Screening and Functional Validation of Genomic Variants Associated with Human Congenital Anomalies (R01 Clinical Trial Not Allowed) | PAR 25 185

Opportunity Information: Apply for PAR 25 185

The National Institutes of Health (NIH) is offering an R01 research grant opportunity titled "Screening and Functional Validation of Genomic Variants Associated with Human Congenital Anomalies (Clinical Trial Not Allowed)" (Funding Opportunity Number PAR-25-185). The central goal is to help the research community move beyond simply listing DNA sequence variants found in children with congenital conditions and toward determining which variants actually change biology in ways that contribute to disease. In practice, this means supporting projects that can sort through candidate variants tied to human congenital anomalies (HCAs), intellectual and developmental disabilities (IDDs), and inborn errors of metabolism (IEMs), then experimentally validate and characterize their functional consequences.

A major driver behind this announcement is the growing volume of pediatric genomic data already available through widely used, public-facing or controlled-access resources. The opportunity points directly to repositories such as the Database of Genotypes and Phenotypes (dbGaP), the Gabriella Miller Kids First Data Resource Portal, the European Genome-Phenome Archive, and ClinGen, reflecting the expectation that applicants will leverage existing cohorts and variant datasets rather than starting from scratch. NIH is aiming to close a persistent gap in the field: many studies can identify potentially relevant variants through sequencing, but far fewer can demonstrate how those variants affect gene function, developmental pathways, and observable phenotypes.

The work encouraged under this funding opportunity includes variant screening, functional validation, and deeper mechanistic characterization using a range of complementary methods. Applicants can use in silico approaches (for example, computational prediction and prioritization), in vitro systems (such as cell-based assays and organoid models, where appropriate), suitable animal models, or multi-pronged strategies that combine several of these tools to build a convincing functional case. The emphasis is on establishing whether and how a specific genomic change alters biological function in a way that plausibly explains a congenital anomaly-related phenotype. Because the notice explicitly states "Clinical Trial Not Allowed," proposed projects must be non-clinical-trial research; the intent is discovery and functional biology rather than testing clinical interventions in human participants.

This is a discretionary grant under the NIH R01 mechanism within the Health, Income Security and Social Services activity category, with CFDA numbers listed as 93.121, 93.351, and 93.865. The opportunity is open broadly across many organization types, including state, local, and tribal governments; public and private institutions of higher education; independent school districts; special district governments; public housing authorities/Indian housing authorities; nonprofits (with and without 501(c)(3) status); for-profit organizations other than small businesses; and small businesses. The eligible applicant list also explicitly includes a wide range of mission- and community-focused organizations and institution types, such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), faith-based or community-based organizations, U.S. territories or possessions, and certain non-U.S. (foreign) entities and regional organizations. This breadth signals an intent to encourage participation from diverse institutions and research environments, including those serving underrepresented populations and those outside the continental United States.

Key dates and administrative details included in the listing show a creation date of October 30, 2024, and an original closing date of January 7, 2028, indicating a multi-year window in which NIH expects to receive applications under this program announcement. An award ceiling and expected number of awards are not specified in the provided source text. Overall, the opportunity is designed for research teams positioned to take variant candidates emerging from large genomic datasets and deliver credible functional evidence, helping the field distinguish true disease-contributing variants from the many findings that remain ambiguous after sequencing alone.

• The National Institutes of Health in the health, income security and social services sector is offering a public funding opportunity titled "Screening and Functional Validation of Genomic Variants Associated with Human Congenital Anomalies (R01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.121, 93.351, 93.865.
• This funding opportunity was created on 2024-10-30.
• Applicants must submit their applications by 2028-01-07.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 25 185

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: