SPTBN4

Chr 19

spectrin beta, non-erythrocytic 4

Also known as: CMND, NEDHND, QV, SPNB4, SPTBN3

NCBI Gene: 57731ENSG00000160460UniProt: Q9H254

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 localizes to the nuclear matrix, PML nuclear bodies, and cytoplasmic vesicles. A highly similar gene in the mouse is required for localization of specific membrane proteins in polarized regions of neurons. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with hypotonia, neuropathy, and deafness

Clinical highlights

Gene-disease validity (ClinGen)
neurodevelopmental disorder with hypotonia, neuropathy, and deafness · ARDefinitivesufficient evidence for diagnostic panels
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
10
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.19
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — SPTBN4
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.19LOEUF
pLI 1.000
Z-score 8.48
OE 0.12 (0.08–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
3.93Z-score
OE missense 0.70 (0.66–0.74)
958 obs / 1367.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.12 (0.08–0.19)
0≤0.351.4
Missense OE?0.70 (0.66–0.74)
0≤0.61.4
Synonymous OE?0.85
0≤1.21.6
LoF obs/exp: 13 / 108.1Missense obs/exp: 958 / 1367.4Syn Z: 2.79

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SPTBN4 · 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.

Search ClinicalTrials.gov →

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