ANO5

anoctamin 5, the group of Anoctamins

Basic information

Region (hg38): 11:21782659-22283567

Previous symbols: [ "TMEM16E", "LGMD2L" ]

Links

ENSG00000171714 ∙ NCBI:203859 ∙ OMIM:608662 ∙ HGNC:27337 ∙ Uniprot:Q75V66 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive limb-girdle muscular dystrophy type 2L (Limited), mode of inheritance: AR
• gnathodiaphyseal dysplasia (Supportive), mode of inheritance: AD
• autosomal recessive limb-girdle muscular dystrophy type 2L (Supportive), mode of inheritance: AR
• gnathodiaphyseal dysplasia (Moderate), mode of inheritance: AD
• gnathodiaphyseal dysplasia (Strong), mode of inheritance: AD
• autosomal recessive limb-girdle muscular dystrophy type 2L (Strong), mode of inheritance: AR
• Miyoshi muscular dystrophy 3 (Strong), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Gnathodiaphyseal dysplasia	AD	Allergy/Immunology/Infectious	Individuals have been reported as being frequently affected by osteomyelitis of the jaw, and awareness of the risk may allow early detection and management of lesions	Allergy/Immunology/Infectious; Musculoskeletal	5816667; 9673985; 15124103; 17132147; 17008331; 20096397; 20692837; 21186264; 22951575; 21820307; 22402862; 22499103; 23047743

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ANO5 gene.

• not provided (39 variants)
• Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L (36 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia (21 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2L (14 variants)
• Miyoshi muscular dystrophy 3 (5 variants)
• Autosomal recessive limb-girdle muscular dystrophy (3 variants)
• Gnathodiaphyseal dysplasia (2 variants)
• Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L;Miyoshi muscular dystrophy 3 (2 variants)
• Miyoshi muscular dystrophy 3;Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L (1 variants)
• Miyoshi muscular dystrophy 3;Autosomal recessive limb-girdle muscular dystrophy type 2L (1 variants)
• Gnathodiaphyseal dysplasia;Miyoshi muscular dystrophy 3;Autosomal recessive limb-girdle muscular dystrophy type 2L (1 variants)
• Miyoshi muscular dystrophy 3;Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia (1 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia;Miyoshi muscular dystrophy 3 (1 variants)
• Abnormality of the musculature (1 variants)
• ANO5-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANO5 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			13	115	2	130
missense	4	19	472	7	2	504
nonsense	38	12	1			51
start loss			1			1
frameshift	31	7	4			42
inframe indel			7			7
splice donor/acceptor (+/-2bp)	6	24	1			31
splice region	2	1	49	41	1	94
non coding			68	147	59	274
Total	79	62	567	269	63

Highest pathogenic variant AF is 0.000118

Variants in ANO5

This is a list of pathogenic ClinVar variants found in the ANO5 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-22192586-C-G			Uncertain significance (Apr 01, 2022)
11-22193232-A-C		Miyoshi myopathy • Limb-girdle muscular dystrophy, recessive • ANO5-Related Muscle Diseases	Conflicting classifications of pathogenicity (Jul 15, 2018)
11-22193242-T-G		ANO5-Related Muscle Diseases	Uncertain significance (Jan 13, 2018)
11-22193276-G-T		Miyoshi myopathy • Limb-girdle muscular dystrophy, recessive • Autosomal recessive limb-girdle muscular dystrophy type 2L • ANO5-Related Muscle Diseases • Gnathodiaphyseal dysplasia • Miyoshi muscular dystrophy 3	Benign/Likely benign (Dec 05, 2021)
11-22193283-G-C		Limb-girdle muscular dystrophy, recessive • Miyoshi myopathy • ANO5-Related Muscle Diseases	Uncertain significance (Jan 13, 2018)
11-22193292-C-A		ANO5-Related Muscle Diseases	Uncertain significance (Jan 13, 2018)
11-22193299-G-T		Limb-girdle muscular dystrophy, recessive • Miyoshi myopathy • ANO5-Related Muscle Diseases	Uncertain significance (Jan 12, 2018)
11-22193331-A-G		ANO5-Related Muscle Diseases • Limb-girdle muscular dystrophy, recessive • Miyoshi myopathy	Uncertain significance (Jan 13, 2018)
11-22193331-A-AAGGAGGAGGGGAATGAGGAGGAGG		Miyoshi myopathy • Limb-girdle muscular dystrophy, recessive • Gnathodiaphyseal dysplasia	Benign (May 28, 2019)
11-22193357-G-C		Limb-girdle muscular dystrophy, recessive • Miyoshi myopathy • not specified • Autosomal recessive limb-girdle muscular dystrophy type 2L • Miyoshi muscular dystrophy 3 • ANO5-Related Muscle Diseases • Gnathodiaphyseal dysplasia	Benign (Jul 14, 2021)
11-22193428-G-C		Miyoshi myopathy • Limb-girdle muscular dystrophy, recessive • ANO5-Related Muscle Diseases	Uncertain significance (Jan 13, 2018)
11-22193476-T-TTAACGAGCTGGCGAAGA			Uncertain significance (May 25, 2017)
11-22193492-G-A			Uncertain significance (Dec 10, 2020)
11-22193498-C-T		Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L	Uncertain significance (Jun 06, 2021)
11-22193503-C-A		Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia	Uncertain significance (Feb 22, 2022)
11-22193503-C-G		Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L	Uncertain significance (Mar 08, 2022)
11-22193503-C-T		Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L	Uncertain significance (Mar 17, 2023)
11-22193505-G-A		Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L • Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 19, 2023)
11-22193508-C-T		Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia	Uncertain significance (May 05, 2023)
11-22193510-C-T		Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L	Conflicting classifications of pathogenicity (Jul 11, 2022)
11-22193511-C-T		Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L	Conflicting classifications of pathogenicity (Jan 18, 2024)
11-22193514-G-A		Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L	Uncertain significance (Jun 04, 2022)
11-22193514-G-C		Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia	Uncertain significance (Mar 26, 2021)
11-22193514-G-T		Gnathodiaphyseal dysplasia;Autosomal recessive limb-girdle muscular dystrophy type 2L	Pathogenic (Oct 17, 2021)
11-22193523-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2L;Gnathodiaphyseal dysplasia	Uncertain significance (Oct 10, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ANO5	protein_coding	protein_coding	ENST00000324559	22	90182

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.85e-22	0.312	125318	3	426	125747	0.00171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.117	467	474	0.985	0.0000239	6040
Missense in Polyphen		168	181.52	0.92553		2417
Synonymous	-1.80	192	163	1.18	0.00000820	1635
Loss of Function	1.86	42	57.2	0.734	0.00000328	657

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00254	0.00248
Ashkenazi Jewish	0.00	0.00
East Asian	0.000382	0.000381
Finnish	0.000556	0.000554
European (Non-Finnish)	0.00286	0.00282
Middle Eastern	0.000382	0.000381
South Asian	0.000490	0.000490
Other	0.00181	0.00179

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Does not exhibit calcium-activated chloride channel (CaCC) activity. {ECO:0000269|PubMed:20056604, ECO:0000269|PubMed:23047743}.
• Disease: DISEASE: Limb-girdle muscular dystrophy 2L (LGMD2L) [MIM:611307]: An autosomal recessive degenerative myopathy characterized by proximal weakness, weakness of the hip and shoulder girdles and prominent asymmetrical quadriceps femoris and biceps brachii atrophy. {ECO:0000269|PubMed:20096397, ECO:0000269|PubMed:22499103, ECO:0000269|PubMed:25864073, ECO:0000269|PubMed:25891276}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Miyoshi muscular dystrophy 3 (MMD3) [MIM:613319]: A late- onset muscular dystrophy characterized by distal muscle weakness of the lower limbs, calf muscle discomfort and weakness, quadriceps atrophy. Muscle weakness and atrophy may be asymmetric. {ECO:0000269|PubMed:20096397, ECO:0000269|PubMed:22499103}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Stimuli-sensing channels;Ion channel transport;Transport of small molecules (Consensus)

Recessive Scores

• pRec: 0.117

Intolerance Scores

• loftool: 0.971
• rvis_EVS: 0.58
• rvis_percentile_EVS: 82.34

Haploinsufficiency Scores

• pHI: 0.110
• hipred: N
• hipred_score: 0.329
• ghis: 0.486

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.261

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ano5
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; reproductive system phenotype

Gene ontology

• Biological process: chloride transport;ion transmembrane transport
• Cellular component: endoplasmic reticulum membrane;plasma membrane;integral component of membrane;vesicle
• Molecular function: intracellular calcium activated chloride channel activity;protein dimerization activity