SNX25

Chr 4

sorting nexin 25

Also known as: LRP2BP-AS1, MSTP043, SBBI31

NCBI Gene: 83891ENSG00000109762UniProt: Q9H3E2

SNX25 encodes a protein that binds phosphatidylinositol and regulates intracellular trafficking, particularly through negative regulation of TGF-beta receptor signaling and receptor degradation. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy with seizures and developmental delays. The gene is highly constrained against loss-of-function variants (LOEUF 0.518), reflecting its critical role in cellular function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
114
P/LP submissions
0%
P/LP missense
0.52
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— SNX25
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
113 unique Pathogenic / Likely Pathogenic· 151 VUS of 308 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
0.52LOEUF
pLI 0.000
Z-score 4.18
OE 0.34 (0.23–0.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.42Z-score
OE missense 0.94 (0.87–1.02)
415 obs / 439.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.23–0.52)
0≤0.351.4
Missense OE0.94 (0.87–1.02)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 16 / 46.9Missense obs/exp: 415 / 439.6Syn Z: 0.47
DN
0.6646th %ile
GOF
0.7029th %ile
LOF
0.2679th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

308 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic103
Likely Pathogenic10
VUS151
Likely Benign12
103
Pathogenic
10
Likely Pathogenic
151
VUS
12
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
103
0
103
Likely Pathogenic
0
0
10
0
10
VUS
0
105
46
0
151
Likely Benign
0
4
6
2
12
Benign
0
0
0
0
0
Total01091652276

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

View in ClinVar →

Protein Context — Lollipop Plot

SNX25 · protein map & ClinVar variants

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

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 1 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