SNX14

Chr 6AR

sorting nexin 14

Also known as: RGS-PX2, SCAR20

NCBI Gene: 57231ENSG00000135317UniProt: Q9Y5W7

This gene encodes a member of the sorting nexin family. Members of this family have a phox (PX) phosphoinositide binding domain and are involved in intracellular trafficking. The encoded protein also contains a regulator of G protein signaling (RGS) domain. Regulator of G protein signaling family members are regulatory molecules that act as GTPase activating proteins for G alpha subunits of heterotrimeric G proteins. Alternate splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

Primary Disease Associations & Inheritance

Spinocerebellar ataxia, autosomal recessive 20MIM #616354
AR
413
ClinVar variants
67
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SNX14
🧬
Gene-Disease Validity (ClinGen)
autosomal recessive spinocerebellar ataxia 20 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
67 Pathogenic / Likely Pathogenic· 172 VUS of 413 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.
0.83LOEUF
pLI 0.000
Z-score 2.61
OE 0.62 (0.48–0.83)
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.
1.85Z-score
OE missense 0.76 (0.69–0.83)
350 obs / 461.8 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.0.62 (0.48–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.69–0.83)
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.1.07
0≤1.21.6
LoF obs/exp: 35 / 56.1Missense obs/exp: 350 / 461.8Syn Z: -0.72

ClinVar Variant Classifications

413 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic31
VUS172
Likely Benign114
Benign52
Conflicting8
36
Pathogenic
31
Likely Pathogenic
172
VUS
114
Likely Benign
52
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
1
28
0
36
Likely Pathogenic
17
0
14
0
31
VUS
0
148
22
2
172
Likely Benign
0
2
71
41
114
Benign
1
1
48
2
52
Conflicting
—8
Total2515218345413

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

View in ClinVar →

Protein Context — Lollipop Plot

SNX14 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SNX14-related intellectual disability, macrocephaly and cerebellar hypoplasia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
SORTING NEXIN 14; SNX14
MIM #616105 · *

Spinocerebellar ataxia, autosomal recessive 20

MIM #616354

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy.
Deneubourg C et al.·Autophagy
2022
Altered lipid homeostasis is associated with cerebellar neurodegeneration in SNX14 deficiency.
Zhou Y et al.·JCI Insight
2024
Congenital Disorders of Autophagy: What a Pediatric Neurologist Should Know.
Ebrahimi-Fakhari D·Neuropediatrics
2018Review
Autosomal recessive spinocerebellar ataxia-20 due to a novel SNX14 variant in an Indian girl.
Sait H et al.·Am J Med Genet A
2022Case report
SNX14 mutations affect endoplasmic reticulum-associated neutral lipid metabolism in autosomal recessive spinocerebellar ataxia 20.
Bryant D et al.·Hum Mol Genet
2018
Exploring the Genetic Variations Underlying SNX14-Linked Autosomal Recessive Spinocerebellar Ataxia Type 20: A Case Series of 17 Patients From a Single Center in the Omani Population and Review of Literature.
Al Shamsi B et al.·Am J Med Genet A
2026Review
The role of novel fusion genes in human GIST cell lines derived from imatinib-resistant GIST patients: A therapeutic potential of fusion gene.
Cho WC et al.·Biochem Biophys Res Commun
2020Cohort
De novo microdeletions of chromosome 6q14.1-q14.3 and 6q12.1-q14.1 in two patients with intellectual disability - further delineation of the 6q14 microdeletion syndrome and review of the literature.
Becker K et al.·Eur J Med Genet
2012Review
Autosomal recessive spinocerebellar ataxia 20: Report of a new patient and review of literature.
Shukla A et al.·Eur J Med Genet
2017Case report
Exome Sequencing and Linkage Analysis Identified Novel Candidate Genes in Recessive Intellectual Disability Associated with Ataxia.
Jazayeri R et al.·Arch Iran Med
2015Case report
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