MYO18B

myosin XVIIIB, the group of Myosin heavy chains, class XVIII

Basic information

Region (hg38): 22:25742144-26031045

Links

ENSG00000133454

∙ NCBI:84700 ∙ OMIM:607295 ∙ HGNC:18150 ∙ Uniprot:Q8IUG5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome (Definitive), mode of inheritance: AR
Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome (Moderate), mode of inheritance: AR
Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome (Strong), mode of inheritance: AR
Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome (Supportive), mode of inheritance: AR
Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome (Moderate), mode of inheritance: AR
Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Klippel-Feil syndrome 4, autosomal recessive, with nemaline myopathy and facial dysmorphism	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	25748484

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYO18B gene.

not_provided (1968 variants)
Inborn_genetic_diseases (404 variants)
Klippel-Feil_anomaly-myopathy-facial_dysmorphism_syndrome (142 variants)
MYO18B-related_disorder (98 variants)
not_specified (9 variants)
Limb-girdle_muscular_dystrophy (2 variants)
Klippel-Feil_syndrome (2 variants)
HP:0003549 (1 variants)
See_cases (1 variants)
Nemaline_myopathy (1 variants)
Fraser_syndrome_3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYO18B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000032608.7. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	561 clinvar	24 clinvar	592
missense			1015 clinvar	67 clinvar	19 clinvar	1101
nonsense	50 clinvar	11 clinvar	1 clinvar			62
start loss						0
frameshift	31 clinvar	11 clinvar	2 clinvar			44
splice donor/acceptor (+/-2bp)	1 clinvar	21 clinvar	1 clinvar			23
Total	82	43	1026	628	43

Highest pathogenic variant AF is 0.00014130176

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYO18B	protein_coding	protein_coding	ENST00000335473	42	288897

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.03e-31	1.00	124535	0	245	124780	0.000982

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.177	1443	1.46e+3	0.987	0.0000907	16483
Missense in Polyphen		446	457.6	0.97465		5347
Synonymous	-0.201	603	597	1.01	0.0000381	5053
Loss of Function	4.19	70	119	0.586	0.00000609	1358

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00327	0.00323
Ashkenazi Jewish	0.000101	0.0000993
East Asian	0.000904	0.000890
Finnish	0.0000955	0.0000928
European (Non-Finnish)	0.000875	0.000857
Middle Eastern	0.000904	0.000890
South Asian	0.00127	0.00124
Other	0.00151	0.00148

dbNSFP

Source: dbNSFP

Function: FUNCTION: 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.;
Disease: DISEASE: Klippel-Feil syndrome 4, autosomal recessive, with nemaline myopathy and facial dysmorphism (KFS4) [MIM:616549]: A form of Klippel-Feil syndrome, a skeletal disorder characterized by congenital fusion of cervical vertebrae. It is due to a failure in the normal segmentation of vertebrae during the early weeks of fetal development. The clinical triad consists of short neck, low posterior hairline, and limited neck movement. KFS4 features additionally include myopathy, mild short stature, microcephaly, and distinctive facies. {ECO:0000269|PubMed:25748484}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.108

Intolerance Scores

loftool: 0.0545
rvis_EVS: 1.21
rvis_percentile_EVS: 93.02

Haploinsufficiency Scores

pHI: 0.162
hipred: N
hipred_score: 0.358
ghis: 0.479

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.125

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

Gene name: Myo18b
Phenotype: homeostasis/metabolism phenotype; muscle phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Zebrafish Information Network

Gene name: myo18b
Affected structure: fast muscle cell
Phenotype tag: abnormal
Phenotype quality: disorganized

Gene ontology

Biological process: vasculogenesis;in utero embryonic development;cardiac muscle fiber development
Cellular component: nucleus;unconventional myosin complex;Z disc;filamentous actin
Molecular function: motor activity;actin binding;ATP binding