FXR2

Chr 17

FMR1 autosomal homolog 2

Also known as: FMR1L2, FXR2P

NCBI Gene: 9513ENSG00000129245UniProt: P51116

The protein encoded by this gene is a RNA binding protein containing two KH domains and one RCG box, which is similar to FMRP and FXR1. It associates with polyribosomes, predominantly with 60S large ribosomal subunits. This encoded protein may self-associate or interact with FMRP and FXR1. It may have a role in the development of fragile X cognitive disability syndrome. [provided by RefSeq, Jul 2008]

120
ClinVar variants
20
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— FXR2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 95 VUS of 120 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.18LOEUF
pLI 1.000
Z-score 5.58
OE 0.07 (0.03–0.18)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
2.62Z-score
OE missense 0.63 (0.57–0.70)
258 obs / 407.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.07 (0.03–0.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.63 (0.57–0.70)
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.0.96
0≤1.21.6
LoF obs/exp: 3 / 42.0Missense obs/exp: 258 / 407.0Syn Z: 0.42

ClinVar Variant Classifications

120 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic1
VUS95
Likely Benign4
Benign1
19
Pathogenic
1
Likely Pathogenic
95
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
1
0
1
VUS
0
86
9
0
95
Likely Benign
0
2
0
2
4
Benign
0
0
0
1
1
Total088293120

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

View in ClinVar →

Protein Context — Lollipop Plot

FXR2 · 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
The Fragile X Protein Family in Amyotrophic Lateral Sclerosis.
Mueller S et al.·Mol Neurobiol
2023Review
Comparing loss of individual fragile X proteins suggests strong links to cellular senescence and aging.
Menge S et al.·Cell Mol Life Sci
2025
Clinical Significance of Fragile X Syndrome 2 (FXR2) in Breast Cancer.
Alsalmi OA et al.·Genes (Basel)
2025
Expression of FMR1, FXR1, and FXR2 genes in human prenatal tissues.
Agulhon C et al.·J Neuropathol Exp Neurol
1999
Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services.
Roberts JL et al.·Gene
2014
Interactome of FMRP-N-tat therapeutic unveils key interactions for cellular function in Fragile X neurons.
Leguay K et al.·J Biol Chem
2025
Identification of the hub genes in polycystic ovary syndrome based on disease-associated molecule network.
Wu Y et al.·FASEB J
2023
m(6)A-modified circFNDC3B inhibits colorectal cancer stemness and metastasis via RNF41-dependent ASB6 degradation.
Zeng W et al.·Cell Death Dis
2022
Identification of a long non-coding RNA-associated RNP complex regulating metastasis at the translational step.
Gumireddy K et al.·EMBO J
2013
Novel isoforms of the fragile X related protein FXR1P are expressed during myogenesis.
Khandjian EW et al.·Hum Mol Genet
1998
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools