MYO18B

Chr 22AR

myosin XVIIIB

NCBI Gene: 84700ENSG00000133454UniProt: Q8IUG5

May be involved in intracellular trafficking of the muscle cell when in the cytoplasm, whereas entering the nucleus, may be involved in the regulation of muscle specific genes. May play a role in the control of tumor development and progression; restored MYO18B expression in lung cancer cells suppresses anchorage-independent growth

Primary Disease Associations & Inheritance

Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphismMIM #616549
AR
2547
ClinVar variants
39
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MYO18B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 218 VUS of 2547 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.71LOEUF
pLI 0.000
Z-score 4.19
OE 0.59 (0.48–0.71)
Tolerant

Typical tolerance to LoF variation

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.
0.18Z-score
OE missense 0.99 (0.94–1.03)
1443 obs / 1462.0 exp
Tolerant

Mild missense constraint

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.0.59 (0.48–0.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.94–1.03)
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.1.01
0≤1.21.6
LoF obs/exp: 70 / 119.4Missense obs/exp: 1443 / 1462.0Syn Z: -0.20

ClinVar Variant Classifications

2547 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic11
VUS218
Likely Benign219
Benign1
Conflicting2
28
Pathogenic
11
Likely Pathogenic
218
VUS
219
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
0
14
0
28
Likely Pathogenic
8
0
3
0
11
VUS
2
210
6
0
218
Likely Benign
0
6
88
125
219
Benign
0
0
0
1
1
Conflicting
—2
Total24216111126479

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

View in ClinVar →

Protein Context — Lollipop Plot

MYO18B · protein map & ClinVar variants

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

Gene2Phenotype Curations

MYO18B-related Klippel-Feil syndrome with nemaline myopathy and facial dysmorphism

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
MYOSIN XVIIIB; MYO18B
MIM #607295 · *

Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism

MIM #616549

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Myosin18B predicts favorable prognosis of cutaneous squamous-cell carcinoma.
Cao C et al.·Genes Genomics
2021
Integrative DNA methylome and transcriptome analysis identify potential genes on the influence of dilated cardiomyopathy-associated heart failure.
Guo Z et al.·Clin Epigenetics
2025
MYO18B promotes hepatocellular carcinoma progression by activating PI3K/AKT/mTOR signaling pathway.
Zhang Z et al.·Diagn Pathol
2018
Genome-Wide Association and Inheritance-Based Analyses Implicate Unconventional Myosin Genes in Hypoplastic Left Heart Syndrome.
Theis JL et al.·Circ Genom Precis Med
2023
A novel pathogenic variant in MYO18B associating early-onset muscular hypotonia, and characteristic dysmorphic features, delineation of the phenotypic spectrum of MYO18B-related conditions.
Brunet T et al.·Gene
2020Case report
Myo18b is essential for sarcomere assembly in fast skeletal muscle.
Berger J et al.·Hum Mol Genet
2017
Further delineation of MYO18B-related autosomal recessive Klippel-Feil syndrome with myopathy and facial dysmorphism.
Altuame FD et al.·Am J Med Genet A
2021
[Clinical Characteristics and Genetic Analysis of Klippel-Feil Syndrome].
Li ZQ et al.·Zhongguo Yi Xue Ke Xue Yuan Xue Bao
2021
The mutational burden and oligogenic inheritance in Klippel-Feil syndrome.
Li Z et al.·BMC Musculoskelet Disord
2020
A population-specific uncommon variant in GRIN3A associated with schizophrenia.
Takata A et al.·Biol Psychiatry
2013Meta-analysis
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