UNC45A

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

Basic information

Region (hg38): 15:90930179-90954093

Links

ENSG00000140553 ∙ NCBI:55898 ∙ OMIM:611219 ∙ HGNC:30594 ∙ Uniprot:Q9H3U1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• osteootohepatoenteric syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteootohepatoenteric syndrome	AR	Audiologic/Otolaryngologic; Gastrointestinal	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; The condition may include intractable secretory diarrhea. which may require parenteral nutrition	Audiologic/Otolaryngologic; Gastrointestinal; Musculoskeletal	29429573

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UNC45A gene.

• Cholestasis-edema syndrome, Norwegian type (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UNC45A 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				148	7	155
missense			256	9	6	271
nonsense			7			7
start loss						0
frameshift			5			5
inframe indel			3			3
splice donor/acceptor (+/-2bp)		2	2	1		5
splice region			12	22	4	38
non coding	1		3	74	5	83
Total	1	2	276	232	18

Highest pathogenic variant AF is 0.0000132

Variants in UNC45A

This is a list of pathogenic ClinVar variants found in the UNC45A region.

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

Position	Type	Phenotype	Significance	ClinVar
15-90931401-C-T			Likely benign (Oct 01, 2023)
15-90931719-G-T		not specified	Uncertain significance (Oct 05, 2023)
15-90931721-T-C		not specified	Uncertain significance (Dec 07, 2023)
15-90931781-C-T		not specified	Uncertain significance (Feb 14, 2023)
15-90931823-T-C		not specified	Uncertain significance (Jun 16, 2024)
15-90935227-G-T		Cholestasis-edema syndrome, Norwegian type	Pathogenic (Feb 01, 2024)
15-90935328-A-G		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
15-90935336-T-TG			Uncertain significance (Jan 31, 2022)
15-90935347-C-T			Uncertain significance (Nov 18, 2021)
15-90935354-G-A			Likely benign (Jan 12, 2023)
15-90935354-G-T			Uncertain significance (May 13, 2022)
15-90935355-C-T			Uncertain significance (Sep 01, 2022)
15-90935356-C-A			Uncertain significance (Jan 11, 2022)
15-90935356-C-T			Uncertain significance (Sep 27, 2022)
15-90935357-C-A		UNC45A-related disorder	Likely benign (Jan 16, 2024)
15-90935359-G-C		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
15-90935360-G-A			Likely benign (Oct 13, 2023)
15-90935368-C-G			Uncertain significance (Jul 03, 2022)
15-90935368-C-T			Uncertain significance (Nov 08, 2021)
15-90935372-C-T			Likely benign (Aug 27, 2022)
15-90935377-T-C		Osteootohepatoenteric syndrome	Likely pathogenic (Oct 18, 2022)
15-90935380-G-A			Likely benign (Jan 20, 2024)
15-90935383-C-A			Likely benign (Sep 22, 2022)
15-90935388-C-T			Likely benign (Jul 23, 2022)
15-90935529-C-T			Likely benign (Oct 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UNC45A	protein_coding	protein_coding	ENST00000418476	20	23914

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.27e-11	0.999	125397	1	350	125748	0.00140

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.192	562	575	0.977	0.0000347	6082
Missense in Polyphen		181	188.73	0.95904		1916
Synonymous	-0.296	248	242	1.02	0.0000148	1952
Loss of Function	3.00	25	47.2	0.529	0.00000259	517

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00182	0.00175
Ashkenazi Jewish	0.00596	0.00597
East Asian	0.000330	0.000326
Finnish	0.000324	0.000323
European (Non-Finnish)	0.00186	0.00185
Middle Eastern	0.000330	0.000326
South Asian	0.000428	0.000425
Other	0.00131	0.00130

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as co-chaperone for HSP90. Prevents the stimulation of HSP90AB1 ATPase activity by AHSA1. Positive factor in promoting PGR function in the cell. May be necessary for proper folding of myosin (Potential). Necessary for normal cell proliferation. Necessary for normal myotube formation and myosin accumulation during muscle cell development. May play a role in erythropoiesis in stroma cells in the spleen (By similarity). {ECO:0000250, ECO:0000269|PubMed:12119110, ECO:0000269|PubMed:16478993, ECO:0000305}.

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.891
• rvis_EVS: -1.1
• rvis_percentile_EVS: 6.95

Haploinsufficiency Scores

• pHI: 0.123
• hipred: Y
• hipred_score: 0.706
• ghis: 0.589

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.913

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Unc45a
• Phenotype: vision/eye phenotype; hematopoietic system 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: unc45a
• Affected structure: primary head sinus
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: muscle organ development;cell differentiation;chaperone-mediated protein folding
• Cellular component: Golgi apparatus;cytosol;nuclear speck;perinuclear region of cytoplasm
• Molecular function: protein binding;cadherin binding;Hsp90 protein binding