ANO5

Summary

ANO5 (anoctamin 5, HGNC:27337) is a protein-coding gene on chromosome 11p14.3, encoding Anoctamin-5 (Q75V66). Plays a role in plasma membrane repair in a process involving annexins.

This gene encodes a member of the anoctamin family of transmembrane proteins. The encoded protein is likely a calcium activated chloride channel. Mutations in this gene have been associated with gnathodiaphyseal dysplasia. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 203859 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive limb-girdle muscular dystrophy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 14
• Clinical variants (ClinVar): 1,568 total — 113 pathogenic, 60 likely-pathogenic
• Phenotypes (HPO): 72
• MANE Select transcript: NM_213599

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27337
Approved symbol	ANO5
Name	anoctamin 5
Location	11p14.3
Locus type	gene with protein product
Status	Approved
Aliases	GDD1
Ensembl gene	ENSG00000171714
Ensembl biotype	protein_coding
OMIM	608662
Entrez	203859

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 12 protein_coding, 6 protein_coding_CDS_not_defined, 6 retained_intron, 1 nonsense_mediated_decay

ENST00000324559, ENST00000532043, ENST00000648804, ENST00000664026, ENST00000682084, ENST00000682089, ENST00000682266, ENST00000682341, ENST00000682428, ENST00000682530, ENST00000682684, ENST00000683197, ENST00000683411, ENST00000683437, ENST00000683613, ENST00000683812, ENST00000683834, ENST00000683897, ENST00000684365, ENST00000684663, ENST00000878904, ENST00000878905, ENST00000939029, ENST00000950081, ENST00000950082

RefSeq mRNA: 4 — MANE Select: NM_213599 NM_001142649, NM_001410963, NM_001410964, NM_213599

CCDS: CCDS31444, CCDS91450, CCDS91451

Canonical transcript exons

ENST00000324559 — 22 exons

Exon	Start	End
ENSE00001138482	22262946	22263043
ENSE00001138489	22262129	22262298
ENSE00001205955	22270312	22270442
ENSE00001285789	22211264	22211314
ENSE00001285838	22257680	22257754
ENSE00001285852	22250951	22251011
ENSE00001285862	22236163	22236276
ENSE00001285891	22221097	22221210
ENSE00001285904	22218246	22218287
ENSE00001285929	22203804	22203850
ENSE00001291671	22193085	22193532
ENSE00001317368	22250741	22250846
ENSE00001324619	22250237	22250371
ENSE00001330238	22259519	22259741
ENSE00001349575	22279544	22283357
ENSE00001349621	22239569	22239684
ENSE00001349627	22227302	22227586
ENSE00001349629	22225984	22226052
ENSE00001401082	22255371	22255522
ENSE00003526319	22274569	22274747
ENSE00003618227	22276094	22276199
ENSE00003653161	22272784	22272989

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 98.33.

FANTOM5 (CAGE): breadth broad, TPM avg 6.1827 / max 340.1562, expressed in 613 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113450	4.9721	566
113452	0.3097	87
113456	0.2104	86
113449	0.1920	110
113455	0.1216	55
113451	0.1191	61
206226	0.0843	47
113448	0.0831	35
113453	0.0574	16
113454	0.0330	14

Top tissues by expression

252 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	98.33	gold quality
left ventricle myocardium	UBERON:0006566	98.31	gold quality
vastus lateralis	UBERON:0001379	98.07	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.04	gold quality
quadriceps femoris	UBERON:0001377	97.97	gold quality
deltoid	UBERON:0001476	97.72	gold quality
biceps brachii	UBERON:0001507	97.36	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.03	gold quality
skeletal muscle tissue	UBERON:0001134	96.49	gold quality
myocardium	UBERON:0002349	96.23	gold quality
tibialis anterior	UBERON:0001385	95.54	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.42	gold quality
muscle tissue	UBERON:0002385	94.37	gold quality
middle temporal gyrus	UBERON:0002771	94.03	gold quality
dorsal root ganglion	UBERON:0000044	93.98	gold quality
tibia	UBERON:0000979	93.74	gold quality
heart right ventricle	UBERON:0002080	93.72	gold quality
body of tongue	UBERON:0011876	92.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.57	gold quality
gastrocnemius	UBERON:0001388	91.06	gold quality
muscle of leg	UBERON:0001383	90.01	gold quality
trigeminal ganglion	UBERON:0001675	89.99	gold quality
tongue	UBERON:0001723	88.31	gold quality
cardiac ventricle	UBERON:0002082	86.00	gold quality
heart left ventricle	UBERON:0002084	85.78	gold quality
cardiac atrium	UBERON:0002081	85.24	gold quality
endothelial cell	CL:0000115	84.94	gold quality
right atrium auricular region	UBERON:0006631	84.37	gold quality
primary visual cortex	UBERON:0002436	84.23	gold quality
heart	UBERON:0000948	84.00	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	686.38
E-GEOD-81608	yes	16.48
E-CURD-112	yes	16.31
E-GEOD-83139	yes	9.25
E-ANND-3	yes	6.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

207 targeting ANO5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4789-5P	99.98	70.76	2721

Literature-anchored findings (GeneRIF, showing 40)

• Recessive mutations were identified in ANO5 that result in a proximal limb-girdle muscular dystrophy (LGMD2L) in three French Canadian families and in a distal non-dysferlin Miyoshi myopathy (MMD3) in Dutch and Finnish families. (PMID:20096397)
• mutation in patients with a distal myopathy;(a new separate clinical, genetic and histopathologic entity) (PMID:20692837)
• A founder mutation in Anoctamin 5 is a major cause of limb-girdle muscular dystrophy. (PMID:21186264)
• The c.191dupA mutation, already reported as a founder mutation in Caucasian patients with anoctamin myopathies, was found in our family in a heterozygous state. (PMID:22336395)
• Mutations are distributed all over the gene, indicating that muscular dystrophy caused by ANO5 can be expected to occur in all populations (PMID:22402862)
• This study identified four novel mutations in the ANO5 gene cause high lever Creatine Kinase and limb girdle muscular weakness and Miyoshi type of muscular dystrophy. (PMID:22499103)
• occurrence and molecular epidemiology of LGMD2L, caused by mutations in the anoctamin 5 (ANO5) gene, in a Italian cohort differed from those observed in other European countries. (PMID:22742934)
• This study demonistrayed that anoctamin 5 mutations associate to distal muscular dystrophy. (PMID:22980764)
• Dilated cardiomyopathy is associated with mutations in the ANO5 gene. (PMID:23041008)
• By sequencing the entire ANO5 gene coding region and untranslated regions in a large Italian gnathodiaphyseal dyplasia family, a novel missense mutation causing the p.Thr513Ile substitution, was found. (PMID:23047743)
• A family is described in which 2 mutations in ANO5 segregate with marked creatine kinase-type hypercreatinemia, demonstrating that recessively inherited ANO5 mutations not only lead to muscular dystrophy but may also cause bone disease. (PMID:23055322)
• investigated the prevalence and spectrum of ANO5 gene mutations and related clinical phenotypes; study confirmed that ANO5 gene mutations are responsible for about one fourth of cases of undiagnosed muscular dystrophy in the population studied (PMID:23606453)
• a diagnosis of ANO5 causing Muscular Dystrophy, Limb-Girdle, Type 2L, in 16% of the families (11/68) in a well-defined limb girdle muscular dystrophy cohort in the Netherlands (PMID:23607914)
• ANO5 mutations can be associated with amyloid deposition in muscle (PMID:23663589)
• A high prevalence of ANO5 deficiency was found among patients with unclassified recessive limb girdle muscular dystrophy 2 (PMID:23670307)
• This study showed that TMEM16E possesses distinct function other than chloride channel activity, and another protein-stabilizing machinery toward the TMEM16E proteins should be considered for the on-set regulation of their phenotypes in tissues. (PMID:23843187)
• The present report describes an association between LGMD2L consequent upon mutation in ANO5 and macular dystrophy in one affected person. (PMID:24232312)
• supervised aerobic exercise training is safe and effective in improving oxidative capacity and muscle function in patients with anoctamin 5 deficiency (PMID:24639367)
• Study screened the ANO5 gene in 786 myopathic patients and 52 controls by combining NGS and Sanger sequencing. In the cohort of patients, thirty-three are homozygous or compound heterozygous for causative mutations in ANO5 (PMID:25891276)
• Here we show that Ano5-deficient mice have reduced capacity to repair the sarcolemma following laser-induced damage, exhibit delayed regeneration after cardiotoxin injury and suffer from defective myoblast fusion necessary for the proper repair and regeneration of multinucleated myotubes. these data suggest that ANO5 plays an important role in sarcolemmal membrane dynamics. (PMID:26911675)
• A heterozygous mutation in the ANO5 gene c.1067G > A (p.Cys356Tyr) was identified in both affected individuals in a Russian family with giant cementoma and bone fractures consistent with a diagnosis of gnathodiaphyseal dysplasia. (PMID:27216912)
• Study characterized 12 newly identified and 2 previously identified patients with ANO5 mutations from 11 families. Material was genetically homogeneous with most patients homozygous for the Finnish founder variant c.2272C>T (p.Arg758Cys). In one family, study found a novel p.Met470Arg variant compound heterozygous with p.Arg758Cys. (PMID:27911336)
• After Ano5 gene knock-down with shRNA in MC3T3-E1 osteoblast precursors the authors saw elevated expression of osteoblast-related genes such as Col1a1, osteocalcin, osterix and Runx2 as well as increased mineral nodule formation in differentiating cells. The data suggest that ANO5 plays a role in osteoblast differentiation. (PMID:28176803)
• Asymptomatic, sometimes mild hyperCKemia or exercise intolerance is a presentation of ANO5-related myopathy. (PMID:28187523)
• Results show that ANO5 is downregulated in thyroid cancer and, negatively associated with lymph node metastasis. Its inhibition promotes the migration and invasion of thyroid cancer cells suggesting it as a tumor marker. (PMID:28902351)
• First direct demonstration of Ca(2+)-dependent Phospholipid scrambling activity for TMEM16E; this suggests a gain-of-function phenotype related to a Gnathodiaphyseal dysplasia mutation. (PMID:29124309)
• The Limb-girdle muscular dystrophy 2L family was characterized by mild chronic myopathy and bilateral gastrocnemius hypertrophy with obviously increased creatine kinase levels. Pathological changes included atrophy of fibers with interstitial connective tissues hyperplasia. The pathogenic allele was a c.220C> T mutation in the ANO5 gene. (PMID:30235762)
• ANO5-mediated phospholipid scrambling or ionic currents play an important role in muscle repair. (PMID:30257928)
• Through whole-genome sequencing, the novel mutation c.1067G>T (p.C356F) in ANO5 is responsible for the atypical gnathodiaphyseal dysplasia observed in our patients. GDD should be included in the differential diagnosis for patients with fibro-osseous lesions. (PMID:30554457)
• elucidating TMEM16E function (PMID:30672373)
• A novel missense mutation p.C356W in anoctamin 5 (ANO5) gene was successfully identified as the pathogenic mutation by whole-exome sequencing (WES). (PMID:30996299)
• ANO5 mutations in the Polish limb girdle muscular dystrophy patients: Effects on the protein structure. (PMID:31395899)
• Genetic association analysis identifies a role for ANO5 in prostate cancer progression. (PMID:32027096)
• TMEM16E/ANO5 mutations related to bone dysplasia or muscular dystrophy cause opposite effects on lipid scrambling. (PMID:32112655)
• Persistent asymptomatic or mild symptomatic hyperCKemia due to mutations in ANO5: the mildest end of the anoctaminopathies spectrum. (PMID:32367299)
• Anoctamin 5 (ANO5) muscular dystrophy-three different phenotypes and a new histological pattern. (PMID:32399949)
• ANO5-associated Gnathodiaphyseal dysplasia with calvarial doughnut lesions: First report in an Asian Indian with an expanded phenotype. (PMID:32902009)
• Phenotypic Spectrum of Myopathies with Recessive Anoctamin-5 Mutations. (PMID:32925086)
• ANO5 ensures trafficking of annexins in wounded myofibers. (PMID:33496727)
• Novel ANO5 intronic Roma variant alters splicing causing muscular dystrophy. (PMID:33818761)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ano5a	ENSDARG00000015731
danio_rerio	ano5b	ENSDARG00000036147
mus_musculus	Ano5	ENSMUSG00000055489
rattus_norvegicus	Ano5	ENSRNOG00000015972

Paralogs (10): ANO2 (ENSG00000047617), ANO8 (ENSG00000074855), PPP1R7 (ENSG00000115685), ANO1 (ENSG00000131620), ANO3 (ENSG00000134343), ANO7 (ENSG00000146205), ANO4 (ENSG00000151572), ANO10 (ENSG00000160746), ANO6 (ENSG00000177119), ANO9 (ENSG00000185101)

Protein

Protein identifiers

Anoctamin-5 — Q75V66 (reviewed: Q75V66)

Alternative names: Gnathodiaphyseal dysplasia 1 protein, Transmembrane protein 16E

All UniProt accessions (6): Q75V66, A0A804HHX6, A0A804HJT6, A0A804HKP2, A0A804HL91, A0A804HLK6

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in plasma membrane repair in a process involving annexins. Does not exhibit calcium-activated chloride channel (CaCC) activity.

Subcellular location. Endoplasmic reticulum membrane. Cell membrane.

Tissue specificity. Highly expressed in brain, heart, kidney, lung, and skeletal muscle. Weakly expressed in bone marrow, fetal liver, placenta, spleen, thymus, osteoblasts and periodontal ligament cells.

Disease relevance. Gnathodiaphyseal dysplasia (GDD) [MIM:166260] Rare skeletal syndrome characterized by bone fragility, sclerosis of tubular bones, and cemento-osseous lesions of the jawbone. Patients experience frequent bone fractures caused by trivial accidents in childhood; however the fractures heal normally without bone deformity. The jaw lesions replace the tooth-bearing segments of the maxilla and mandible with fibrous connective tissues, including various amounts of cementum-like calcified mass, sometimes causing facial deformities. Patients also have a propensity for jaw infection and often suffer from purulent osteomyelitis-like symptoms, such as swelling of and pus discharge from the gums, mobility of the teeth, insufficient healing after tooth extraction and exposure of the lesions into the oral cavity. The disease is caused by variants affecting the gene represented in this entry. Muscular dystrophy, limb-girdle, autosomal recessive 12 (LGMDR12) [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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. The term ‘anoctamin’ was coined because these channels are anion selective and have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology.

Similarity. Belongs to the anoctamin family.

RefSeq proteins (4): NP_001136121, NP_001397892, NP_001397893, NP_998764* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007632	Anoctamin	Family
IPR032394	Anoct_dimer	Domain
IPR049452	Anoctamin_TM	Domain

Pfam: PF04547, PF16178

UniProt features (63 total): sequence variant 39, topological domain 9, transmembrane region 8, glycosylation site 6, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q75V66-F1	82.22	0.39

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (6): 335, 366, 380, 768, 778, 791

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-2672351	Stimuli-sensing channels
R-HSA-9733458	Induction of Cell-Cell Fusion
R-HSA-9769739	Regulation of clotting cascade
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-5663205	Infectious disease
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9772573	Late SARS-CoV-2 Infection Events
R-HSA-9824446	Viral Infection Pathways
R-HSA-983712	Ion channel transport

MSigDB gene sets: 266 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_WOUND_HEALING, GOBP_CHLORIDE_TRANSPORT, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, SABATES_COLORECTAL_ADENOMA_DN, GOBP_PHOSPHOLIPID_TRANSPORT, GOBP_MEMBRANE_ORGANIZATION, GOBP_LIPID_LOCALIZATION, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT

GO Biological Process (3): plasma membrane repair (GO:0001778), monoatomic ion transmembrane transport (GO:0034220), chloride transmembrane transport (GO:1902476)

GO Molecular Function (3): intracellularly calcium-gated chloride channel activity (GO:0005229), chloride channel activity (GO:0005254), protein dimerization activity (GO:0046983)

GO Cellular Component (5): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), vesicle (GO:0031982), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Ion channel transport	1
Late SARS-CoV-2 Infection Events	1
Coagulation pathway	1
Disease	1
Viral Infection Pathways	1
SARS-CoV Infections	1
SARS-CoV-2 Infection	1
Infectious disease	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
plasma membrane organization	1
wound healing	1
monoatomic ion transport	1
transmembrane transport	1
chloride transport	1
monoatomic anion transmembrane transport	1
chloride channel activity	1
ligand-gated monoatomic anion channel activity	1
intracellularly calcium-gated channel activity	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
protein binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
membrane-bounded organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

764 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANO5	DYSF	O75923	939
ANO5	NELL1	Q92832	870
ANO5	MMD2	Q8IY49	853
ANO5	FKRP	Q9H9S5	852
ANO5	NELL2	Q99435	845
ANO5	SGCA	Q16586	829
ANO5	SGCB	Q16585	825
ANO5	SGCG	Q13326	810
ANO5	POMT1	Q9Y6A1	774
ANO5	SGCD	Q92629	764
ANO5	FKTN	O75072	754
ANO5	POMT2	Q9UKY4	744
ANO5	TRIM32	Q13049	738
ANO5	TCAP	O15273	724
ANO5	POMGNT1	Q8WZA1	721

IntAct

11 interactions, top by confidence:

A	B	Type	Score
EGFR	CTNND1	psi-mi:“MI:0914”(association)	0.750
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
PTGIR	GPAA1	psi-mi:“MI:0914”(association)	0.350
	ABCD4	psi-mi:“MI:0914”(association)	0.350
ZDHHC12	NBAS	psi-mi:“MI:0914”(association)	0.350
MARCHF4	C2CD2L	psi-mi:“MI:0914”(association)	0.350
MS4A15	ABCD4	psi-mi:“MI:0914”(association)	0.350
OR10H2	ABCD4	psi-mi:“MI:0914”(association)	0.350
TMC4	MARCHF6	psi-mi:“MI:0914”(association)	0.350
EGFR	GGCT	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): ANO5 (Affinity Capture-MS), ANO5 (Affinity Capture-MS), ANO5 (Synthetic Lethality), ANO5 (Proximity Label-MS), ANO5 (Affinity Capture-MS), ANO5 (Proximity Label-MS), ANO5 (Proximity Label-MS), ANO5 (Affinity Capture-RNA), ANO5 (Affinity Capture-MS), ANO5 (Affinity Capture-MS), ANO5 (Affinity Capture-MS), ANO5 (Affinity Capture-MS), ANO5 (Affinity Capture-MS), ANO5 (Affinity Capture-MS), ANO5 (Affinity Capture-MS)

ESM2 similar proteins: A0JN54, A7T1N0, A8DYE2, B3M383, B4GEU5, B4LX81, F4IDQ6, F4INY4, O18784, O35119, O42579, O62852, O88673, P19334, P20192, P22717, P23743, P27730, P34586, P48994, P48995, P49619, P49620, P79100, P91550, Q03603, Q18297, Q2TV84, Q2WEA5, Q4KMQ2, Q5XI69, Q5XXA6, Q61056, Q6DNF3, Q6NS52, Q6P9J9, Q75UR0, Q75V66, Q7Z4N2, Q8BHY3

Diamond homologs: A1A5B4, A2AHL1, A6QLE6, P86044, Q14AT5, Q32M45, Q4KMQ2, Q5XXA6, Q6IFT6, Q6IWH7, Q6P9J9, Q75UR0, Q75V66, Q8BHY3, Q8C5H1, Q8CFW1, Q9BYT9, Q9NQ90, Q6PB70, Q9HCE9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1568 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	113
Likely pathogenic	60
Uncertain significance	779
Likely benign	381
Benign	72

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1008638	NC_000011.9:g.(?22242633)(22242766_?)del	Pathogenic
1029543	NM_213599.3(ANO5):c.2116C>T (p.Arg706Ter)	Pathogenic
1066105	NC_000011.9:g.(?22276907)(22301321_?)del	Pathogenic
1073054	NM_213599.3(ANO5):c.1690C>T (p.Gln564Ter)	Pathogenic
1075891	NM_213599.3(ANO5):c.1924C>T (p.Arg642Ter)	Pathogenic
1076523	NM_213599.3(ANO5):c.823C>T (p.Gln275Ter)	Pathogenic
1323166	NM_213599.3(ANO5):c.1716C>A (p.Cys572Ter)	Pathogenic
1323172	NM_213599.3(ANO5):c.2470C>T (p.Gln824Ter)	Pathogenic
1323192	NM_213599.3(ANO5):c.1593_1597del (p.Phe531fs)	Pathogenic
1323234	NM_213599.3(ANO5):c.1086T>A (p.Tyr362Ter)	Pathogenic
1323242	NM_213599.3(ANO5):c.2433T>A (p.Tyr811Ter)	Pathogenic
1323266	NM_213599.3(ANO5):c.1178G>A (p.Trp393Ter)	Pathogenic
1350152	NC_000011.9:g.(?22242623)(22277088_?)del	Pathogenic
1358563	NM_213599.3(ANO5):c.1656T>G (p.Tyr552Ter)	Pathogenic
1374139	NM_213599.3(ANO5):c.773_774delinsAA (p.Trp258Ter)	Pathogenic
1380487	NM_213599.3(ANO5):c.766C>T (p.Gln256Ter)	Pathogenic
1382777	NM_213599.3(ANO5):c.1944_1945del (p.Lys650fs)	Pathogenic
1396797	NM_213599.3(ANO5):c.22G>T (p.Glu8Ter)	Pathogenic
140553	NM_213599.3(ANO5):c.1733T>C (p.Phe578Ser)	Pathogenic
140555	NM_213599.3(ANO5):c.2018A>G (p.Tyr673Cys)	Pathogenic
1406379	NM_213599.3(ANO5):c.1222del (p.Leu408fs)	Pathogenic
1432460	NC_000011.9:g.(?22225330)(22225416_?)del	Pathogenic
1440062	NM_213599.3(ANO5):c.2193_2197del (p.Gln731fs)	Pathogenic
1453293	NM_213599.3(ANO5):c.1045C>T (p.Gln349Ter)	Pathogenic
1454753	NC_000011.9:g.(?22261105)(22301321_?)del	Pathogenic
1455578	NM_213599.3(ANO5):c.989T>A (p.Leu330Ter)	Pathogenic
1457293	NC_000011.9:g.(?22281045)(22281307_?)del	Pathogenic
1457294	NC_000011.9:g.(?22215039)(22247618_?)del	Pathogenic
1457296	NC_000011.9:g.(?22242623)(22301311_?)del	Pathogenic
1457438	NM_213599.3(ANO5):c.258C>A (p.Tyr86Ter)	Pathogenic

SpliceAI

3519 predictions. Top by Δscore:

Variant	Effect	Δscore
11:22193348:G:GT	donor_gain	1.0000
11:22193514:G:GT	donor_gain	1.0000
11:22211252:T:A	acceptor_gain	1.0000
11:22221085:T:G	acceptor_gain	1.0000
11:22221095:A:AG	acceptor_gain	1.0000
11:22221096:G:GA	acceptor_gain	1.0000
11:22221096:GTTTC:G	acceptor_gain	1.0000
11:22221206:AGGCG:A	donor_gain	1.0000
11:22221207:GGCG:G	donor_gain	1.0000
11:22221207:GGCGG:G	donor_gain	1.0000
11:22221208:GCG:G	donor_gain	1.0000
11:22221208:GCGG:G	donor_gain	1.0000
11:22221209:CGGTA:C	donor_loss	1.0000
11:22221211:G:GG	donor_gain	1.0000
11:22221211:GTAAG:G	donor_loss	1.0000
11:22221212:TAAG:T	donor_loss	1.0000
11:22221213:AAGT:A	donor_loss	1.0000
11:22226109:ACTCT:A	acceptor_gain	1.0000
11:22227402:A:T	donor_gain	1.0000
11:22227582:GAATT:G	donor_gain	1.0000
11:22239543:T:G	acceptor_gain	1.0000
11:22239685:G:GG	donor_gain	1.0000
11:22248748:T:TA	donor_gain	1.0000
11:22248749:A:AA	donor_gain	1.0000
11:22250739:A:AG	acceptor_gain	1.0000
11:22250740:G:GA	acceptor_gain	1.0000
11:22250740:GC:G	acceptor_gain	1.0000
11:22250740:GCA:G	acceptor_gain	1.0000
11:22250740:GCACT:G	acceptor_gain	1.0000
11:22255485:C:G	donor_gain	1.0000

AlphaMissense

6067 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:22226012:T:C	L108P	1.000
11:22236176:T:C	L221P	1.000
11:22270376:T:A	W655R	1.000
11:22270376:T:C	W655R	1.000
11:22221167:T:A	L84H	0.999
11:22221167:T:C	L84P	0.999
11:22225992:A:C	R101S	0.999
11:22225992:A:T	R101S	0.999
11:22226012:T:A	L108H	0.999
11:22226027:T:A	L113H	0.999
11:22226027:T:C	L113P	0.999
11:22227334:G:C	K132N	0.999
11:22227334:G:T	K132N	0.999
11:22227368:G:C	A144P	0.999
11:22227369:C:A	A144D	0.999
11:22236176:T:A	L221H	0.999
11:22236221:G:A	G236E	0.999
11:22236233:T:C	L240P	0.999
11:22236250:T:G	Y246D	0.999
11:22250784:T:A	C353S	0.999
11:22250784:T:C	C353R	0.999
11:22250785:G:C	C353S	0.999
11:22250786:C:G	C353W	0.999
11:22272942:T:A	W730R	0.999
11:22272942:T:C	W730R	0.999
11:22274743:T:A	C804S	0.999
11:22274744:G:C	C804S	0.999
11:22274745:C:G	C804W	0.999
11:22221134:T:C	F73S	0.998
11:22221164:T:A	V83E	0.998

dbSNP variants (sampled 300 via entrez): RS1000037749 (11:22230995 A>G,T), RS1000049477 (11:22224794 C>A,G), RS1000068463 (11:22271942 C>G,T), RS1000082668 (11:22221072 A>G), RS1000083086 (11:22240321 G>A), RS1000131586 (11:22267682 G>T), RS1000132462 (11:22207105 C>G), RS1000157798 (11:22276283 T>C), RS1000168833 (11:22192050 G>A), RS1000173040 (11:22193020 G>A), RS1000199016 (11:22249832 T>C), RS1000243653 (11:22280574 C>A,G), RS1000244746 (11:22200713 A>C), RS1000260142 (11:22242898 T>C,G), RS1000286913 (11:22238730 AT>A,ATT)

Disease associations

OMIM: gene MIM:608662 | disease phenotypes: MIM:166260, MIM:611307, MIM:613319, MIM:253600, MIM:173900, MIM:229600

GenCC curated gene-disease

Disease	Classification	Inheritance
gnathodiaphyseal dysplasia	Definitive	Autosomal dominant
autosomal recessive limb-girdle muscular dystrophy type 2L	Strong	Autosomal recessive
Miyoshi muscular dystrophy 3	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy	Definitive	AR
gnathodiaphyseal dysplasia	Definitive	AD

Mondo (11): gnathodiaphyseal dysplasia (MONDO:0008151), autosomal recessive limb-girdle muscular dystrophy type 2L (MONDO:0012652), Miyoshi muscular dystrophy 3 (MONDO:0013222), autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152), limb-girdle muscular dystrophy (MONDO:0016971), intellectual disability (MONDO:0001071), myopathy (MONDO:0005336), polycystic kidney disease (MONDO:0020642), hereditary fructose intolerance (MONDO:0009249), muscular dystrophy (MONDO:0020121), muscle tissue disorder (MONDO:0003939)

Orphanet (8): Anoctamin-5-related limb-girdle muscular dystrophy R12 (Orphanet:206549), Gnathodiaphyseal dysplasia (Orphanet:53697), Distal anoctaminopathy (Orphanet:399096), Autosomal recessive limb-girdle muscular dystrophy (Orphanet:102015), Limb-girdle muscular dystrophy (Orphanet:263), Hereditary fructose intolerance (Orphanet:469), Muscular dystrophy (Orphanet:98473), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

72 total (30 of 72 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000935	Thickened cortex of long bones
HP:0000938	Osteopenia
HP:0001239	Wrist flexion contracture
HP:0001288	Gait disturbance
HP:0001371	Flexion contracture
HP:0001430	Abnormal calf musculature morphology
HP:0001638	Cardiomyopathy
HP:0002515	Waddling gait
HP:0002650	Scoliosis
HP:0002659	Increased susceptibility to fractures
HP:0002754	Osteomyelitis
HP:0002757	Recurrent fractures
HP:0002816	Genu recurvatum
HP:0002913	Myoglobinuria
HP:0002987	Elbow flexion contracture
HP:0003089	Hamstring contractures
HP:0003198	Myopathy
HP:0003201	Rhabdomyolysis
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003323	Progressive muscle weakness
HP:0003326	Myalgia
HP:0003445	EMG: neuropathic changes
HP:0003458	EMG: myopathic abnormalities
HP:0003482	EMG: axonal abnormality
HP:0003547	Shoulder girdle muscle weakness
HP:0003551	Difficulty climbing stairs
HP:0003552	Muscle stiffness
HP:0003555	Muscle fiber splitting

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001877_46	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	6.000000e-06
GCST002417_3	Plasma thyroid-stimulating hormone levels	2.000000e-08
GCST006014_34	Creatine kinase levels	1.000000e-21
GCST008309_6	Cardiac troponin-I levels	6.000000e-10
GCST009391_1028	Metabolite levels	6.000000e-06
GCST009391_210	Metabolite levels	2.000000e-06
GCST009391_2102	Metabolite levels	6.000000e-07
GCST009549_1	Pruritus in nonalcoholic steatohepatitis	2.000000e-06
GCST011826_3	Computer vision syndrome	9.000000e-06
GCST90011898_81	Alanine aminotransferase levels	5.000000e-10
GCST90011899_30	Aspartate aminotransferase levels	8.000000e-26
GCST90013405_57	Liver enzyme levels (alanine transaminase)	6.000000e-14
GCST90013663_26	Alanine aminotransferase levels	3.000000e-12
GCST90013664_77	Aspartate aminotransferase levels	9.000000e-31

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004534	creatine kinase measurement
EFO:0010071	cardiac troponin I measurement
EFO:0010540	thiamine measurement
EFO:0010373	phosphatidylcholine 32:1 measurement
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009135	Muscular Diseases	C05.651; C10.668.491
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
D049288	Muscular Dystrophies, Limb-Girdle	C05.651.534.500.280; C10.668.491.175.500.149; C16.320.577.280
D007690	Polycystic Kidney Diseases	C12.050.351.968.419.403.875; C12.200.777.419.403.875; C12.950.419.403.875; C16.131.077.717; C16.320.184.625
C538640	Limb-girdle muscular dystrophy autosomal recessive (supp.)
C567645	Miyoshi Muscular Dystrophy 3 (supp.)
C566968	Muscular Dystrophy, Limb-Girdle, Type 2L (supp.)
C536039	Osteogenesis imperfecta, Levin type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	7
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Phthalic Acids	increases methylation	1
Rotenone	decreases expression	1
Silicon Dioxide	increases expression	1
Aflatoxin B1	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SC61	HAP1 ANO5 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

298 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00120055	PHASE4	COMPLETED	Association Between Systemic Exposure of Atorvastatin and Metabolites and Atorvastatin-induced Myotoxicity
NCT03633565	PHASE4	UNKNOWN	Comparative Study of Strategies for Management of Duchenne Myopathy (DM)
NCT03783923	PHASE3	TERMINATED	A Study of Deflazacort (Emflaza®) in Participants With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)
NCT06246513	PHASE3	ACTIVE_NOT_RECRUITING	A Trial to Learn More About an Experimental Gene Therapy Called Bidridistrogene Xeboparvovec (SRP-9003) as a Possible Treatment for Limb Girdle Muscular Dystrophy 2E/R4
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT01225614	PHASE3	UNKNOWN	Efficacy and Tolerance of Early Launching of Nocturnal Non Invasive
NCT04054375	PHASE2	COMPLETED	Weekly Steroids in Muscular Dystrophy
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02140814	PHASE2	COMPLETED	Uncontrolled, Open Label, Pilot and Feasibility Study of Niacinamide in Polycystic Kidney Disease
NCT02558595	PHASE2	COMPLETED	Pilot Study of Niacinamide in Polycystic Kidney Disease (NIAC-PKD2)
NCT02697617	PHASE2	COMPLETED	Use of Low Dose Pioglitazone to Treat Autosomal Dominant Polycystic Kidney Disease
NCT00873782	PHASE1	COMPLETED	Safety Study of Transvenous Limb Perfusion in Human Muscular Dystrophy
NCT01344798	PHASE1	COMPLETED	Clinical Study of AAV1-gamma-sarcoglycan Gene Therapy for Limb Girdle Muscular Dystrophy Type 2C
NCT02050776	PHASE1	WITHDRAWN	Stem Cell Therapy in Limb Girdle Muscular Dystrophy
NCT02245711	PHASE1	WITHDRAWN	Cell Therapy in Limb Girdle Muscular Dystrophy
NCT05876780	PHASE1	ACTIVE_NOT_RECRUITING	A Gene Transfer Single Dose Study to Evaluate the Safety, Tolerability and Efficacy of SRP-9003 in Non-Ambulatory and Ambulatory Participants With Limb Girdle Muscular Dystrophy, Type 2E/R4 (Beta-Sarcoglycan [β-SG] Deficiency)
NCT05906251	PHASE1	TERMINATED	A Gene Transfer Study to Evaluate the Safety, Tolerability and Efficacy of SRP-6004 in Ambulatory Participants With Limb Girdle Muscular Dystrophy, Type 2B/R2 (LGMD2B/R2, Dysferlin [DYSF] Related)
NCT06747273	PHASE1	TERMINATED	Study to Evaluate the Safety, Tolerability, and Efficacy of SRP-9004 Administered by Systemic Infusion in Limb Girdle Muscular Dystrophy Type 2D/R3 Participants in the United States
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00278564	PHASE1	TERMINATED	Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases
NCT02166489	PHASE1	COMPLETED	Mesenchymal Stem Cells Transplantation in Patients With Chronic Renal Failure Due to Polycystic Kidney Disease
NCT06155214	Not specified	UNKNOWN	Developmental Regression-related Disease Research and Achievement Transformation Innovation Team
NCT05989620	Not specified	RECRUITING	Long-Term Development of Muscular Dystrophy Outcome Assessments
NCT01126697	PHASE2/PHASE3	COMPLETED	Clinical Trial of Coenzyme Q10 and Lisinopril in Muscular Dystrophies
NCT00104078	PHASE1/PHASE2	COMPLETED	Study Evaluating MYO-029 in Adult Muscular Dystrophy
NCT02579239	PHASE1/PHASE2	COMPLETED	Evaluate Safety and Biological Activity of ATYR1940 in Participants With Limb Girdle Muscular Dystrophy 2B (LGMD2B) and Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT02836418	PHASE1/PHASE2	COMPLETED	Study to Evaluate the Long-Term Safety, Tolerability, and Biological Activity of ATYR1940 in Participants With Limb Girdle and Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT05230459	PHASE1/PHASE2	RECRUITING	A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)
NCT05588401	PHASE1/PHASE2	UNKNOWN	Evaluating Safety and Efficacy of Autologous Gene-edited Muscle Stem Cells (GenPHSats-bASKet)