CXXC1

Chr 18

CXXC finger protein 1

Also known as: 2410002I16Rik, 5830420C16Rik, CFP1, CGBP, HsT2645, PCCX1, PHF18, SPP1

This protein functions as a transcriptional activator that binds specifically to unmethylated CpG DNA motifs and is a component of the SETD1 complex that regulates gene expression during development. Mutations cause neurodevelopmental disorders with intellectual disability, and the gene follows autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to cause significant developmental effects.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
4
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.34
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryCXXC1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.90) — some intolerance to loss-of-function variants.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.34LOEUF
pLI 0.895
Z-score 4.67
OE 0.18 (0.100.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.15Z-score
OE missense 0.58 (0.520.64)
256 obs / 442.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.18 (0.100.34)
00.351.4
Missense OE0.58 (0.520.64)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 7 / 38.1Missense obs/exp: 256 / 442.4Syn Z: -1.14
DN
0.3196th %ile
GOF
0.3094th %ile
LOF
0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.34

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CXXC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.