NRROS

Chr 3AR

negative regulator of reactive oxygen species

Also known as: ELLP3030, GARPL1, LRRC33, SENEBAC, UNQ3030

NCBI Gene: 375387 ENSG00000174004 UniProt: Q86YC3 OMIM: 615322

NRROS encodes a key regulator of TGF-beta-1 activation that is specifically required for microglia function in the nervous system, where it associates with latency-associated peptide to enable localized TGF-beta-1 signaling. Biallelic mutations cause autosomal recessive early-onset seizures with neurodegeneration and brain calcification. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.531), consistent with its essential role in microglial regulation of neuroinflammation.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables transforming growth factor beta binding activity. Predicted to be involved in several processes, including microglia development; sequestering of TGFbeta in extracellular matrix; and transforming growth factor beta receptor signaling pathway. Located in cell surface. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Seizures, early-onset, with neurodegeneration and brain calcificationMIM #618875

Clinical highlights

Gene-disease validity (ClinGen)

seizures, early-onset, with neurodegeneration and brain calcifications · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.53

LOEUF

LOF

Mechanism· G2P