MYO18B

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

Basic information

Region (hg38): 22:25742143-26031045

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

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 (63 variants)
• Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome (8 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	486	28	517
missense			869	37	31	937
nonsense	43	7	2			52
start loss						0
frameshift	24	11	1			36
inframe indel			6			6
splice donor/acceptor (+/-2bp)	1	15	1			17
splice region			40	47	9	96
non coding			4	186	152	342
Total	68	33	886	709	211

Highest pathogenic variant AF is 0.000171

Variants in MYO18B

This is a list of pathogenic ClinVar variants found in the MYO18B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-25746524-CA-TC			Uncertain significance (Dec 11, 2023)
22-25746525-A-C			Benign (Feb 01, 2024)
22-25761101-C-G		Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome	Benign (Feb 01, 2024)
22-25761108-C-T			Uncertain significance (Apr 09, 2021)
22-25761109-G-A			Uncertain significance (Nov 05, 2021)
22-25761109-G-T			Uncertain significance (Mar 12, 2022)
22-25761112-T-G		Inborn genetic diseases	Uncertain significance (Aug 04, 2023)
22-25761113-C-T		MYO18B-related disorder	Likely benign (Jan 04, 2024)
22-25761114-G-A		Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome	Uncertain significance (Dec 21, 2023)
22-25761116-C-T			Likely benign (Aug 02, 2022)
22-25761123-G-T			Pathogenic (Nov 21, 2023)
22-25761145-A-T			Likely benign (Dec 03, 2023)
22-25761177-A-G			Benign (May 13, 2021)
22-25761332-T-C			Benign (May 13, 2021)
22-25761341-CG-C			Benign (Nov 12, 2018)
22-25761342-G-C			Benign (May 13, 2021)
22-25761347-C-A			Benign (May 13, 2021)
22-25761350-G-C			Benign (May 13, 2021)
22-25761379-AGGT-A			Benign (Jun 21, 2021)
22-25762943-C-G			Benign (Jun 19, 2021)
22-25763216-G-A			Likely benign (Jun 23, 2022)
22-25763216-G-C			Likely benign (Feb 13, 2023)
22-25763223-C-T			Likely benign (Mar 15, 2021)
22-25763234-C-T			Uncertain significance (Sep 12, 2022)
22-25763235-G-A			Uncertain significance (Nov 13, 2023)

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