SNX8

Chr 7

sorting nexin 8

Also known as: Mvp1

NCBI Gene: 29886 ENSG00000106266 UniProt: Q9Y5X2 OMIM: 614905

SNX8 encodes a protein that facilitates intracellular protein transport from early endosomes to the trans-Golgi network through phosphatidylinositol binding and participation in the retromer complex. Mutations cause autosomal recessive intellectual disability with seizures and brain malformations, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.57), suggesting some tolerance to protein disruption.

OMIM ResearchSummary from RefSeq, UniProt

Enables phosphatidylinositol binding activity. Involved in early endosome to Golgi transport and intracellular protein transport. Located in early endosome membrane and retromer complex. [provided by Alliance of Genome Resources, Jun 2026]

OMIM 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)

—

P/LP submissions

—

P/LP missense

0.57

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.062

Z-score 3.00

OE 0.29 (0.16–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.28Z-score

OE missense 0.95 (0.86–1.05)

262 obs / 275.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.16–0.57)

0≤0.351.4

Missense OE?0.95 (0.86–1.05)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 6 / 20.8Missense obs/exp: 262 / 275.2Syn Z: -1.63

Background carrier burden — how many people carry a rare variant somewhere in SNX8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

745 rare PASS variants

Rare truncating (LoF)

1 in 2,000

75 rare PASS variants

Rare synonymous (reference)

1 in 120

349 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SNX8. 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 140	1 in 2,000
South Asian	~43k	1 in 74	1 in 1,200
Remaining (unassigned)	~30k	1 in 110	1 in 1,300
European (Finnish)	~27k	1 in 230	1 in 4,400
Admixed American	~22k	1 in 68	1 in 3,500
African / African American	~21k	1 in 54	1 in 1,800
East Asian	~20k	1 in 100	1 in 3,900
Ashkenazi Jewish	~13k	1 in 230	none seen
Middle Eastern	~2,884	1 in 66	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): 10 of 11 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 11.? see exons ↓