A Multi-Source Profile of ADGRF2P: adhesion G protein-coupled receptor F2, pseudogene as an IDG Orphan G Protein-Coupled Receptor

ADGRF2P (adhesion G protein-coupled receptor F2, pseudogene) is a gene classified within the Illuminating the Druggable Genome (IDG) program as a target. This multi-source profile integrates annotation, regulatory, and functional data from CFDE-tagged resources to characterize its biological context and therapeutic potential. Our analysis reveals 0 PubMed co-mentions. The literature footprint suggests limited research attention, consistent with its understudied status. No curated gene-set annotations were found for this gene in Enrichr libraries. No GSFM functional predictions were available. No regulatory element data were available for this locus. No multi-dataset associations were found.Together, these findings provide a comprehensive baseline for future investigation of ADGRF2P as a druggable target.

Introduction

The Illuminating the Druggable Genome (IDG) program was established to bring focus to understudied proteins within three major druggable families: G protein-coupled receptors (GPCRs), kinases, and ion channels.¹Despite their therapeutic potential, many of these proteins remain poorly characterized in terms of ligand identity, signaling pathways, and disease associations.¹

ADGRF2P is encoded by a gene with Entrez ID N/A (Ensembl: ENSG00000164393). According to MyGeneInfo²: No summary available.

Methods

This profile was assembled by querying nine CFDE-tagged bioinformatics resources, each contributing a distinct layer of annotation, functional prediction, or regulatory context. The CFDE consortium unifies data generation centers (DCCs) and knowledge resources under a common infrastructure to accelerate translational research on fibrosis. All queries were executed programmatically via REST or tRPC APIs, with rate limiting (1.2 s inter-call delay) to respect server constraints. Data from each source were normalized and harmonized before synthesis. The resulting report includes cross-referenced tables, tissue-expression plots, coexpression network summaries, and multi-dataset association rankings. Figures were rendered by matplotlib and seaborn.

Data sources used in this profile:

1. MyGeneInfo (https://mygene.info) for gene annotation, functional summary, and genomic coordinates.²
2. IDG Classification API (https://maayanlab.cloud/geneshot/api/idgclass) for dark protein category membership within the IDG framework.
3. Geneshot (https://maayanlab.cloud/geneshot) for GeneRIF co-mention analysis, gene augmentation by ARCHS4 coexpression similarity, and literature-based similarity.³
4. Gene-Specific Functional Model (GSFM, https://gsfm.maayanlab.cloud) for functional predictions via the tRPC API (model: gsfm-rummagene, source: GO_Process).⁴
5. Enrichr (https://maayanlab.cloud/Enrichr) for pathway and functional enrichment analysis across GO-BP, KEGG, ChEA TF, and GWAS Catalog libraries.⁵
6. CFDE Linked Data Hub (https://ldh.genome.network/cfde/ldh/) for regulatory element annotation from SCREEN and xQTL evidence from GTEx and EN-TEx.
7. ARCHS4 (https://maayanlab.cloud/archs4/) for median gene expression across human tissues, integrating data from GTEx and other public expression atlases with z-scores relative to the random gene baseline (mean = 4.336, std = 3.921).
8. Metabolomics Workbench MetGENE (https://www.metabolomicsworkbench.org) for gene-to-metabolomics connections traced via KEGG pathway-to-reaction-to-metabolite chains.
9. Harmonizome (https://maayanlab.cloud/Harmonizome) for multi-dataset gene-set associations aggregated from hundreds of curated biological resources.⁶

Results

Literature Co-Mention Landscape

A total of 0 PubMed IDs mention ADGRF2P in GeneRIF annotations³.

Literature-Based Gene Similarity

GeneRIF-based similarity identifies genes that share biological context with ADGRF2P in curated gene-relation-inference statements compiled from the biomedical literature³.

No literature-similar genes were identified for ADGRF2P, consistent with its understudied status and sparse GeneRIF annotation.

Regulatory Element Landscape (CFDE Linked Data Hub)

The CFDE Linked Data Hub integrates regulatory element data from SCREEN, GTEx, and EN-TEx to map regulatory elements and quantitative trait loci associated with ADGRF2P. Regulatory elements include enhancers, promoters, and insulators whose activity profiles overlap or target the ADGRF2P locus.

No regulatory elements or xQTL evidence were identified for the ADGRF2P locus, which may reflect incomplete annotation for this genomic region.

Tissue Expression Profile (ARCHS4)

ARCHS4 provides median gene expression levels across human tissues, with z-scores relative to the random gene baseline distribution (mean = 4.336, std = 3.921). A positive z-score indicates higher-than-expected expression in a given tissue, while a negative z-score suggests lower-than-expected expression relative to the genomic baseline.

Top tissues by absolute z-score:

Top 10 tissues ranked by expression z-score for ADGRF2P, derived from ARCHS4 cross-tissue analysis (Source: ARCHS4)

Functional Predictions (GSFM)

The Gene-Specific Functional Model (GSFM) uses a generative AI approach to predict functional annotations for genes⁴. The model (gsfm-rummagene) was queried for GO Biological Process predictions for ADGRF2P, returning predicted terms with associated probabilities, z-scores, and known-annotation status.

No GSFM predictions were returned for ADGRF2P from the GO_Process source.

Metabolomics Connections (Metabolomics Workbench MetGENE)

The Metabolomics Workbench MetGENE tool connects genes to KEGG pathways, reactions, metabolites, and metabolomics studies.

No MetGENE pathway connections were found for ADGRF2P. This is expected for genes without KEGG pathway annotations.

Multi-Dataset Associations (Harmonizome)

The Harmonizome platform aggregates gene associations from hundreds of curated biological datasets⁶.

Gene Annotation Lookup

The Enrichr genemap service was used to identify all curated gene sets and pathway terms that include ADGRF2P. Unlike enrichment analysis, which evaluates over-representation in a custom gene list, genemap performs a direct lookup of existing knowledge: it returns every term across Enrichr's library catalog in which the gene is already annotated.⁵.

No curated gene-set terms containing ADGRF2P were found in the queried Enrichr libraries (GO-BP, KEGG, ChEA, GWAS Catalog). This is consistent with limited annotation for understudied targets.

Discussion

The literature footprint of ADGRF2P consists of 0 PubMed co-mentions, indicating limited research attention. Within the IDG framework, this level of coverage supports its classification as an understudied target¹.

Therapeutic Context

As a member of the protein family family, ADGRF2P represents a potentially druggable target. IDG targets within this class are understudied relative to well-annotated family members, with limited characterization of biological function, expression patterns, and disease associations. The sparse annotation landscape of ADGRF2P complicates therapeutic prioritization. Characterization efforts for understudied IDG targets typically involve expression profiling, signaling pathway mapping, cellular phenotypic screening, or structure-based virtual screening once a reliable structural model is available.

Literature Network Insights

Knowledge Gaps and Priorities

Key priorities for future investigation of ADGRF2P include:

1. Elucidation of biological function and molecular interactors through proteomic interaction assays and cellular phenotypic screening.
2. Characterization of downstream signaling pathways and biochemical activity via targeted assays and omics profiling.
3. Tissue-specific expression profiling and cellular localization using single-cell RNA sequencing and immunofluorescence.
4. Genetic association studies to link ADGRF2P variants to disease phenotypes using GWAS meta-analysis and Mendelian randomization.
5. Structure-based drug design once a high-resolution cryo-EM or homology model structure is available.
6. Multi-omics integration combining transcriptomics, proteomics, and metabolomics to contextualize ADGRF2P within broader pathophysiological networks.

Supplementary Information

This section provides quick-reference summaries and resource links for ADGRF2P. The GSFM model page can be revisited for up-to-date functional predictions as the model is retrained:

GSFM predictions for ADGRF2P: https://gsfm.maayanlab.cloud/gene/ADGRF2P

Data Summary

Key identifiers and annotation counts for ADGRF2P are summarized below.

Data summary for ADGRF2P