SPTBN2

Chr 11

spectrin beta, non-erythrocytic 2

Also known as: GTRAP41, SCA5, SCAR14

NCBI Gene: 6712ENSG00000173898UniProt: O15020

Spectrins are principle components of a cell's membrane-cytoskeleton and are composed of two alpha and two beta spectrin subunits. The protein encoded by this gene (SPTBN2), is called spectrin beta non-erythrocytic 2 or beta-III spectrin. It is related to, but distinct from, the beta-II spectrin gene which is also known as spectrin beta non-erythrocytic 1 (SPTBN1). SPTBN2 regulates the glutamate signaling pathway by stabilizing the glutamate transporter EAAT4 at the surface of the plasma membrane. Mutations in this gene cause a form of spinocerebellar ataxia, SCA5, that is characterized by neurodegeneration, progressive locomotor incoordination, dysarthria, and uncoordinated eye movements. [provided by RefSeq, Dec 2009]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpinocerebellar ataxia 5
UniProtSpinocerebellar ataxia, autosomal recessive, 14

Clinical highlights

Gene-disease validity (ClinGen)
spinocerebellar ataxia type 5 · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
12
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.36
LOEUF
Multiple*
Mechanism· G2P
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GeneReview available — SPTBN2
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.36LOEUF
pLI 0.000
Z-score 7.64
OE 0.27 (0.20–0.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
2.63Z-score
OE missense 0.81 (0.77–0.85)
1209 obs / 1495.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.27 (0.20–0.36)
0≤0.351.4
Missense OE?0.81 (0.77–0.85)
0≤0.61.4
Synonymous OE?1.03
0≤1.21.6
LoF obs/exp: 34 / 126.8Missense obs/exp: 1209 / 1495.8Syn Z: -0.59

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SPTBN2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients