SAXO2

Chr 15

stabilizer of axonemal microtubules 2

Also known as: FAM154B

NCBI Gene: 283726 ENSG00000188659 UniProt: Q658L1 OMIM: 621602

The protein is predicted to bind microtubules and localize to the microtubule cytoskeleton, nucleus, and sperm flagellum. Currently, no human diseases have been definitively associated with SAXO2 mutations in published literature. The gene shows very low constraint against loss-of-function variants (pLI near 0), suggesting it may tolerate such changes in the general population.

OMIM ResearchSummary from RefSeq

Predicted to enable microtubule binding activity. Predicted to be active in microtubule cytoskeleton; nucleus; and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.81

Clinical Summary— SAXO2

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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

69 VUS of 82 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?

1.81LOEUF

pLI 0.000

Z-score -0.70

OE 1.22 (0.80–1.81)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.21Z-score

OE missense 1.04 (0.93–1.16)

228 obs / 219.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.22 (0.80–1.81)

0≤0.351.4

Missense OE?1.04 (0.93–1.16)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 14 / 11.5Missense obs/exp: 228 / 219.4Syn Z: 0.28

This gene — mechanism propensity

0.75top 25%

GOF

0.7028th %ile

LOF

0.3551th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

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

82 submitted variants in ClinVar

ClinVar

Classification Summary

VUS69

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	69	69
Likely Benign	5	5
Benign	0	0
Total	74	74

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap SAXO2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →