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 identical protein binding activity and 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, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.57

Clinical Summary— SNX8

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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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

This gene — mechanism propensity

0.6258th %ile

GOF

0.6053th %ile

LOF

0.3164th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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