SNX10

Chr 7AR

sorting nexin 10

Also known as: OPTB8

NCBI Gene: 29887 ENSG00000086300 UniProt: Q9Y5X0 OMIM: 614780

This gene encodes a phosphoinositide-binding protein that regulates protein sorting and membrane trafficking in endosomes, and is required for cilium biogenesis and osteoclast differentiation. SNX10 mutations cause autosomal recessive osteopetrosis, a bone disorder characterized by defective bone resorption leading to increased bone density and fractures. The gene shows low constraint against loss-of-function variants (high LOEUF score), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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 protein does not contain a coiled coil region, like some family members. This gene may play a role in regulating endosome homeostasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

OMIM ResearchGenerating clinical summary…

GOFmechanismARLOEUF 1.661 OMIM phenotype

Clinical Summary— SNX10

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Gene-Disease Validity (ClinGen)

autosomal recessive osteopetrosis 8 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

23 unique Pathogenic / Likely Pathogenic· 67 VUS of 168 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.66LOEUF

pLI 0.000

Z-score -0.25

OE 1.07 (0.71–1.66)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.55Z-score

OE missense 0.85 (0.72–1.01)

95 obs / 111.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.07 (0.71–1.66)

0≤0.351.4

Missense OE?0.85 (0.72–1.01)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 14 / 13.0Missense obs/exp: 95 / 111.2Syn Z: 0.54

This gene — mechanism propensity

0.5870th %ile

GOF

0.6345th %ile

LOF

0.3163th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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.

ClinVar Variant Classifications

168 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12

Likely Pathogenic11

VUS67

Likely Benign60

Benign15

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	1	1	0	12
Likely Pathogenic	9	1	1	0	11
VUS	3	58	6	0	67
Likely Benign	0	1	32	27	60
Benign	0	1	11	3	15
Conflicting	—				1
Total	22	62	51	30	166

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

View in ClinVar →

31 pathogenic / likely-pathogenic (of 39) ClinVar copy-number / structural variants overlap SNX10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →