ADD3

Chr 10AR

adducin 3

ENSG00000148700 UniProt: Q9UEY8 OMIM: 601568

ADD3 encodes adducin gamma, a membrane-cytoskeleton-associated protein that promotes assembly of the spectrin-actin network and plays critical roles in actin filament capping, podocyte structure and function, and neurite growth. Mutations cause autosomal recessive cerebral palsy with spastic quadriplegia. The gene is highly constrained against loss-of-function variants (pLI = 0.999, LOEUF = 0.246), indicating intolerance to protein-truncating mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Plays a role in actin filament capping (PubMed:23836506). Binds to calmodulin (Probable). Involved in myogenic reactivity of the renal afferent arteriole (Af-art), renal interlobular arteries and middle cerebral artery (MCA) to increased perfusion pressure. Involved in regulation of potassium channels in the vascular smooth muscle cells (VSMCs) of the Af-art and MCA ex vivo. Involved in regulation of glomerular capillary pressure, glomerular filtration rate (GFR) and glomerular nephrin expression in response to hypertension. Involved in renal blood flow (RBF) autoregulation. Plays a role in podocyte structure and function. Regulates globular monomer actin (G-actin) and filamentous polymer actin (F-actin) ratios in the primary podocytes affecting actin cytoskeleton organization. Regulates expression of synaptopodin, RhoA, Rac1 and CDC42 in the renal cortex and the primary podocytes. Regulates expression of nephrin in the glomeruli and in the primary podocytes, expression of nephrin and podocinin in the renal cortex, and expression of focal adhesion proteins integrin alpha-3 and integrin beta-1 in the glomeruli. Involved in cell migration and cell adhesion of podocytes, and in podocyte foot process effacement. Regulates expression of profibrotics markers MMP2, MMP9, TGF beta-1, tubular tight junction protein E-cadherin, and mesenchymal markers vimentin and alpha-SMA (By similarity). Promotes the growth of neurites (By similarity)

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cerebral palsy, spastic quadriplegic, 3MIM #617008

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder with motor features · ARModerateconsider for supplementary testing

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.25

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)