medRxiv : the preprint server for health sciences · 2026

Gene Portals: A Framework for Integrating Clinical, Functional, and Structural Evidence into Rare Disease Variant Classification.

СтатьяПрепринтНазвание и аннотация: Перевод пока не подготовлен

Обработка статьи · этапы, ошибки и управление

Загрузка состояния…

История · было → стало

Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.

Brünger Tobias, Krey Ilona, Kim Suyeon, Klöckner Chiara, Myers Scott J, Johannesen Katrine M, Stefanski Arthur, Taylor Gary, Perez-Palma Eduardo, Macnee Marie, Schorge Stephanie, Dahl Rebekka S, Yuan Hongjie, Perszyk Riley E, Kim Sukhan, Bajaj Sunanjay, Helbig Ingo, Pan Jen Q, Farrant Mark, Wollmuth Lonnie, Wyllie David J A, Kurganov Erkin, Baez David, Zuberi Sameer, Boßelmann Christian M, Lerche Holger, Mantegazza Massimo, Cestèle Sandrine, May Patrick, Ivaniuk Alina, Meskis Mary Anne, Hood Veronica, Schust Leah, Goodspeed Kimberly, Kang Jing-Qiong, Freed Amber, Gati Cornelius, Montanucci Ludovica, Wuster Arthur, Trinidad Marena, Froelich Steven, Deng Alexander T, Serrano Ángel Aledo, Borovikov Artem, Sharkov Artem, Bouman Arjan, Hajianpour M J, Pal Deb K, Danvoye Leslie, Lederer Damien, Balci Tugce R, Hagebeuk Eveline E O, Heidlebaugh Alexis, Oetjens Kathryn, Hoffman Trevor L, Striano Pasquale, Williams Sarah Drewes, van Engelen Kalene, Howell Katherine B, Khoury Jean, Benke Tim A, Strehlow Vincent, Platzer Konrad, Ramsey Amy, Manaster Lisa, Malepati Sunitha, Fox Pangkong, Noebels Jeffrey, Chung Wendy, Poduri Annapurna, Stripe Laina Lusk, Ruggiero Sarah M, Cohen Stacey, Smith Lacey, Boesch Sylvia, Wilmarth Olivia, Prentice Anna Jenne, Cha Esther, Budnik Nikita, Hommersom Marina P, Kramer Audra, Vanoye Carlos G, Zhang Guo-Qiang, Nothnagel Michael, Palotie Aarno, Daly Mark J, George Alfred L, Zarate Yuri A, Brunklaus Andreas, Traynelis Stephen F, Møller Rikke S, Lemke Johannes R, Lal Dennis

Аннотация

Rare Mendelian disorders affect 300-400 million people globally. Although genetic testing has become widely adopted, gene-specific evidence for tailored variant interpretation remains scattered across resources. We present Gene Portals, a framework for gene-centered multimodal knowledge bases that co-localize expert-harmonized clinical data, functional assays, population variation, structural annotations and gene-specific ACMG/AMP specifications within a single resource. A modular interface integrates this unified evidence with VCEP-refined ACMG specifications to enable automated gene-specific variant classification, infer molecular mechanisms, and support cross-gene analyses. We demonstrate the framework's utility across five Gene portals spanning eleven neurodevelopmental disorder-associated genes, integrating data from 4,423 individuals with 2,838 unique variants, 36,149 ClinVar submissions, and 1,044 expert-curated molecular readouts. By organizing evidence that is otherwise dispersed across multiple sources into a unified, queryable framework, the SCN, GRIN, CACNA1A, SATB2 and SLC6A1 Gene Portals became widely used community resources and provide an extensible template for standardized rare-disease variant interpretation and mechanism-aware discovery.

Gene Portals: A Framework for Integrating Clinical, Functional, and Structural Evidence into Rare Disease Variant Classification.

Ошибки и ограничения

Аннотация