ANO5

anoctamin 5

2 disorders 1 untyped 1 causative 11p14.3 gene with protein product

HGNC:27337 Monarch NCBI Gene 203859 ENSG00000171714 UniProt Q75V66 OMIM 608662

Previous symbols: TMEM16E, LGMD2L. Aliases: GDD1.

Normal function · from ai-gene-review (Q75V66, commit 79fe13b38970) · AI-generated, not KB evidence

ANO5 (TMEM16E) is a multipass membrane protein of the anoctamin family with calcium-dependent phospholipid scramblase activity. It resides mainly in the endoplasmic reticulum and reaches the plasma membrane in particular expression and injury contexts. Human ANO5 supports transbilayer lipid redistribution and associated nonselective ion conductance in cell assays. In muscle, ANO5 supports membrane repair and coordinated annexin trafficking after injury; a scrambling-defective chimera can rescue repair, indicating separable functions. Endothelial ANO5 contributes to surface phosphatidylserine exposure. Recessive ANO5 variants cause limb-girdle muscular dystrophy R12 or Miyoshi muscular dystrophy 3, whereas specific dominant variants cause gnathodiaphyseal dysplasia.

Catalyzes transbilayer phospholipid scrambling in calcium-stimulated cell assays. Human constructs support surface lipid exposure, and endothelial ANO5 contributes to phosphatidylserine externalization. The plasma-membrane location describes where this surface lipid-exposure activity was measured; it does not exclude the substantial ER pool. Muscle membrane repair is also an established, biologically central ANO5 role. It is not assigned as a direct consequence of this molecular activity because a scrambling-defective chimera rescues repair. A separate repair activity cannot yet be named from the available experiments: annexin organization and calcium handling are implicated, but ANO5 has not been shown to execute a specific binding, scaffolding, transport or fusion step that explains repair.

molecular function: phospholipid scramblase activity · directly involved in: phospholipid translocation · locations: plasma membrane

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Gnathodiaphyseal Dysplasia	causative germline gain of function	mechanism: Heterozygous ANO5 Missense Variant
Autosomal Recessive Limb-Girdle Muscular Dystrophy	untyped	mechanism: Sarcolemmal Instability and Failed Membrane Repair subtype: LGMDR12 scoped to subtype: LGMDR12

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
gnathodiaphyseal dysplasia MONDO:0008151	AD	Definitive 2025-02-03	Gnathodiaphyseal Dysplasia causative
autosomal recessive limb-girdle muscular dystrophy MONDO:0015152	AR	Definitive 2024-11-14	Autosomal Recessive Limb-Girdle Muscular Dystrophy untyped

Mechanism modules · computed from kb/

sarcolemmal_fragility_myofiber_necrosis via Autosomal Recessive Limb-Girdle Muscular Dystrophy

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.