SPTBN1

Chr 2AD

spectrin beta, non-erythrocytic 1

Also known as: DDISBA, ELF, HEL102, SPTB2, betaSpII

NCBI Gene: 6711ENSG00000115306UniProt: Q01082

Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is composed of two antiparallel dimers of alpha- and beta- subunits. This gene is one member of a family of beta-spectrin genes. The encoded protein contains an N-terminal actin-binding domain, and 17 spectrin repeats which are involved in dimer formation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Developmental delay, impaired speech, and behavioral abnormalitiesMIM #619475
AD
0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SPTBN1
🧬
Gene-Disease Validity (ClinGen)
developmental delay, impaired speech, and behavioral abnormalities · ADStrong

Strong evidence — appropriate for clinical testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.09LOEUF
pLI 1.000
Z-score 9.70
OE 0.04 (0.02–0.09)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
4.54Z-score
OE missense 0.66 (0.62–0.70)
931 obs / 1411.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.04 (0.02–0.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.66 (0.62–0.70)
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.1.18
0≤1.21.6
LoF obs/exp: 5 / 119.4Missense obs/exp: 931 / 1411.2Syn Z: -3.44

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SPTBN1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SPTBN1-related developmental disorder

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental delay, impaired speech, and behavioral abnormalities

MIM #619475

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome.
Cousin MA et al.·Nat Genet
2021
Heterozygous variants in SPTBN1 cause intellectual disability and autism.
Rosenfeld JA et al.·Am J Med Genet A
2021
SPTBN1 and cancer, which links?
Chen S et al.·J Cell Physiol
2020Review
Aldehydes alter TGF-β signaling and induce obesity and cancer.
Yang X et al.·Cell Rep
2024
Spectrins: molecular organizers and targets of neurological disorders.
Lorenzo DN et al.·Nat Rev Neurosci
2023Review
βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases.
Yang P et al.·Int J Biol Sci
2021Review
Genome Sequencing of Idiopathic Speech Delay.
Eising E et al.·Hum Mutat
2024
Recent advances in novel mutation genes of Parkinson's disease.
Yang J et al.·J Neurol
2023Review
Identification of sixteen novel candidate genes for late onset Parkinson's disease.
Gialluisi A et al.·Mol Neurodegener
2021
SPTBN1 abrogates renal clear cell carcinoma progression via glycolysis reprogramming in a GPT2-dependent manner.
Wu J et al.·J Transl Med
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Mechanistic study of miR‑369‑3p in regulating the Wnt/β‑catenin signaling pathway via targeting SPTBN1 in inflammatory response and bone destruction of rheumatoid arthritis.
Wu A et al.·Mol Med Rep
2026🔓 Open Access
SPTBN1 overexpression ameliorates atherosclerosis by inhibiting oxidative stress and inflammation via regulating the TRIM37/TRAF2/NF-κB pathway.
Wu S et al.·Eur J Med Res
2025🔓 Open Access
A Case of Infantile Epileptic Spasms Syndrome with the SPTBN1 Mutation and Review of βII-Spectrin Variants.
Jang HN et al.·Genes (Basel)
2025🔓 Open AccessReview
IGF2BP3 recruits NUDT21 to regulate SPTBN1 alternative polyadenylation and drive ovarian cancer progression.
Luo X et al.·Commun Biol
2025🔓 Open Access
Osteocyte Sptbn1 Deficiency Alters Cell Survival and Mechanotransduction Following Formation of Plasma Membrane Disruptions (PMD) from Mechanical Loading.
Hagan ML et al.·Calcif Tissue Int
2024
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