MXRA5

Chr X

matrix remodeling associated 5

NCBI Gene: 25878ENSG00000101825UniProt: Q9NR99OMIM: 300938

The protein is a matrix-remodeling associated protein containing leucine-rich repeats and immunoglobulin-like domains that exhibits anti-inflammatory and anti-fibrotic properties in kidney tissue by limiting chemokine, fibronectin and collagen expression. Mutations cause autosomal recessive intellectual disability with seizures and language delay. The gene is highly constrained against loss-of-function variants (LOEUF 0.398), indicating intolerance to protein-disrupting changes.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.40
Clinical Summary— MXRA5
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
49 unique Pathogenic / Likely Pathogenic· 157 VUS of 400 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.40LOEUF
pLI 0.043
Z-score 5.12
OE 0.25 (0.17–0.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.73Z-score
OE missense 1.06 (1.01–1.11)
1213 obs / 1143.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.25 (0.17–0.40)
0≤0.351.4
Missense OE1.06 (1.01–1.11)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 14 / 55.0Missense obs/exp: 1213 / 1143.7Syn Z: -0.19
DN
0.7229th %ile
GOF
0.4777th %ile
LOF
0.3549th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic3
VUS157
Likely Benign10
Benign27
46
Pathogenic
3
Likely Pathogenic
157
VUS
10
Likely Benign
27
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
46
0
46
Likely Pathogenic
0
0
3
0
3
VUS
1
148
8
0
157
Likely Benign
0
8
1
1
10
Benign
0
13
0
14
27
Total11695815243

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

View in ClinVar →

Protein Context — Lollipop Plot

MXRA5 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients