ADGRF5

Chr 6

adhesion G protein-coupled receptor F5

ENSG00000069122UniProt: Q8IZF2

Adhesion G protein-coupled receptor (PubMed:28570277). In alveolar type II (ATII or AT2) cells, required for normal lung surfactant homeostasis (PubMed:28570277). Modulation of both surfactant secretion and uptake by ATII cells is mediated by the downstream activation of GNAQ/GNA11 proteins and may be a consequence of increased cortical F-actin assembly induced by ADGRF5 activation (PubMed:28570277). In the kidney, may play a role in the regulation of acid excretion into the primary urine, possibly by regulating the surface expression of V-ATPase proton pump (By similarity). As a receptor for soluble FNDC4 (sFNDC4), required for proper systemic glucose tolerance, specifically sensitizing white adipose tissue to insulin. Also plays a role in sFNDC4-induced decrease of local inflammation in white adipose tissue (PubMed:34016966)

0
ClinVar variants
0
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— ADGRF5
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.40LOEUF
pLI 0.024
Z-score 5.22
OE 0.26 (0.17–0.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.63Z-score
OE missense 0.93 (0.88–0.99)
677 obs / 725.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.26 (0.17–0.40)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.88–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 15 / 57.8Missense obs/exp: 677 / 725.1Syn Z: -0.52

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ADGRF5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Comprehensive proteogenomic characterization of rare kidney tumors.
Li GX et al.·Cell Rep Med
2024
International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors.
Hamann J et al.·Pharmacol Rev
2015Review
ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer.
Xin S et al.·Exp Hematol Oncol
2023
The adhesion-GPCR ADGRF5 fuels breast cancer progression by suppressing the MMP8-mediated antitumorigenic effects.
Wu Y et al.·Cell Death Dis
2024
The clinical relevance of the adhesion G protein-coupled receptor F5 for human diseases and cancers.
Jacenik D et al.·Biochim Biophys Acta Mol Basis Dis
2023Review
Prevention and treatment of peri-implant fibrosis by functionally inhibiting skeletal cells expressing the leptin receptor.
Suhardi VJ et al.·Nat Biomed Eng
2024Functional
Acral Fibrochondromyxoid Tumor: A Clinicopathologic and Molecular Genetic Study of 37 Cases.
Dehner CA et al.·Mod Pathol
2024Cohort
The Expression Pattern of Adhesion G Protein-Coupled Receptor F5 Is Related to Cell Adhesion and Metastatic Pathways in Colorectal Cancer-Comprehensive Study Based on In Silico Analysis.
Kang H et al.·Cells
2022
The adhesion GPCR GPR116/ADGRF5 has a dual function in pancreatic islets regulating somatostatin release and islet development.
Röthe J et al.·Commun Biol
2024
Mendelian randomization of plasma proteomics identifies novel ALS-associated proteins and their GO enrichment and KEGG pathway analyses.
Lu C et al.·BMC Neurol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

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External Resources

Links to major genomics databases and tools