RARRES2

Chr 7

retinoic acid receptor responder 2

Also known as: HP10433, TIG2

NCBI Gene: 5919ENSG00000106538UniProt: Q99969

This gene encodes a secreted chemotactic protein that initiates chemotaxis via the ChemR23 G protein-coupled seven-transmembrane domain ligand. Expression of this gene is upregulated by the synthetic retinoid tazarotene and occurs in a wide variety of tissues. The active protein has several roles, including that as an adipokine and as an antimicrobial protein with activity against bacteria and fungi. [provided by RefSeq, Nov 2014]

78
ClinVar variants
52
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— RARRES2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 Pathogenic / Likely Pathogenic· 22 VUS of 78 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.72LOEUF
pLI 0.000
Z-score 0.08
OE 0.97 (0.55–1.72)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.38Z-score
OE missense 0.89 (0.74–1.07)
80 obs / 90.3 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.0.97 (0.55–1.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.74–1.07)
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.0.60
0≤1.21.6
LoF obs/exp: 7 / 7.2Missense obs/exp: 80 / 90.3Syn Z: 1.94

ClinVar Variant Classifications

78 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic3
VUS22
Likely Benign2
Benign2
49
Pathogenic
3
Likely Pathogenic
22
VUS
2
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
49
0
49
Likely Pathogenic
0
0
3
0
3
VUS
0
16
6
0
22
Likely Benign
0
2
0
0
2
Benign
0
0
0
2
2
Total01858278

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RARRES2 · 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
RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer.
Li YQ et al.·Mil Med Res
2023
Large-Scale Plasma Proteomics to Profile Pathways and Prognosis of Chronic Pain.
Li ZY et al.·Adv Sci (Weinh)
2025
Common variants of RARRES2 and RETN contribute to susceptibility to hand osteoarthritis and related pain.
Yan S et al.·Biomark Med
2022
Myeloperoxidase Inhibition Reverses Biomarker Profiles Associated With Clinical Outcomes in HFpEF.
Michaëlsson E et al.·JACC Heart Fail
2023
Metabolomic signature and molecular profile of normal and degenerated human intervertebral disc cells.
Francisco V et al.·Spine J
2023
Identifying novel risk targets in inflammatory skin diseases by comprehensive proteome-wide Mendelian randomization study.
Li Y et al.·Postgrad Med J
2025
Developing serum proteomics based prediction models of disease progression in ADPKD.
Aydogan Balaban HÖ et al.·Nat Commun
2025Functional
The role of Chemerin in human diseases.
Yue G et al.·Cytokine
2023Review
Uncovering the molecular networks of ferroptosis in the pathogenesis of type 2 diabetes and its complications: a multi-omics investigation.
Dong C et al.·Mol Med
2024
Predicted plasma proteomics from genetic scores and treatment outcomes in major depression: a meta-analysis.
Oliva V et al.·Eur Neuropsychopharmacol
2025Meta-analysis
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
Knee Osteoarthritis

Dietary Supplementation With Blueberry in OA

ACTIVE NOT RECRUITING
NCT05784545Phase NAUniversity of ExeterStarted 2023-05-22
Blueberry powder supplementMaltodextrin supplementation
Congenital Adrenal Hyperplasia (CAH)

Fertility And Sexual Function In CAH: CALLIOPE

RECRUITING
NCT07099456University of Roma La SapienzaStarted 2024-11-01
Spinal StenosisLigamentum Flavum Hypertrophy

Cytokines, Neuroplasticity Modulators, and Biomarkers in Spinal Canal Stenosis and Endoscopic Decompression

NOT YET RECRUITING
NCT07232836Phase NAPoznan University of Physical EducationStarted 2025-11-17
Endoscopic Spinal Canal Decompression
Polycystic Ovary SyndromeHypothalamic Amenorrhea

Body Fat as Determinant of Female Gonadal Dysfunction

RECRUITING
NCT03841981Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalStarted 2020-01-31
Anthropometric and physical examinationIndirect calorimetry, accelerometer and seven-day dietary recallBiochemical, hormonal and metabolic phenotyping

External Resources

Links to major genomics databases and tools