SNX25

Chr 4

sorting nexin 25

Also known as: LRP2BP-AS1, MSTP043, SBBI31

NCBI Gene: 83891 ENSG00000109762 UniProt: Q9H3E2 OMIM: 620961

SNX25 encodes a protein that binds phosphatidylinositol and regulates intracellular trafficking, particularly through negative regulation of TGF-beta receptor signaling and receptor degradation. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy with seizures and developmental delays. The gene is highly constrained against loss-of-function variants (LOEUF 0.518), reflecting its critical role in cellular function.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable phosphatidylinositol binding activity. Involved in negative regulation of transforming growth factor beta receptor signaling pathway and receptor catabolic process. Predicted to be located in endosome membrane. Predicted to be active in endosome. [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

0.52

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.52LOEUF

pLI 0.000

Z-score 4.18

OE 0.34 (0.23–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.42Z-score

OE missense 0.94 (0.87–1.02)

415 obs / 439.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.23–0.52)

0≤0.351.4

Missense OE?0.94 (0.87–1.02)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 16 / 46.9Missense obs/exp: 415 / 439.6Syn Z: 0.47

Background carrier burden — how many people carry a rare variant somewhere in SNX25?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 54

1,104 rare PASS variants

Rare truncating (LoF)

1 in 1,900

126 rare PASS variants

Rare synonymous (reference)

1 in 86

456 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SNX25. 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 61	1 in 2,000
South Asian	~43k	1 in 42	1 in 1,100
Remaining (unassigned)	~30k	1 in 44	1 in 6,000
European (Finnish)	~27k	1 in 170	1 in 2,100
Admixed American	~22k	1 in 62	1 in 1,400
African / African American	~21k	1 in 44	1 in 2,200
East Asian	~20k	1 in 69	1 in 1,200
Ashkenazi Jewish	~13k	1 in 180	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 44	≈ 1 in 1,400

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): 17 of 19 coding exons well covered in gnomAD exomes; exons 1, 2 marginal. Genomes: all 19.? see exons ↓