:57514703:A:G	F407L	1.000
20:57518851:A:C	F322L	1.000
20:57518851:A:T	F322L	1.000
20:57518853:A:G	F322L	1.000
20:57514702:A:G	F407S	0.999
20:57514724:A:G	C400R	0.999
20:57515730:G:C	H388Q	0.999
20:57515730:G:T	H388Q	0.999
20:57515740:A:G	L385P	0.999
20:57515802:G:C	H364Q	0.999
20:57515802:G:T	H364Q	0.999
20:57515814:A:C	H360Q	0.999
20:57515814:A:T	H360Q	0.999
20:57518778:A:G	C347R	0.999
20:57518787:A:G	C344R	0.999
20:57518819:C:G	R333P	0.999
20:57518824:G:C	H331Q	0.999
20:57518824:G:T	H331Q	0.999
20:57518826:G:C	H331D	0.999
20:57518834:A:G	L328P	0.999
20:57518874:A:G	C315R	0.999
20:57519211:G:C	H307Q	0.999
20:57519211:G:T	H307Q	0.999
20:57519223:A:C	H303Q	0.999
20:57519223:A:T	H303Q	0.999
20:57519250:G:C	F294L	0.999
20:57519250:G:T	F294L	0.999
20:57519252:A:G	F294L	0.999

dbSNP variants (sampled 300 via entrez): RS1000057836 (20:57513911 C>T), RS1000230362 (20:57497201 G>A), RS1000244594 (20:57507868 A>T), RS1000314734 (20:57514089 C>A,T), RS1000382292 (20:57520276 C>T), RS1000456458 (20:57519687 T>C), RS1000651502 (20:57512804 C>G,T), RS1000809913 (20:57504199 A>G), RS1000816044 (20:57518767 G>A), RS1000874804 (20:57499689 G>C,T), RS1001117555 (20:57519027 C>A), RS1001283821 (20:57515152 T>C), RS1001316596 (20:57515468 A>C), RS1001712811 (20:57525929 T>C,G), RS1001729450 (20:57515150 T>C)

Disease associations

OMIM: gene MIM:607022 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000635_28	Response to statin therapy	4.000000e-06
GCST001762_902	Obesity-related traits	4.000000e-08
GCST001809_13	Type 2 diabetes	2.000000e-06
GCST002345_2	Response to cytadine analogues (cytosine arabinoside)	8.000000e-06
GCST004639_8	Prudent dietary pattern	2.000000e-06
GCST005993_22	Mean corpuscular hemoglobin	2.000000e-25
GCST006011_60	Mean corpuscular volume	1.000000e-39
GCST010244_320	Triglyceride levels	6.000000e-15
GCST90013406_222	Liver enzyme levels (alkaline phosphatase)	2.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0003940	physical activity
EFO:0008111	diet measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004530	triglyceride measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases mutagenesis, affects methylation, increases methylation	3
Decitabine	affects methylation, increases expression	2
Valproic Acid	affects expression, increases expression	2
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Carbamazepine	affects expression	1
Methapyrilene	increases methylation	1
Cyclosporine	decreases methylation	1
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	1

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A0U4	SEES3-1V human CTCFL, clone1	Embryonic stem cell	Male
CVCL_A0U5	SEES3-1V human CTCFL, clone2	Embryonic stem cell	Male
CVCL_A0U6	SEES3-1V human CTCFL, clone3	Embryonic stem cell	Male
CVCL_C1LX	Hepa1c1c7 BORIS C68	Cancer cell line	Female
CVCL_C1LY	Hepa1c1c7 BORIS sf2	Cancer cell line	Female

Clinical trials (associated diseases)

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