UNC45B

unc-45 myosin chaperone B, the group of Armadillo like helical domain containing

Basic information

Region (hg38): 17:35147817-35189345

Previous symbols: [ "CMYA4" ]

Links

ENSG00000141161 ∙ NCBI:146862 ∙ OMIM:611220 ∙ HGNC:14304 ∙ Uniprot:Q8IWX7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• early-onset nuclear cataract (Supportive), mode of inheritance: AD
• early-onset posterior subcapsular cataract (Supportive), mode of inheritance: AD
• myofibrillar myopathy 11 (Moderate), mode of inheritance: AR
• cataract 43 (Strong), mode of inheritance: AD
• cataract 43 (Limited), mode of inheritance: Unknown
• myofibrillar myopathy 11 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myofibrillar myopathy 11	AD	Cardiovascular	Among other findings, the condition can involve arrhthymias and cardiomyopathy, and awareness may allow surveillance and early management of these sequelae	Cardiovascular; Musculoskeletal; Ophthalmologic	24549050; 31852522; 33217308

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UNC45B gene.

• UNC45B-related disorder (1 variants)
• Myofibrillar myopathy 11 (1 variants)
• Myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UNC45B 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			1	24	10	35
missense	1		88	12	5	106
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	3	4	8
non coding			1	41	48	90
Total	1	0	90	77	63

Highest pathogenic variant AF is 0.000112

Variants in UNC45B

This is a list of pathogenic ClinVar variants found in the UNC45B region.

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

Position	Type	Phenotype	Significance	ClinVar
17-35148017-G-C			Likely benign (Feb 24, 2020)
17-35148131-G-A			Likely benign (Feb 24, 2020)
17-35148293-G-A			Benign (Jul 17, 2023)
17-35148307-G-A		Inborn genetic diseases	Likely benign (Mar 29, 2023)
17-35148334-C-T		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
17-35148336-G-A		Myofibrillar myopathy 11	Uncertain significance (Nov 22, 2022)
17-35148348-T-G		Inborn genetic diseases	Uncertain significance (Apr 22, 2022)
17-35148359-C-A		UNC45B-related disorder	Likely benign (Dec 22, 2023)
17-35148360-C-T			Benign (Aug 17, 2023)
17-35148376-A-G			Uncertain significance (Jun 01, 2022)
17-35148382-C-A		Inborn genetic diseases	Uncertain significance (Mar 07, 2023)
17-35148407-C-T			Benign (Jan 26, 2024)
17-35148408-C-T		Inborn genetic diseases	Uncertain significance (Sep 27, 2022)
17-35148409-G-A		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)
17-35148412-C-A			Uncertain significance (Aug 04, 2023)
17-35148430-C-T		Inborn genetic diseases	Likely benign (Jul 27, 2022)
17-35148592-G-A			Likely benign (Nov 06, 2019)
17-35148625-C-T			Likely benign (Nov 22, 2019)
17-35148981-C-T			Likely benign (Dec 22, 2022)
17-35148982-G-A			Benign (Jan 27, 2024)
17-35149891-A-G			Likely benign (Feb 24, 2020)
17-35150052-C-A		UNC45B-related disorder	Likely benign (Oct 06, 2022)
17-35150054-A-G		Inborn genetic diseases	Uncertain significance (Dec 12, 2023)
17-35150068-G-A		UNC45B-related disorder	Likely benign (Feb 17, 2022)
17-35150090-G-A		Inborn genetic diseases	Uncertain significance (Jun 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UNC45B	protein_coding	protein_coding	ENST00000268876	19	41529

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.91e-15	0.853	125667	0	81	125748	0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.404	569	543	1.05	0.0000320	6048
Missense in Polyphen		156	154.62	1.0089		1654
Synonymous	0.607	213	225	0.948	0.0000133	1887
Loss of Function	2.04	30	44.8	0.670	0.00000257	496

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000458	0.000458
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000547	0.0000544
Finnish	0.000463	0.000462
European (Non-Finnish)	0.000346	0.000343
Middle Eastern	0.0000547	0.0000544
South Asian	0.000532	0.000523
Other	0.000660	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a co-chaperone for HSP90 and is required for proper folding of the myosin motor domain. Plays a role in sarcomere formation during muscle cell development. Is necessary for normal early lens development. {ECO:0000250|UniProtKB:Q6DGE9, ECO:0000250|UniProtKB:Q8CGY6}.
• Disease: DISEASE: Cataract 43 (CTRCT43) [MIM:616279]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. {ECO:0000269|PubMed:24549050}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.109

Intolerance Scores

• loftool: 0.840
• rvis_EVS: 0.3
• rvis_percentile_EVS: 71.68

Haploinsufficiency Scores

• pHI: 0.218
• hipred: Y
• hipred_score: 0.672
• ghis: 0.517

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Unc45b
• Phenotype: 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: unc45b
• Affected structure: lens fiber cell
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: lens development in camera-type eye;muscle organ development;cell differentiation;chaperone-mediated protein folding
• Cellular component: cytosol
• Molecular function: protein binding;Hsp90 protein binding