{
  "abstract": "Interpreting membrane protein variation requires connecting clinical evidence to the membrane environments and molecular interactions that govern protein functions. Here, we introduce memVar (https://memvar.sunnylab.org), an integrated database of 10,906,688unique single-nucleotide variants from ClinVar, COSMIC, and gnomAD across 7,732 human membrane-associated proteins. memVar reconciles genomic, transcript, and protein coordinates to link variants with membrane topology, bilayer depth, lipid contacts, functional sites, partner-specific interaction interfaces, and variant-effect predictions, alongside disease, tissue-expression and regulatory annotations. Coordinated sequence, structure and variant views retain source provenance and distinguish clinical assertions, experimental observations, and computational predictions. Our analysis reveals that pathogenic/likely pathogenic missense substitutions are enriched in transmembrane segments and predicted protein-protein interaction sites relative to benign/likely benign substitutions, with pooled odds ratios of 2.47 and 6.67, respectively. IntAct-derived interaction loss or decrease was experimentally recorded for 57.9% of pathogenic/likely pathogenic substitutions versus 7.4% of benign/likely benign substitutions. CFTR examples contextualize the established G551D gating defect and prioritize W202R, a variant of uncertain significance, for tests of protein maturation, surface abundance and channel activity. By connecting variant records to specific molecular questions, memVar potentially supports mechanism-oriented investigation and prioritization of functional experiments.",
  "abstract_shown": true,
  "affiliations": [
    "Hong Kong University of Science and Technology (Guangzhou)"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "Y. Xu"
    },
    {
      "name": "S. HUANG"
    },
    {
      "name": "J. Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Sun"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c50jn78h9j07z.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.04.764121",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764121v1.full",
  "id": "c50jn78h9j07z",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764121v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764121v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c50jn78h9j07z.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:20:43Z",
      "native_id": "10.64898/2026.11.04.764121",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764121v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "memVar: an integrated resource for interpreting human membrane protein variation in molecular and disease contexts",
  "title_text": "memVar: an integrated resource for interpreting human membrane protein variation in molecular and disease contexts",
  "type": "preprint",
  "updated_at": "2026-11-07T00:20:58Z",
  "url": "https://research.draconitic.com/paper/c50jn78h9j07z",
  "venue": "bioRxiv",
  "versions": []
}