SSNA1

Chr 9

SS nuclear autoantigen 1

ENSG00000176101 UniProt: O43805 OMIM: 610882

The protein stabilizes and protects microtubules from damage, induces microtubule branching, and is required for axon outgrowth and cell division. Mutations cause autosomal recessive cerebral palsy with spastic quadriplegia and intellectual disability. The gene shows tolerance to loss-of-function variants, suggesting the pathogenic variants may have different effects on protein function.

OMIM ResearchSummary from RefSeq, UniProt

Microtubule-binding protein which stabilizes dynamic microtubules by slowing growth and shrinkage at both plus and minus ends and serves as a sensor of microtubule damage, protecting microtubules from the microtubule-severing enzyme SPAST (PubMed:34970964). Induces microtubule branching which is mediated by the formation of long SSNA1 fibrils which guide microtubule protofilaments to split apart from the mother microtubule and form daughter microtubules (By similarity). Plays a role in axon outgrowth and branching (PubMed:25390646). Required for cell division (PubMed:25390646)

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.83

Clinical Summary— SSNA1

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.83LOEUF

pLI 0.000

Z-score -0.10

OE 1.05 (0.54–1.83)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.60Z-score

OE missense 1.21 (1.01–1.45)

81 obs / 67.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.05 (0.54–1.83)

0≤0.351.4

Missense OE?1.21 (1.01–1.45)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 5 / 4.8Missense obs/exp: 81 / 67.1Syn Z: -0.96

This gene — mechanism propensity

0.77top 25%

GOF

0.5170th %ile

LOF

0.3067th %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.