SNX14

Chr 6AR

sorting nexin 14

Also known as: RGS-PX2, SCAR20

NCBI Gene: 57231 ENSG00000135317 UniProt: Q9Y5W7 OMIM: 616105

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spinocerebellar ataxia, autosomal recessive 20MIM #616354

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · autosomal recessive spinocerebellar ataxia 20 · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.83

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in SNX14?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 78

1,055 rare PASS variants

Rare truncating (LoF)

1 in 450

208 rare PASS variants

Rare synonymous (reference)

1 in 140

400 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SNX14. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 89	1 in 410
South Asian	~43k	1 in 92	1 in 470
Remaining (unassigned)	~30k	1 in 63	1 in 320
European (Finnish)	~27k	1 in 380	1 in 1,100
Admixed American	~22k	1 in 61	1 in 310
African / African American	~21k	1 in 81	1 in 430
East Asian	~20k	1 in 81	1 in 340
Ashkenazi Jewish	~13k	1 in 150	1 in 440
Middle Eastern	~2,884	1 in 78	1 in 580

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 16 of 29 coding exons well covered in gnomAD exomes; exons 2, 5, 6, 7, 9 and 8 more marginal. Genomes: all 29.? see exons ↓