CGGBP1

Summary

CGGBP1 (CGG triplet repeat binding protein 1, HGNC:1888) is a protein-coding gene on chromosome 3p11.1, encoding CGG triplet repeat-binding protein 1 (Q9UFW8). Binds to nonmethylated 5’-d(CGG)(n)-3’ trinucleotide repeats in the FMR1 promoter.

This gene encodes a CGG repeat-binding protein that primarily localizes to the nucleus. CGG trinucleotide repeats are implicated in many disorders as they often act as transcription- and translation-regulatory elements, can produce hairpin structures which cause DNA replication errors, and form regions prone to chromosomal breakage. CGG repeats are also targets for CpG methylation. In addition to its ability to bind CGG repeats and regulate transcription, this gene is believed to play a role in DNA damage repair and telomere protection. In vitro studies indicate this protein does not bind to methylated CpG sequences.

Source: NCBI Gene 8545 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 69 total
• Druggable target: yes
• MANE Select transcript: NM_001008390

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1888
Approved symbol	CGGBP1
Name	CGG triplet repeat binding protein 1
Location	3p11.1
Locus type	gene with protein product
Status	Approved
Aliases	p20-CGGBP, CGGBP
Ensembl gene	ENSG00000163320
Ensembl biotype	protein_coding
OMIM	603363
Entrez	8545

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000309534, ENST00000398392, ENST00000462901, ENST00000467332, ENST00000474441, ENST00000482016, ENST00000675130, ENST00000894700, ENST00000913949, ENST00000913951, ENST00000964552

RefSeq mRNA: 3 — MANE Select: NM_001008390 NM_001008390, NM_001195308, NM_003663

CCDS: CCDS43111

Canonical transcript exons

ENST00000482016 — 4 exons

Exon	Start	End
ENSE00001533031	88057191	88057292
ENSE00001533033	88058019	88058223
ENSE00001823242	88058815	88059005
ENSE00001909098	88051950	88055999

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.8188 / max 260.8929, expressed in 1823 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43294	39.0747	1823
43293	1.7051	730
43297	0.8552	485
43296	0.7493	399
43295	0.4345	174

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	97.29	gold quality
visceral pleura	UBERON:0002401	97.27	gold quality
cortical plate	UBERON:0005343	97.23	gold quality
epithelium of nasopharynx	UBERON:0001951	96.92	gold quality
ventricular zone	UBERON:0003053	96.83	gold quality
parietal pleura	UBERON:0002400	96.76	gold quality
pleura	UBERON:0000977	96.70	gold quality
ganglionic eminence	UBERON:0004023	96.64	gold quality
pancreatic ductal cell	CL:0002079	96.54	gold quality
superficial temporal artery	UBERON:0001614	96.37	gold quality
tibia	UBERON:0000979	96.23	gold quality
lymph node	UBERON:0000029	96.19	gold quality
caput epididymis	UBERON:0004358	96.10	gold quality
endometrium	UBERON:0001295	96.01	gold quality
mammary duct	UBERON:0001765	95.92	gold quality
urethra	UBERON:0000057	95.84	gold quality
tonsil	UBERON:0002372	95.81	gold quality
renal medulla	UBERON:0000362	95.77	gold quality
pylorus	UBERON:0001166	95.76	gold quality
cauda epididymis	UBERON:0004360	95.69	gold quality
monocyte	CL:0000576	95.65	gold quality
trabecular bone tissue	UBERON:0002483	95.60	gold quality
skin of hip	UBERON:0001554	95.56	gold quality
cardia of stomach	UBERON:0001162	95.50	gold quality
mononuclear cell	CL:0000842	95.48	gold quality
pericardium	UBERON:0002407	95.46	gold quality
leukocyte	CL:0000738	95.41	gold quality
trigeminal ganglion	UBERON:0001675	95.40	gold quality
esophagus squamous epithelium	UBERON:0006920	95.25	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.94

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
FMR1	Repression

JASPAR motifs

Motif	Name	Family
MA2538.1	CGGBP1

JASPAR matrix evidence (PMIDs): PMID:33561217

Upstream regulators (CollecTRI, top): NFIX

miRNA regulators (miRDB)

259 targeting CGGBP1, 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-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883

Literature-anchored findings (GeneRIF, showing 13)

• CGGBP1 was mapped to chromosome 3p and a sequence of 235 nucleotides 5’ upstream of CGGBP1 is essential for promoter activity. (PMID:14667814)
• Differences in factors implicated in CGG repeat instability–CGG repeat size, XS548/FRAXAC1 haplotypes, and AGG interspersion pattern-are present in the Basque populations analyzed. (PMID:19728537)
• CGGBP-20 downregulates the activity of 5’-region of FMR1 gene in the presence of GCC-triplets only. (PMID:20141036)
• CGGBP1 depletion by RNA interference in tumor-derived cells caused an increase in the cell population at G0/G1 phase and reduced the number of cells in the S phase. (PMID:21733196)
• Our results suggest that CGGBP1 phosphorylation at S164 is a novel telomere protection signal, which can affect telomere-protective function of the shelterin complex (PMID:24196442)
• Over-expression of miR-7 could significantly inhibit the growth of human lung cancer cells in vivo and in vitro, which might be related to the down-regulated expression of tumor growth-associated protein CGGBP1 (PMID:24491049)
• By studying global gene expression patterns and genome-wide DNA-binding patterns of CGGBP1, it has been shown that a possible mechanism through which it affects the expression of RNA Pol II-transcribed genes in trans depends on Alu RNA. (PMID:25483050)
• CGGBP1 is a possible bidirectional regulator of CpG methylation at Alus, and acts as a repressor of methylation at L1 retrotransposons. (PMID:25981527)
• CGGBP1 has no direct effect on FMR1 transcription and CGG repeat stability. (PMID:26306647)
• CGGBP1 protein play an important cytoprotective role in patients with cancer. (PMID:26482656)
• CGGBP1 is a regulator of CTCF-DNA-binding pattern with a direct effect on a potential chromatin barrier like functioning of repeatrich and motif-rich regions. (PMID:31547883)
• CGGBP1-regulated cytosine methylation at CTCF-binding motifs resists stochasticity. (PMID:32727353)
• CGGBP1-dependent CTCF-binding sites restrict ectopic transcription. (PMID:34585631)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cggbp1	ENSMUSG00000054604
rattus_norvegicus	Cggbp1	ENSRNOG00000000718

Protein

Protein identifiers

CGG triplet repeat-binding protein 1 — Q9UFW8 (reviewed: Q9UFW8)

Alternative names: 20 kDa CGG-binding protein, p20-CGGBP DNA-binding protein

All UniProt accessions (2): C9JUJ0, Q9UFW8

UniProt curated annotations — full annotation on UniProt →

Function. Binds to nonmethylated 5’-d(CGG)(n)-3’ trinucleotide repeats in the FMR1 promoter. May play a role in regulating FMR1 promoter.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous. Highly expressed in placenta, thymus, lymph nodes, cerebellum and cerebral cortex. Low expression in other regions of the brain.

Miscellaneous. Binding is severely inhibited by complete or partial cytosine-specific DNA methylation of the binding motif.

RefSeq proteins (3): NP_001008391, NP_001182237, NP_003654 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033375	Cggbp1	Family

UniProt features (5 total): modified residue 2, chain 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UFW8-F1	76.26	0.15

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 (2): 56, 164

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 251 (showing top): RNGTGGGC_UNKNOWN, ENK_UV_RESPONSE_KERATINOCYTE_UP, SP1_Q2_01, ATGTTAA_MIR302C, NFKB_C, BLALOCK_ALZHEIMERS_DISEASE_UP, TGCTGAY_UNKNOWN, KMCATNNWGGA_UNKNOWN, GTGTTGA_MIR505, ZIC1_01, DOUGLAS_BMI1_TARGETS_DN, SANSOM_APC_TARGETS_DN, EGR1_01, GOBP_CHROMATIN_REMODELING, GTGACTT_MIR224

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of gene expression (GO:0010468), epigenetic regulation of gene expression (GO:0040029), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (5): double-stranded DNA binding (GO:0003690), identical protein binding (GO:0042802), DNA-binding transcription factor binding (GO:0140297), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
gene expression	1
regulation of macromolecule biosynthetic process	1
chromatin remodeling	1
regulation of gene expression	1
regulation of DNA-templated transcription	1
DNA binding	1
protein binding	1
transcription factor binding	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

1545 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CGGBP1	FMR1	Q06787	793
CGGBP1	ZNF654	Q8IZM8	619
CGGBP1	C3orf38	Q5JPI3	605
CGGBP1	IQSEC1	Q6DN90	555
CGGBP1	NBEAL2	Q6ZNJ1	546
CGGBP1	GIN1	Q9NXP7	492
CGGBP1	ATXN7L3B	Q96GX2	490
CGGBP1	ZIC4	Q8N9L1	486
CGGBP1	LRRC3B	Q96PB8	476
CGGBP1	URB1	O60287	470
CGGBP1	TMEM209	Q96SK2	450
CGGBP1	CLN8	Q9UBY8	410
CGGBP1	NKIRAS1	Q9NYS0	396
CGGBP1	TMCC3	Q9ULS5	393
CGGBP1	TOPAZ1	Q8N9V7	384

IntAct

102 interactions, top by confidence:

A	B	Type	Score
MRM1	CGGBP1	psi-mi:“MI:0915”(physical association)	0.800
CGGBP1	REL	psi-mi:“MI:0915”(physical association)	0.670
REL	CGGBP1	psi-mi:“MI:0915”(physical association)	0.670
CGGBP1	CGGBP1	psi-mi:“MI:0915”(physical association)	0.670
SPIN1	SPINDOC	psi-mi:“MI:0914”(association)	0.640
SDCBP	CGGBP1	psi-mi:“MI:0915”(physical association)	0.560
GLRX3	CGGBP1	psi-mi:“MI:0915”(physical association)	0.560
FAM124A	CGGBP1	psi-mi:“MI:0915”(physical association)	0.560
CGGBP1	FAM124A	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	CGGBP1	psi-mi:“MI:0915”(physical association)	0.560
BOLA2-SMG1P6	CGGBP1	psi-mi:“MI:0915”(physical association)	0.560
CDKN2D	CGGBP1	psi-mi:“MI:0915”(physical association)	0.560
TXN2	CGGBP1	psi-mi:“MI:0915”(physical association)	0.560
REL	CGGBP1	psi-mi:“MI:0915”(physical association)	0.560
PICK1	CGGBP1	psi-mi:“MI:0915”(physical association)	0.560
CDC37	CGGBP1	psi-mi:“MI:0915”(physical association)	0.560
GORASP2	CGGBP1	psi-mi:“MI:0915”(physical association)	0.560
PIAS2	CGGBP1	psi-mi:“MI:0915”(physical association)	0.560
PAX6	CGGBP1	psi-mi:“MI:0915”(physical association)	0.560
POLR1C	CGGBP1	psi-mi:“MI:0915”(physical association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
SPIN2B	WDHD1	psi-mi:“MI:0914”(association)	0.530

BioGRID (79): CGGBP1 (Two-hybrid), CGGBP1 (Two-hybrid), CGGBP1 (Two-hybrid), GLRX3 (Two-hybrid), FAM124A (Two-hybrid), CGGBP1 (Affinity Capture-MS), CGGBP1 (Affinity Capture-MS), CGGBP1 (Affinity Capture-MS), CGGBP1 (Co-fractionation), CGGBP1 (Co-fractionation), DDB1 (Co-fractionation), CGGBP1 (Two-hybrid), CGGBP1 (Affinity Capture-MS), CGGBP1 (Affinity Capture-MS), CGGBP1 (Affinity Capture-MS)

ESM2 similar proteins: A2PYH4, A2RUV5, A4Z943, A4Z944, B2RD01, D3Z4R1, F1QWA8, O00463, O18475, O60308, O75417, O95786, O96006, P12258, P46063, P49916, P57075, P70191, P97386, Q0V842, Q29RQ5, Q49AG3, Q5MAE6, Q5N870, Q5RF63, Q5SVZ6, Q5SZJ8, Q6AYJ1, Q6PCN7, Q6PFX2, Q6Q899, Q6R2W3, Q7M3K2, Q7X7E9, Q8BHG9, Q8BYH3, Q8CGS6, Q8GT06, Q8N328, Q8R5F7

Diamond homologs: Q8BHG9, Q9UFW8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

819 predictions. Top by Δscore:

Variant	Effect	Δscore
3:88056000:C:CC	acceptor_gain	1.0000
3:88056001:T:C	acceptor_gain	1.0000
3:88056004:C:CT	acceptor_gain	1.0000
3:88058055:G:C	donor_gain	1.0000
3:88058383:C:A	donor_gain	1.0000
3:88055905:C:CT	acceptor_gain	0.9900
3:88055995:TGGTT:T	acceptor_gain	0.9900
3:88055996:GGTT:G	acceptor_gain	0.9900
3:88055997:GTT:G	acceptor_gain	0.9900
3:88056001:T:TC	acceptor_gain	0.9900
3:88056005:A:T	acceptor_gain	0.9900
3:88056009:C:CT	acceptor_gain	0.9900
3:88058054:A:AC	donor_gain	0.9900
3:88058054:AG:A	donor_gain	0.9900
3:88058107:T:A	donor_gain	0.9900
3:88058219:CTTTA:C	acceptor_gain	0.9900
3:88058224:C:CC	acceptor_gain	0.9900
3:88058382:T:TA	donor_gain	0.9900
3:88058397:T:TA	donor_gain	0.9900
3:88058424:T:TA	donor_gain	0.9900
3:88058914:T:TA	donor_gain	0.9900
3:88141049:G:GG	donor_gain	0.9900
3:88056000:C:CA	acceptor_loss	0.9800
3:88056001:T:A	acceptor_loss	0.9800
3:88056010:A:T	acceptor_gain	0.9800
3:88058013:GTTTA:G	donor_loss	0.9800
3:88058014:TTTA:T	donor_loss	0.9800
3:88058015:TTACC:T	donor_loss	0.9800
3:88058016:TA:T	donor_loss	0.9800
3:88058017:A:T	donor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000021226 (3:88072811 A>C,G), RS1000088188 (3:88071515 G>A), RS1000198310 (3:88143149 C>G,T), RS1000255636 (3:88143402 C>T), RS1000296323 (3:88054686 C>T), RS1000302459 (3:88110295 A>G), RS1000429451 (3:88060099 G>A,C), RS1000458099 (3:88073305 CAAAAA>C,CAAAA), RS1000460330 (3:88103599 A>T), RS1000569410 (3:88091998 AATCTT>A), RS1000621905 (3:88099189 T>C), RS1000690018 (3:88097703 G>A), RS1000756065 (3:88061643 A>G), RS1000767204 (3:88104805 C>T), RS1000826514 (3:88149424 G>A,T)

Disease associations

OMIM: gene MIM:603363 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004630_119	Mean corpuscular hemoglobin	3.000000e-10
GCST005830_81	Hand grip strength	9.000000e-09
GCST010989_229	Body size at age 10	5.000000e-15
GCST011122_46	Walking pace	1.000000e-08
GCST90002390_153	Mean corpuscular hemoglobin	4.000000e-23
GCST90002392_194	Mean corpuscular volume	9.000000e-22
GCST90002396_197	Mean reticulocyte volume	6.000000e-13
GCST90002403_547	Red blood cell count	3.000000e-16

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0006941	grip strength measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724774 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	increases abundance, increases expression	1
cobaltous chloride	decreases expression	1
beta-methylcholine	affects expression	1
K 7174	increases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Ethanol	decreases expression, increases abundance, affects cotreatment	1
Arsenic	increases abundance, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Cyclosporine	decreases expression	1
Gold Compounds	decreases expression	1
Uranium Compounds	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	affects cotreatment, decreases expression, increases abundance	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697440	Binding	Inhibition of CGGBP1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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