SNX27

Chr 1AR

sorting nexin 27

Also known as: DADAND, MRT1, MY014

NCBI Gene: 81609 ENSG00000143376 UniProt: Q96L92 OMIM: 611541

The SNX27 protein regulates retrograde transport from endosomes to the plasma membrane, directing the recycling of internalized transmembrane proteins that contain PDZ-binding motifs and preventing their degradation in lysosomes. Mutations cause autosomal recessive intellectual disability with seizures and behavioral abnormalities, typically presenting in early childhood. SNX27 is highly constrained against loss-of-function variants, indicating that proper protein function is essential for normal development.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the sorting nexin family, a diverse group of cytoplasmic and membrane-associated proteins involved in endocytosis of plasma membrane receptors and protein trafficking through these compartments. All members of this protein family contain a phosphoinositide binding domain (PX domain). A highly similar protein in mouse is responsible for the specific recruitment of an isoform of serotonin 5-hydroxytryptamine 4 receptor into early endosomes, suggesting the analogous role for the human protein. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.191 OMIM phenotype

Clinical Summary— SNX27

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

23 unique Pathogenic / Likely Pathogenic· 190 VUS of 485 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 1.000

Z-score 4.98

OE 0.06 (0.02–0.19)

Highly constrained

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

Missense Constraint?

2.17Z-score

OE missense 0.64 (0.56–0.72)

179 obs / 281.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.19)

0≤0.351.4

Missense OE?0.64 (0.56–0.72)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 2 / 32.8Missense obs/exp: 179 / 281.6Syn Z: 1.58

This gene — mechanism propensity

0.4090th %ile

GOF

0.4974th %ile

LOF

0.64top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 83% of P/LP variants are LoF · LOEUF 0.19

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

485 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19

Likely Pathogenic4

VUS190

Likely Benign234

Benign13

Conflicting2

Pathogenic

Likely Pathogenic

190

VUS

234

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	16	2	1	0	19
Likely Pathogenic	3	1	0	0	4
VUS	4	178	8	0	190
Likely Benign	0	6	91	137	234
Benign	0	0	10	3	13
Conflicting	—				2
Total	23	187	110	140	462

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

12 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap SNX27 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →