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Predicting the Impact of Deleterious Single-Nucleotide Polymorphisms in the p47ING1a Isoform of Human ING1 Gene

Md Oliullah Rafi1, Md Takim Sarker2, Mohammad Ashik Sheikh2

  • 1Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, 2202, Bangladesh, bau.edu.bd.

Genetics Research
|June 20, 2026
PubMed
Abstract

Insights

Six nonsynonymous single-nucleotide polymorphisms (nsSNPs) in the p47ING1a tumor suppressor

Area of Science:

  • Cancer biology
  • Molecular genetics
  • Structural biology

Background:

  • The ING1 tumor suppressor, specifically the p47ING1a isoform, plays a role in cellular senescence.
  • Its function is mediated by the plant homeodomain (PHD) zinc-finger, which interacts with the H3K4me3 histone mark.
  • The impact of mutations within the PHD domain on ING1a's tumor-suppressive activity is not well understood.

Purpose of the Study:

  • To identify and structurally analyze deleterious nonsynonymous single-nucleotide polymorphisms (nsSNPs) in the p47ING1a PHD domain.
  • To evaluate the functional consequences of these nsSNPs on ING1a's tumor suppressor function.

Main Methods:

  • Computational screening of 347 missense nsSNPs using 12 tools.
  • Stability, evolutionary conservation, and structural modeling (AlphaFold3, GalaxyRefine) were assessed.
  • Binding effects, post-translational modifications, and protein interaction networks were analyzed.

Main Results:

  • Six high-priority nsSNPs (C358S, C374G, W378G, F379V, S382L, R400P) were identified within the PHD domain (residues 353-402).
  • All six mutations were predicted to destabilize the p47ING1a protein.
  • These nsSNPs are predicted to disrupt H3K4me3 binding and Sin3A/HDAC complex interactions.

Conclusions:

  • Six nsSNPs in the p47ING1a PHD domain may impair its tumor-suppressor function by affecting protein stability and critical interactions.
  • These findings highlight the importance of the PHD domain in ING1a's function and provide a basis for experimental validation.
  • The study suggests potential therapeutic targets at the PHD-H3K4me3 interface.
Keywords:
H3K4me3ING1PHD zinc fingercancer genomicsin silico analysisnsSNPsp47ING1aplant homeodomainprotein stabilitytumor suppressor

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