SPTBN2

Chr 11

spectrin beta, non-erythrocytic 2

NCBI Gene: 6712ENSG00000173898UniProt: O15020

Probably plays an important role in neuronal membrane skeleton

Primary Disease Associations & Inheritance

UniProtSpinocerebellar ataxia 5
UniProtSpinocerebellar ataxia, autosomal recessive, 14
665
ClinVar variants
21
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SPTBN2
🧬
Gene-Disease Validity (ClinGen)
spinocerebellar ataxia type 5 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 421 VUS of 665 total submissions
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?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.27 (0.20–0.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.77–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 34 / 126.8Missense obs/exp: 1209 / 1495.8Syn Z: -0.59

ClinVar Variant Classifications

665 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic8
VUS421
Likely Benign174
Benign18
Conflicting31
13
Pathogenic
8
Likely Pathogenic
421
VUS
174
Likely Benign
18
Benign
31
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
7
0
13
Likely Pathogenic
2
1
5
0
8
VUS
1
387
27
6
421
Likely Benign
0
22
38
114
174
Benign
0
2
0
16
18
Conflicting
—31
Total841377136665

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

View in 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.

Gene2Phenotype Curations

SPTBN2-related infantile ataxia with oculomotor and pyramidal signs

strong
ADDominant NegativeAltered Gene Product Structure
Dev. Disorders
G2P ↗

SPTBN2-related spinocerebellar ataxia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — SPTBN2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Heterozygous variants in SPTBN1 cause intellectual disability and autism.
Rosenfeld JA et al.·Am J Med Genet A
2021
Targeted exome analysis identifies the genetic basis of disease in over 50% of patients with a wide range of ataxia-related phenotypes.
Sun M et al.·Genet Med
2019Cohort
Spectrins: molecular organizers and targets of neurological disorders.
Lorenzo DN et al.·Nat Rev Neurosci
2023Review
Extreme phenotypic heterogeneity in non-expansion spinocerebellar ataxias.
Cunha P et al.·Am J Hum Genet
2023
The natural history of progressive myoclonus ataxia.
van der Veen S et al.·Neurobiol Dis
2024Natural history
A Novel Homozygous Mutation in SPTBN2 Leads to Spinocerebellar Ataxia in a Consanguineous Family: Report of a New Infantile-Onset Case and Brief Review of the Literature.
Al-Muhaizea MA et al.·Cerebellum
2018Review
Heterozygous missense variants of SPTBN2 are a frequent cause of congenital cerebellar ataxia.
Nicita F et al.·Clin Genet
2019
Two novel missense variants in SPTBN2 likely associated with spinocerebellar ataxia type 5.
Bian X et al.·Neurol Sci
2021
Expanding the Landscape of Spinocerebellar Ataxia Type 5.
Benevides ML et al.·Neuropediatrics
2022Review
Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias.
Martínez-Rubio D et al.·Int J Mol Sci
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools