SNX1

Chr 15

sorting nexin 1

Also known as: HsT17379, VPS5

NCBI Gene: 6642 ENSG00000028528 UniProt: Q13596

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 endosomal protein regulates the cell-surface expression of epidermal growth factor receptor. This protein also has a role in sorting protease-activated receptor-1 from early endosomes to lysosomes. This protein may form oligomeric complexes with family members. This gene results in three transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.34

LOEUF· LoF intol.

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Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.34LOEUF

pLI 0.932

Z-score 4.29

OE 0.16 (0.08–0.34)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.80Z-score

OE missense 0.87 (0.79–0.96)

267 obs / 306.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.16 (0.08–0.34)

0≤0.351.4

Missense OE?0.87 (0.79–0.96)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 5 / 30.6Missense obs/exp: 267 / 306.6Syn Z: 0.33

Background carrier burden — how many people carry a rare variant somewhere in SNX1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 86

754 rare PASS variants

Rare truncating (LoF)

1 in 1,800

90 rare PASS variants

Rare synonymous (reference)

1 in 110

292 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SNX1. 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 110	1 in 2,200
South Asian	~43k	1 in 56	1 in 4,600
Remaining (unassigned)	~30k	1 in 83	1 in 3,700
European (Finnish)	~27k	1 in 340	1 in 3,100
Admixed American	~22k	1 in 98	1 in 420
African / African American	~21k	1 in 89	1 in 2,200
East Asian	~20k	1 in 82	≈ 1 in 6,400
Ashkenazi Jewish	~13k	1 in 250	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 150	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓