UNC45A

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

Basic information

Region (hg38): 15:90930180-90954093

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
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.

not_provided (581 variants)
Inborn_genetic_diseases (148 variants)
UNC45A-related_disorder (22 variants)
Osteootohepatoenteric_syndrome (19 variants)
UNC45A-associated_Cholestasis (2 variants)
Diarrhea (2 variants)
Increased_susceptibility_to_fractures (2 variants)
Hearing_impairment (2 variants)
See_cases (2 variants)
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. These statistics are base on transcript: NM_000018671.5. 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			1 clinvar	173 clinvar	10 clinvar	184
missense	4 clinvar	1 clinvar	314 clinvar	13 clinvar	4 clinvar	336
nonsense	2 clinvar		9 clinvar			11
start loss						0
frameshift	1 clinvar	3 clinvar	5 clinvar			9
splice donor/acceptor (+/-2bp)		3 clinvar	2 clinvar	1 clinvar		6
Total	7	7	331	187	14

Highest pathogenic variant AF is 0.000028498642

Loading clinvar variants...

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