CGGBP1

Chr 3

CGG triplet repeat binding protein 1

Also known as: CGGBP, p20-CGGBP

NCBI Gene: 8545 ENSG00000163320 UniProt: Q9UFW8 OMIM: 603363

The protein binds to unmethylated CGG trinucleotide repeats and regulates transcription, particularly at the FMR1 promoter, while also contributing to DNA damage repair and telomere protection. Mutations cause autosomal recessive intellectual disability with seizures and microcephaly, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants, suggesting that complete loss of protein function is poorly tolerated.

OMIM ResearchSummary from RefSeq, UniProt

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. [provided by RefSeq, Jul 2017]

OMIM ResearchGenerating clinical summary…

LOEUF 0.53

Clinical Summary— CGGBP1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.

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ClinVar Variants

57 VUS of 69 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.53LOEUF

pLI 0.818

Z-score 2.20

OE 0.00 (0.00–0.53)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.57Z-score

OE missense 0.55 (0.44–0.69)

52 obs / 95.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.53)

0≤0.351.4

Missense OE?0.55 (0.44–0.69)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 0 / 5.6Missense obs/exp: 52 / 95.0Syn Z: -0.95

ClinVar Variant Classifications

69 submitted variants in ClinVar

ClinVar

Classification Summary

VUS57

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	57	57
Likely Benign	1	1
Benign	0	0
Total	58	58

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

8 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap CGGBP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →