Pilot Projects Investigating Understudied Proteins Associated with Rare Diseases (R03 Clinical Trial Not Allowed)

Pilot Projects Investigating Understudied Proteins Associated with Rare Diseases (R03 Clinical Trial Not Allowed) is sponsored by National Center for Advancing Translational Sciences (NCATS/NIH). This R03 grant supports pilot projects focused on investigating understudied proteins that are associated with rare diseases. The goal is to generate preliminary data for future research.

Clinical trials are not allowed.

PAR-25-122: Pilot Projects Investigating Understudied Proteins Associated with Rare Diseases (R03 Clinical Trial Not Allowed) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Center for Advancing Translational Sciences ( NCATS ) National Institute of Allergy and Infectious Diseases ( NIAID ) National Institute on Deafness and Other Communication Disorders ( NIDCD ) National Institute of Dental and Craniofacial Research ( NIDCR ) National Institute of Mental Health ( NIMH ) National Institute of Neurological Disorders and Funding Opportunity Title Pilot Projects Investigating Understudied Proteins Associated with Rare Diseases (R03 Clinical Trial Not Allowed) March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) 93. 350, 93.

173, 93. 121, 93. 242, 93.

853, 93. 855 Funding Opportunity Purpose The purpose of this notice of funding opportunity (NOFO) is to solicit applications for pilot projects to elucidate a role for understudied proteins in rare disease. Awards will support generation of preliminary data and/or tools around eligible understudied protein(s).

A list of eligible proteins is provided and are members of druggable protein families that have a known association with a rare disease. This NOFO is intended to jumpstart research on understudied proteins that are associated with rare diseases and provide applicants with sufficient funding to perform basic biochemical and/or biological work to further the characterization of understudied proteins within the context of rare disease.

Open Date (Earliest Submission Date) The following table includes NIH standard due dates marked with an asterisk. Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants. gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description The National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH), is transforming the translational science process so that new treatments and cures for disease can be delivered to patients faster, delivering more treatments for all people more quickly.

NCATS strives to develop innovations to reduce, remove or bypass costly and time-consuming bottlenecks in the translational research pipeline in an effort to speed the delivery of new drugs, diagnostics and medical devices to patients. This notice of funding opportunity (NOFO) aims to promote innovative research to increase knowledge of understudied proteins associated with rare diseases.

The submission of small research grant (R03) applications is encouraged from organizations proposing projects leading to a better understanding of eligible proteins listed below within the context of rare disease. Small research (R03) grants provide flexibility for initiating discrete, well-defined projects that realistically can be completed in one year and require only limited levels of funding.

This program supports different types of projects including, but not limited to, the following: Pilot or feasibility studies; Small, self-contained research projects; Development of research methodology; Development of assays to support compound screening projects; and/or Development of human cell or animal based models.

These awards will support generation of preliminary data and tools around eligible understudied protein(s) with the intent of elucidating the function of these proteins in the context of rare disease and obtaining sufficient preliminary data and/or research resources for subsequent grant applications and/or drug discovery projects. These grants are non-renewable.

The human genome has revealed a great deal about the human proteome, though significant portions of the genome remain understudied. Only a subset of expressed proteins demonstrates the requisite properties to serve as targets for the development of therapeutics.

Many bona fide drug targets likely remain to be studied in the Druggable Proteome (DP), which can be defined as the fraction of proteins which have the ability to bind drug-like molecules. The term "drug-like" refers to the physical, biochemical, and pharmacological attributes of small molecule compounds that are generally recognized to be required for efficacious clinical drugs in humans.

While the number of proteins in the DP is upwards of 4,500, the existing clinical pharmacopeia is represented by only a few hundred targets, leaving a huge swath of druggable biology unexploited. The expanded exploration of the relationship between the protein and the rare disease phenotype, or the development of a useful tool or reagent can accelerate research into a previously understudied protein.

Many interesting and critical biological processes and potential therapeutic avenues remain unexplored because an initial catalyzing event (e.g., association with a biologic process or phenotype, creation of tools or reagents for the protein, etc.) has not yet occurred.

The purpose of this NOFO is to spark such catalyzing events through the support of small R03 awards to identify novel drug targets for the treatment of human disease, specifically rare disease. The goal of this specific solicitation is to provide a needed opportunity for the collection of preliminary data around the role of understudied proteins associated with rare diseases.

This NOFO will provide funding to support research that will characterize new targets for treatment of human disease among the understudied proteins of the Druggable Proteome. These projects should be carried out in a short period of time with limited resources as defined by the funding mechanism.

It has been recognized through workshops and publications that understudied proteins become illuminated when (1) there are tools to study the protein (e.g., tools that modulate protein activity) and/or (2) there is biochemical, cellular, or animal model evidence of disease/physiological relevance.

This NOFO was developed to address the need for expanded research and validation experiments on eligible understudied protein(s), with the intent of producing preliminary data to address the lack of biochemical, cellular, or animal model data associated with many understudied proteins.

It is expected that the award will be used to obtain preliminary data and/or research resources for subsequent grant applications and/or drug discovery projects. The NIH supports research on a broad range of diseases that are defined as rare; that is diseases affecting fewer than 200,000 individuals in the United States (per the Rare Disease Act of 2002).

Collectively, there are an estimated 10,000 rare diseases, which cumulatively affect millions of people in the United States. Most are serious or life-threatening, with a disproportionate number of rare diseases affecting children. At this time, effective treatments are available for fewer than 5%.

Pharos has linked over 6,000 proteins to rare diseases, with over 80% of these proteins considered extremely understudied.

For the purposes of this NOFO, eligible proteins are those that have an association with rare disease through data mining of the NCATS Genetic and Rare Diseases Information Center (GARD), are considered understudied (those proteins that lack small molecule binders and/or have limited biological characterization, and have low numbers of associated publications) and are within a protein family that is traditionally considered druggable.

Proteins open for study under this NOFO: AADACL2, ABHD1, ABHD12B, ABHD14A, ABHD14B, ABHD15, ABHD16B, ABHD17B, ABHD17C, ABHD3, ABHD8, ACOXL, AKAP14, ALKBH6, ANAPC4, ANKRD44, ARHGAP23, ARHGAP28, ARHGAP40, ARL10, ARL16, ARL6, ARL9, ASNSD1, ASPHD1, ASPHD2, ATP5EP2, ATP6AP1L, ATP6V0E2, B3GNT4, C11orf54, C2orf88, CA5BP1, CARNMT1, CASP12, CBLC, CDADC1, CERCAM, CES1P1, CHSY3, CMAHP, CNEP1R1, COA1, CYB5RL, DCAKD, DDX31, DDX3Y, DDX51, DDX55, DDX60L, DHRS1, DHRS13, DHRS7B, DHRS7C, DHRSX, DHX57, DMAC2, DPY19L2P1, DPY19L2P2, DPY19L3, DPY19L4, ECHDC2, ECHDC3, EEF1AKMT3, ELFN2, ENDOD1, EPS8L2, ETFBKMT, FAHD2A, FASTKD1, FASTKD3, FAXDC2, FBLL1, FOLH1B, FOXRED2, GAL3ST3, GAL3ST4, GALNT16, GARNL3, GATC, GBA3, GFOD1, GFOD2, GGACT, GGTA1P, GKAP1, GLB1L2, GLB1L3, GLT1D1, GLT8D2, GSTT1, GUCA1C, GUSBP1, GVINP1, GXYLT1, GXYLT2, HACD4, HDHD2, HDHD3, HECTD2, HECTD3, HS3ST6, IRGQ, ISG20L2, JAKMIP2, JAKMIP3, KAZALD1, KIAA1191, L3HYPDH, LONRF1, LONRF2, LONRF3, MANEAL, MBLAC1, MBLAC2, MDH1B, METTL17, METTL21A, METTL22, METTL25, MOB3A, MOB3B, MOB3C, MPPED1, MTHFSD, MYRFL, NAA16, NAA38, NAT16, NAT8B, NKAIN1, NKAIN4, NLGN4Y, NT5DC1, NYAP1, NYAP2, OAZ2, OGFOD3, OVCH1, OVCH2, OXLD1, PCED1A, PCED1B, PCMTD2, PCYOX1L, PGGHG, PHACTR2, PHYHIP, PHYHIPL, PINLYP, PIP4P2, PLA2G4F, PLBD1, PLPP7, PLPPR1, PLPPR2, PM20D2, PMS2P3, POP1, PPIL4, PPIL6, PPP1R16A, PPP1R21, PPP1R35, PPP1R36, PPP1R37, PPP1R3D, PPP1R3E, PPP4R4, PPP5D1, PRORSD1P, PRSS33, PRXL2B, PTAR1, PTPDC1, PTPN20, PUS7L, PUSL1, RAB9B, RALGAPB, RASL10B, RERGL, RFNG, RIMKLA, RNF130, RNF149, RNF182, RPUSD2, RPUSD3, RPUSD4, SAP130, SCRN2, SDR42E1, SPATA5L1, SPHKAP, SPINT3, SRGAP2B, SYDE2, TAF1D, TATDN3, TCAF1, TDH, THNSL1, TIMM10B, TMEM129, TMPRSS11B, TPGS2, TPTE2P1, TREX1, TRIML2, TRMT2B, TRMT44, TRUB2, TSTD1, TSTD2, TTLL11, UGGT2, UGT3A1, UGT3A2, UNKL, USP31, USP54, USP9Y, VAT1L, VCPKMT, VMA21, ZDHHC18, ZDHHC22 ASXL2, BRD8, BRWD1, BRWD3, CHD2, CHD5, CHD6, CHD9, DIDO1, DPF1, DPF3, FXR2, G2E3, GLYR1, GTF3C4, HAT1, HDGFL1, HDGFL3, ING5, INTS12, JADE1, JADE2, JADE3, JMJD1C, KDM3B, KIAA2026, L3MBTL2, MBD5, MBTD1, MLLT6, MPHOSPH8, MSL3, MUM1, PHF10, PHF11, PHF14, PHF2, PHF20L1, PHF21A, PHF21B, PHF23, PHF3, PHF7, PHRF1, PRDM11, PRMT2, PWWP2B, PYGO1, RIOX1, RIOX2, SCML2, SETD5, SETD6, SFMBT2, SHPRH, SMYD4, SMYD5, TAF3, TCF19, TDRD10, TDRD15, TDRD3, TDRD6, TDRD7, TDRD9, TDRKH, TRIM66, UBR7, UTY, ZGPAT, ZMYND8 ADGRA1, ADGRA3, ADGRB2, ADGRB3, ADGRD1, ADGRD2, ADGRE1, ADGRE3, ADGRF1, ADGRF4, ADGRF5, CELSR2, F2RL2, GPR101, GPR107, GPR12, GPR135, GPR137, GPR146, GPR150, GPR153, GPR157, GPR158, GPR160, GPR162, GPR171, GPR173, GPR176, GPR19, GPR22, GPR26, GPR27, GPR31, GPR37L1, GPR62, GPR78, GPR82, GPR85, GPRC5B, GPRC5C, GPRC5D, MAS1L, MRGPRF, NPBWR2, NPY6R, OPN1MW, P2RY8, RGR ASIC4, BEST2, BEST3, CACNA2D3, CACNA2D4, CACNB1, CACNB3, CACNG3, CACNG4, CACNG6, CACNG8, CALHM2, CALHM5, CALHM6, CLCA2, CLCA4, CLCC1, CLCN4, CLCN6, CLIC2, CLIC3, CLIC5, CLIC6, FXYD6, FXYD7, GLRA4, GPR89A, GPR89B, GRID1, KCNE4, KCNJ15, KCNJ18, KCNJ9, KCNK12, KCNK16, KCNK7, KCNMB2, KCNMB4, LRRC55, PKD1L1, PKD1L2, PKD2L2, PLLP, SCN2B, SCN3B, SCN4B, SLC26A1, TMC2, TMC3, TMC4, TMC5, TMEM38A, TMEM38B, TMEM63A, TMEM63B, TMEM63C, TTYH1, TTYH2, TTYH3 ADCK2, ADPGK, AK3, AK6, AK9, ALPK1, ALPK2, BCKDK, CAMKV, EPHA10, ETNK1, ETNK2, FGGY, FN3KRP, GALK2, GK5, GLYCTK, GUCY2F, IDNK, IP6K2, IP6K3, ITPK1, KSR2, LRRK1, MAP3K21, MAP3K4, MAST2, MAST4, MOS, MYO3A, NADK, NADK2, NEK11, NEK3, NIM1K, NME3, NME4, NME5, NME6, NMRK1, NRBP1, NRK, OXSR1, PAN3, PANK4, PDIK1L, PFKFB1, PHKA1, PI4K2A, PIP5K1B, PKDCC, POMK, PRKY, PRPS2, PSKH1, PSKH2, PSTK, RPS6KC1, RPS6KL1, RSKR, SCYL1, SCYL2, SCYL3, STK31, STK32C, STK36, STKLD1, TBCK, TEX14, TP53RK, TTBK1, TTBK2, UCKL1, ULK4, VRK2, VRK3, WNK2 ELK3, FIZ1, GMEB2, HMGXB3, HMGXB4, IKZF5, KDM5D, MIER3, NKX1-1, RCOR3, RFX8, SP140L, SP5, SRY, ST18, TFAP2D, THAP10, THAP12, THAP6, THAP7, TSC22D2, USF3, ZBED2, ZBED4, ZBTB26, ZBTB34, ZBTB37, ZBTB41, ZBTB42, ZBTB43, ZBTB44, ZBTB45, ZBTB47, ZFHX2, ZFP14, ZFP3, ZFP30, ZFP41, ZFP69, ZFY, ZGLP1, ZKSCAN2, ZKSCAN4, ZNF101, ZNF112, ZNF114, ZNF117, ZNF121, ZNF134, ZNF136, ZNF138, ZNF14, ZNF140, ZNF180, ZNF181, ZNF189, ZNF19, ZNF195, ZNF197, ZNF200, ZNF205, ZNF211, ZNF221, ZNF226, ZNF227, ZNF230, ZNF232, ZNF234, ZNF236, ZNF248, ZNF25, ZNF250, ZNF251, ZNF253, ZNF254, ZNF257, ZNF26, ZNF260, ZNF264, ZNF273, ZNF275, ZNF276, ZNF280D, ZNF282, ZNF285, ZNF287, ZNF30, ZNF302, ZNF317, ZNF319, ZNF32, ZNF320, ZNF329, ZNF333, ZNF334, ZNF34, ZNF345, ZNF37A, ZNF383, ZNF394, ZNF396, ZNF397, ZNF404, ZNF415, ZNF416, ZNF419, ZNF429, ZNF43, ZNF430, ZNF431, ZNF432, ZNF440, ZNF441, ZNF442, ZNF444, ZNF445, ZNF446, ZNF449, ZNF45, ZNF468, ZNF480, ZNF486, ZNF487, ZNF491, ZNF492, ZNF493, ZNF497, ZNF500, ZNF502, ZNF507, ZNF510, ZNF512, ZNF513, ZNF514, ZNF519, ZNF526, ZNF527, ZNF528, ZNF529, ZNF532, ZNF540, ZNF548, ZNF550, ZNF551, ZNF552, ZNF554, ZNF555, ZNF556, ZNF557, ZNF558, ZNF559, ZNF560, ZNF561, ZNF562, ZNF566, ZNF567, ZNF57, ZNF570, ZNF571, ZNF572, ZNF573, ZNF577, ZNF581, ZNF585A, ZNF585B, ZNF586, ZNF596, ZNF599, ZNF600, ZNF605, ZNF606, ZNF610, ZNF611, ZNF614, ZNF615, ZNF616, ZNF619, ZNF620, ZNF621, ZNF623, ZNF624, ZNF626, ZNF627, ZNF641, ZNF653, ZNF660, ZNF662, ZNF665, ZNF669, ZNF670, ZNF672, ZNF676, ZNF678, ZNF680, ZNF681, ZNF682, ZNF688, ZNF689, ZNF696, ZNF697, ZNF70, ZNF708, ZNF709, ZNF721, ZNF724, ZNF726, ZNF730, ZNF736, ZNF75A, ZNF75D, ZNF763, ZNF764, ZNF765, ZNF766, ZNF768, ZNF770, ZNF771, ZNF775, ZNF776, ZNF777, ZNF778, ZNF780A, ZNF780B, ZNF781, ZNF782, ZNF785, ZNF786, ZNF789, ZNF791, ZNF793, ZNF8, ZNF808, ZNF814, ZNF816, ZNF821, ZNF823, ZNF829, ZNF83, ZNF835, ZNF836, ZNF837, ZNF844, ZNF846, ZNF879, ZNF880, ZNF891, ZSCAN12, ZSCAN18, ZSCAN2, ZSCAN22, ZSCAN25, ZSCAN29, ZSCAN5A, ZSCAN9, ZXDB, ZXDC ABCA10, ABCA13, ABCA5, ABCA6, ABCA8, ABCA9, ABCB8, ABCC12, ABCD4, ABCF1, ABCF2, ATP10A, ATP10B, ATP10D, ATP11A, ATP11B, ATP11C, ATP13A1, ATP13A3, ATP13A4, ATP13A5, ATP1B4, ATP8A2, ATP8B2, ATP8B4, ATP9A, ATP9B, SLC10A4, SLC10A5, SLC10A7, SLC12A7, SLC12A8, SLC13A3, SLC16A10, SLC16A11, SLC16A12, SLC16A13, SLC16A14, SLC16A5, SLC16A6, SLC16A8, SLC16A9, SLC17A3, SLC17A4, SLC18B1, SLC22A15, SLC22A16, SLC22A17, SLC22A18AS, SLC22A23, SLC23A3, SLC24A2, SLC24A3, SLC24A4, SLC25A14, SLC25A2, SLC25A22, SLC25A23, SLC25A24, SLC25A25, SLC25A26, SLC25A28, SLC25A30, SLC25A32, SLC25A33, SLC25A34, SLC25A35, SLC25A36, SLC25A38, SLC25A39, SLC25A41, SLC25A42, SLC25A43, SLC25A44, SLC25A45, SLC25A46, SLC25A48, SLC25A53, SLC26A11, SLC26A7, SLC26A8, SLC26A9, SLC27A3, SLC2A10, SLC2A11, SLC2A13, SLC2A4RG, SLC2A6, SLC30A4, SLC30A5, SLC30A6, SLC30A7, SLC30A9, SLC35A5, SLC35B1, SLC35B3, SLC35B4, SLC35C1, SLC35C2, SLC35D1, SLC35D2, SLC35D3, SLC35E1, SLC35E2A, SLC35E2B, SLC35E4, SLC35F1, SLC35F2, SLC35F3, SLC35F4, SLC35F5, SLC35G2, SLC35G3, SLC35G6, SLC36A1, SLC37A1, SLC37A2, SLC38A10, SLC38A11, SLC38A6, SLC38A7, SLC38A9, SLC39A10, SLC39A11, SLC39A12, SLC39A13, SLC39A3, SLC39A5, SLC39A9, SLC41A2, SLC41A3, SLC43A1, SLC43A2, SLC43A3, SLC44A3, SLC44A5, SLC45A1, SLC45A4, SLC46A2, SLC46A3, SLC48A1, SLC4A1AP, SLC4A2, SLC4A3, SLC50A1, SLC51B, SLC52A1, SLC5A12, SLC5A9, SLC6A14, SLC6A15, SLC6A16, SLC6A17, SLC6A18, SLC7A10, SLC7A14, SLC7A6, SLC7A8, SLC9A7, SLC9A9, SLC9B2, SLCO3A1, SLCO5A1 This NOFO accepts different types of projects with the intent of generating preliminary and/or validation data including, but not limited to, the following: Isolation and purification of understudied proteins and initial in vitro characterization; Characterization of cell- and tissue-specific protein expression, localization, and function of understudied protein(s) in native environments; Verification or placement of understudied protein(s) in signaling cascades, including upstream signals and downstream activities; Pre-clinical animal studies of understudied proteins that help to illuminate the role of an understudied protein in the context of human disease; Use of novel tools to validate preliminary disease or physiological associations with understudied proteins in animal models, biomimetic systems, or ex vivo human samples; Development of accessory reagents (e.g., antibodies, peptide fragments, labeled versions of the protein, etc.) for use in downstream studies to generate preliminary data; Assay development, optimization, and validation with the intent of using these assays for further study of selected understudied protein(s); Use of data mining and experimental validation to analyze public data resources to identify and study protein-protein interaction networks or generate hypotheses about the function of understudied protein(s); Studies to identify endogenous ligands for understudied proteins that could lead to study of preliminary structure-activity-relationships (SAR); Structure determination or preparation of understudied proteins for structure determination and characterization by x-ray crystallography, cryo-electron microscopy, or similar approaches.

This NOFO encourages the development and/or use of non-animal methodologies (NAMs) for exploring understudied proteins in rare diseases. Proposed NAMs can include combinations of new and established technologies and methods that are used to replace traditional animal testing, such as tissue chips.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Early-stage investigators are encouraged to apply.

This NOFO is intended to jump start research on understudied proteins that are associated with rare diseases and provide applicants with funding to perform basic biochemical and/or biological work to further the characterization of understudied proteins associated with rare disease. The proposed project must focus on one or more of the eligible proteins listed above.

Preliminary data are not required, and appropriate justification for the proposed approach can be provided through literature citations, data from other sources, or from investigator-generated data if any are available. The project should address critical barriers to understanding the role of understudied proteins in fundamental physiology, in disease processes, and/or as novel therapeutic agents.

Rare Disease Identification - The proposed project must also be focused within the primary context of a rare disease. A list of rare diseases can be found in the NCATS GARD database ( https://rarediseases. info.

nih. gov/ ) or the NORD database, among others.

If the disease is not listed in either of these databases, a rare disease may be identified by one or more references confirming that the prevalence of the disease/condition is 200,000 or fewer patients in the U.S. The following will be considered non-responsive and will not be reviewed: Projects that meet the NIH definition of a clinical trial; Projects where the majority of the proposed work focuses on proteins outside of those featured on the above lists; Applications that propose clinical drug development studies for understudied protein(s); Applications not studying a rare disease (200,000 or fewer patients in the U.S.).

See Section VIII. Other Information for award authorities and regulations. Section II.

Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Not Allowed: Only accepting applications that do not propose clinical trials. Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Application budgets are limited to $100,000 in direct costs (excluding subcontract F&A) for one year and need to reflect the actual needs of the proposed project. The maximum project period for an application submitted under this NOFO is 1 year. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registrations; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply - Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed.

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: This NOFO is intended to jump start research on understudied proteins that are associated with rare diseases and provide applicants with funding to perform basic biochemical and/or biological work to further the characterization of understudied proteins in the context of rare disease.

The proposed project must focus on one or more of the eligible proteins listed above. Preliminary data are not required, and appropriate justification for the proposed approach can be provided through literature citations, data from other sources, or from investigator-generated data if any are available.

The project should address critical barriers to understanding the role of understudied proteins in fundamental physiology, in disease processes, and/or as novel therapeutic agents. Proteins not listed above as eligible for study under this NOFO may only be used in projects proposed for this NOFO as controls for experiments involving eligible proteins from the approved list and shall not be the focus of experimental work.

Evidence Supporting Rare Disease Classification – The Significance section of the Research Strategy must include a section providing evidence supporting rare disease classification. A list of rare diseases can be found in the NCATS GARD database ( https://rarediseases. info.

nih. gov/ ) or the NORD database, among others. If the disease is not listed in either of these databases, a rare disease may be identified by one or more references confirming that the prevalence of the disease/condition that is the primary focus of the research application is 200,000 or fewer patients in the U.S. If the disease/condition has been granted orphan status by the FDA, provide this information in this paragraph.

If the application does not include this information, then it will be considered non-responsive and will not be reviewed.

Biological Rationale - The Research Strategy section should include a background section that clearly outlines the biological rationale for the application, including: 1) a description of the biological rationale linking the understudied target and the rare disease of interest and 2) a description of how this work might move research on rare disease forward.

Future Directions – The Future Directions section should include a short summary of plans after the completion of this project and how this work will lead to future studies around the protein(s) of interest in the context of rare disease. Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions: All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions: If you answered “Yes” to the question “Are Human Subjects Involved?

” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the How to Apply- Application Guide must be followed.

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply- Application Guide must be followed. PHS Assignment Request Form All instructions in the How to Apply- Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM) See Part 2. Section III.

1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants. gov 4. Submission Dates and Times Part I.

contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants. gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in