SPEG

Chr 2

striated muscle enriched protein kinase

Also known as: APEG-1, APEG1, BPEG, CNM5, MYLK6, SPEGalpha, SPEGbeta

NCBI Gene: 10290ENSG00000072195UniProt: Q15772

This gene encodes a protein with similarity to members of the myosin light chain kinase family. This protein family is required for myocyte cytoskeletal development. Along with the desmin gene, expression of this gene may be controlled by the desmin locus control region. Mutations in this gene are associated with centronuclear myopathy 5. [provided by RefSeq, Jun 2016]

Primary Disease Associations & Inheritance

UniProtMyopathy, centronuclear, 5
564
ClinVar variants
30
Pathogenic / LP
0.92
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SPEG
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Gene-Disease Validity (ClinGen)
myopathy, centronuclear, 5 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 324 VUS of 564 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
LoF intolerant — likely haploinsufficient
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.
0.29LOEUF
pLI 0.923
Z-score 8.24
OE 0.21 (0.15–0.29)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
2.78Z-score
OE missense 0.82 (0.79–0.85)
1541 obs / 1879.7 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.0.21 (0.15–0.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.79–0.85)
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.0.96
0≤1.21.6
LoF obs/exp: 27 / 127.2Missense obs/exp: 1541 / 1879.7Syn Z: 1.01

ClinVar Variant Classifications

564 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic6
VUS324
Likely Benign167
Benign25
Conflicting18
24
Pathogenic
6
Likely Pathogenic
324
VUS
167
Likely Benign
25
Benign
18
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
19
0
24
Likely Pathogenic
3
0
3
0
6
VUS
1
307
11
5
324
Likely Benign
0
11
34
122
167
Benign
0
7
6
12
25
Conflicting
—18
Total932573139564

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

View in ClinVar →

Protein Context — Lollipop Plot

SPEG · protein map & ClinVar variants

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

Gene2Phenotype Curations

SPEG-related centronuclear myopathy with dilated cardiomyopathy

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.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A metabolomics pipeline highlights microbial metabolism in bloodstream infections.
Mayers JR et al.·Cell
2024
Striated Preferentially Expressed Protein Kinase (SPEG) in Muscle Development, Function, and Disease.
Luo S et al.·Int J Mol Sci
2021Review
Clinical and genetic analysis of a case with centronuclear myopathy caused by SPEG gene mutation: a case report and literature review.
Zhang G et al.·BMC Pediatr
2021Review
Characterization of a novel zebrafish model of SPEG-related centronuclear myopathy.
Espinosa KG et al.·Dis Model Mech
2022Functional
Identification of novel therapeutic targets for cognitive performance and associations with brain health.
Zhang LY et al.·Transl Psychiatry
2025
Novel SPEG mutations in congenital myopathies: Genotype-phenotype correlations.
Qualls AE et al.·Muscle Nerve
2019Case report
SPEG interacts with myotubularin, and its deficiency causes centronuclear myopathy with dilated cardiomyopathy.
Agrawal PB et al.·Am J Hum Genet
2014
Novel SPEG variant cause centronuclear myopathy in China.
Tang J et al.·J Clin Lab Anal
2020Case report
Mutational and clinical spectrum of centronuclear myopathy in 9 cases and a literature review of Chinese patients.
Wang Q et al.·Neurol Sci
2022Review
Dilated-Left Ventricular Non-Compaction Cardiomyopathy in a Pediatric Case with SPEG Compound Heterozygous Variants.
Jaouadi H et al.·Int J Mol Sci
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Relationship between the expression of striated preferentially expressed gene (SPEG) and the development of atrial fibrillation.
Wei J et al.·J Thorac Dis
2025🔓 Open Access
Effects of Peanut Rust Disease (Puccinia arachidis Speg.) on Agricultural Production: Current Control Strategies and Progress in Breeding for Resistance.
You Y et al.·Genes (Basel)
2024🔓 Open Access
Speg interactions that regulate the stability of excitation-contraction coupling protein complexes in triads and dyads.
Lee CS et al.·Commun Biol
2023🔓 Open Access
Novel SPEG variants in a neonate with severe dilated cardiomyopathy and relatively mild hypotonia.
Fujimoto HM et al.·Hum Genome Var
2023🔓 Open Access
Didymella fabae Punith.: mating type occurrence, distribution and phenotyping of the anamorph Ascochyta fabae Speg. in Tunisia.
Omri Ben Youssef N et al.·Front Plant Sci
2023🔓 Open Access
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