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.

• Autosomal_recessive_limb-girdle_muscular_dystrophy_type_2L (1000 variants)
• Gnathodiaphyseal_dysplasia (997 variants)
• not_provided (475 variants)
• Inborn_genetic_diseases (83 variants)
• not_specified (63 variants)
• Miyoshi_muscular_dystrophy_3 (53 variants)
• ANO5-Related_Muscle_Diseases (46 variants)
• Autosomal_recessive_limb-girdle_muscular_dystrophy (33 variants)
• ANO5-related_disorder (33 variants)
• Limb-girdle_muscular_dystrophy,_recessive (25 variants)
• Miyoshi_myopathy (25 variants)
• Elevated_circulating_creatine_kinase_concentration (6 variants)
• Myopathy (5 variants)
• Intellectual_disability (3 variants)
• Abnormality_of_the_musculature (3 variants)
• Limb-girdle_muscular_dystrophy (3 variants)
• Distal_muscle_weakness (2 variants)
• Fatty_replacement_of_skeletal_muscle (2 variants)
• Muscle_tissue_disorder (2 variants)
• Muscular_dystrophy (2 variants)
• ANO5_Muscle_Disease (1 variants)
• Hereditary_fructosuria (1 variants)
• Lower_limb_amyotrophy (1 variants)
• ANO5-related_muscular_dystrophy (1 variants)
• Lower_limb_muscle_weakness (1 variants)
• See_cases (1 variants)
• Polycystic_kidney_disease (1 variants)
• Acute_rhabdomyolysis (1 variants)
• Achilles_tendon_contracture (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. These statistics are base on transcript: NM_000213599.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	17	164	1	183
missense	12	43	548	16	4	623
nonsense	37	19	1			57
start loss				1		1
frameshift	36	15	7	1		59
splice donor/acceptor (+/-2bp)	7	29	2	2		40
Total	92	107	575	184	5

Highest pathogenic variant AF is 0.002081966

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