SNX3

Chr 6

sorting nexin 3

Also known as: Grd19, MCOPS8, SDP3

NCBI Gene: 8724ENSG00000112335UniProt: O60493

This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein does not contain a coiled coil region, like most family members. This protein interacts with phosphatidylinositol-3-phosphate, and is involved in protein trafficking. A pseudogene of this gene is present on the sex chromosomes. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

38
ClinVar variants
18
Pathogenic / LP
0.25
pLI score
0
Active trials
Clinical Summary— SNX3
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 17 VUS of 38 total submissions

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.
0.84LOEUF
pLI 0.249
Z-score 1.86
OE 0.27 (0.11–0.84)
Tolerant

Typical tolerance to LoF variation

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.
1.73Z-score
OE missense 0.49 (0.38–0.63)
44 obs / 90.1 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.0.27 (0.11–0.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.49 (0.38–0.63)
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.1.24
0≤1.21.6
LoF obs/exp: 2 / 7.5Missense obs/exp: 44 / 90.1Syn Z: -1.13

ClinVar Variant Classifications

38 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
VUS17
Likely Benign3
18
Pathogenic
17
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
0
0
0
VUS
0
11
6
0
17
Likely Benign
0
0
0
3
3
Benign
0
0
0
0
0
Total01124338

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

View in ClinVar →

Protein Context — Lollipop Plot

SNX3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SNX3-related microphthalmia syndromic

limited
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
SORTING NEXIN 3; SNX3
MIM #605930 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SNX3-retromer requires an evolutionary conserved MON2:DOPEY2:ATP9A complex to mediate Wntless sorting and Wnt secretion.
McGough IJ et al.·Nat Commun
2018
Targeting sorting nexin 3 to treat pulmonary fibrosis by dual modulating Wnt/β-catenin signaling.
Ma D et al.·Cell Death Dis
2026
SNX3 recruits to phagosomes and negatively regulates phagocytosis in dendritic cells.
Chua RY et al.·Immunology
2013
Absence of mutations in NR2E1 and SNX3 in five patients with MMEP (microcephaly, microphthalmia, ectrodactyly, and prognathism) and related phenotypes.
Kumar RA et al.·BMC Med Genet
2007Case report
Classification of subtypes and identification of dysregulated genes in sepsis.
Tong R et al.·Front Cell Infect Microbiol
2023
Sorting nexin 3 (SNX3) is disrupted in a patient with a translocation t(6;13)(q21;q12) and microcephaly, microphthalmia, ectrodactyly, prognathism (MMEP) phenotype.
Vervoort VS et al.·J Med Genet
2002
Sorting nexin 3 (SNX3) is a component of a tubular endosomal network induced by Salmonella and involved in maturation of the Salmonella-containing vacuole.
Braun V et al.·Cell Microbiol
2010
Identification of a family of sorting nexin molecules and characterization of their association with receptors.
Haft CR et al.·Mol Cell Biol
1998
Formation of retromer transport carriers is disrupted by the Parkinson disease-linked Vps35 D620N variant.
Cui Y et al.·Traffic
2021
Biallelic truncating variants in ATP9A cause a novel neurodevelopmental disorder involving postnatal microcephaly and failure to thrive.
Vogt G et al.·J Med Genet
2022
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