SNX14

Chr 6

sorting nexin 14

Also known as: RGS-PX2, SCAR20

NCBI Gene: 57231 ENSG00000135317 UniProt: Q9Y5W7

This protein maintains normal neuronal excitability and synaptic transmission through intracellular trafficking functions, specifically binding phosphatidylinositol 3,5-bisphosphate and mediating autophagosome clearance by facilitating lysosome-autophagosome fusion. Mutations cause spinocerebellar ataxia, autosomal recessive 20 through an autosomal recessive inheritance pattern. The pathogenic mechanism is predicted to involve gain-of-function effects.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.83

Clinical Summary— SNX14

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Gene-Disease Validity (ClinGen)

autosomal recessive spinocerebellar ataxia 20 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

50 unique Pathogenic / Likely Pathogenic· 164 VUS of 425 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.83LOEUF

pLI 0.000

Z-score 2.61

OE 0.62 (0.48–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.85Z-score

OE missense 0.76 (0.69–0.83)

350 obs / 461.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.48–0.83)

0≤0.351.4

Missense OE?0.76 (0.69–0.83)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 35 / 56.1Missense obs/exp: 350 / 461.8Syn Z: -0.72

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSNX14-related intellectual disability, macrocephaly and cerebellar hypoplasiaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6746th %ile

GOF

0.7126th %ile

LOF

0.2969th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

425 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic29

VUS164

Likely Benign115

Benign52

Conflicting8

Pathogenic

Likely Pathogenic

164

VUS

115

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	17	1	3	0	21
Likely Pathogenic	26	0	3	0	29
VUS	0	151	11	2	164
Likely Benign	0	2	72	41	115
Benign	1	1	48	2	52
Conflicting	—				8
Total	44	155	137	45	389

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap SNX14 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →