NRROS (negative regulator of reactive oxygen species)

Gene

• Entrez ID: 375387
• Gene name: Negative regulator of reactive oxygen species
• Gene symbol: NRROS
• Synonyms (NCBI Gene): ELLP3030, GARPL1, LRRC33, SENEBAC, UNQ3030
• Chromosome: 3
• Chromosome location: 3q29

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005615	Component	Extracellular space	IBA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005783	Component	Endoplasmic reticulum	ISS
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0006801	Process	Superoxide metabolic process	ISS
GO:0006954	Process	Inflammatory response	IEA
GO:0006954	Process	Inflammatory response	ISS
GO:0006955	Process	Immune response	IBA
GO:0006955	Process	Immune response	IEA
GO:0006955	Process	Immune response	ISS
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IBA
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IEA
GO:0009986	Component	Cell surface	IDA	29909984
GO:0009986	Component	Cell surface	IEA
GO:0014005	Process	Microglia development	IEA
GO:0014005	Process	Microglia development	ISS
GO:0016020	Component	Membrane	IEA
GO:0019838	Function	Growth factor binding	IEA
GO:0035583	Process	Sequestering of TGFbeta in extracellular matrix	IEA
GO:0035583	Process	Sequestering of TGFbeta in extracellular matrix	ISS
GO:0045087	Process	Innate immune response	ISS
GO:0050431	Function	Transforming growth factor beta binding	IBA
GO:0050431	Function	Transforming growth factor beta binding	IEA
GO:0050431	Function	Transforming growth factor beta binding	IPI	29909984
GO:0141069	Function	Receptor ligand inhibitor activity	IEA
GO:0141069	Function	Receptor ligand inhibitor activity	ISS

Other IDs

• MIM: 615322
• HGNC: 24613
• e!Ensembl: ENSG00000174004

Protein

• UniProt ID: Q86YC3
• Protein name: Transforming growth factor beta activator LRRC33 (Leucine-rich repeat-containing protein 33) (Negative regulator of reactive oxygen species)
• Protein function: Key regulator of transforming growth factor beta-1 (TGFB1) specifically required for microglia function in the nervous system (By similarity). Required for activation of latent TGF-beta-1 in macrophages and microglia: associates specifically via
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13855	LRR_8	81 → 144	Leucine rich repeat	Repeat
  PF13855	LRR_8	157 → 217	Leucine rich repeat	Repeat
  PF13855	LRR_8	328 → 388	Leucine rich repeat	Repeat
  PF13516	LRR_6	424 → 440	Leucine Rich repeat	Repeat

• Tissue specificity: TISSUE SPECIFICITY: Mainly expressed in cells of hematopoietic origin (PubMed:29909984). Highly expressed in bone marrow, thymus, liver, lung, intestine and spleen (PubMed:23545260). In the brain, highly expressed in microglia (PubMed:32100099). {ECO:0000
• Sequence:

  MELLPLWLCLGFHFLTVGWRNRSGTATAASQGVCKLVGGAADCRGQSLASVPSSLPPHAR
  MLTLDANPLKTLWNHSLQPYPLLESLSLHSCHLERISRGAFQEQGHLRSLVLGDNCLSEN
  YEETAAALHALPGLRRLDLSGNALTEDMAALMLQNLSSLRSVSLAGNTIMRLDDSVFEGL
  ERLRELDLQRNYIFEIEGGAFDGLAELRHLNLAFNNLPCIVDFGLTRLRVLNVSYNVLEW
  FLATGGEAAFELETLDLSHNQLLFFPLLPQYSKLRTLLLRDNNMGFYRDLYNTSSPREMV
  AQFLLVDGNVTNITTVSLWEEFSSSDLADLRFLDMSQNQFQYLPDGFLRKMPSLSHLNLH
  QNCLMTLHIREHEPPGALTELDLSHNQLSELHLAPGLASCLGSLRLFNLSSNQLLGVPPG
  LFANARNITTLDMSHNQISLCPLPAASDRVGPPSCVDFRNMASLRSLSLEGCGLGALPDC
  PFQGTSLTYLDLSSNWGVLNGSLAPLQDVAPMLQVLSLRNMGLHSSFMALDFSGFGNLRD
  LDLSGNCLTTFPRFGGSLALETLDLRRNSLTALPQKAVSEQLSRGLRTIYLSQNPYDCCG
  VDGWGALQHGQTVADWAMVTCNLSSKIIRVTELPGGVPRDCKWERLDLGLLYLVLILPSC
  LTLLVACTVIVLTFKKPLLQVIKSRCHWSSVY

• Sequence length: 692

Pathways

KEGG:

TGF-beta signaling pathway

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
NRROS-related disorder	Likely pathogenic	rs1239560651	RCV003402991	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Seizures, early-onset, with neurodegeneration and brain calcifications	Pathogenic; Likely pathogenic	rs2108643149, rs1324029062, rs2474180806, rs1201594317, rs1737677036, rs1737495759, rs868389022, rs1737685202, rs1737672350, rs762737130	RCV002221673 RCV002221674 RCV003140616 RCV003443468 RCV001093641 RCV001093642 RCV001093643 RCV001093644 RCV001093645 RCV001093646	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATOPIC ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MULTIPLE SCLEROSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Baraitser Brett Piesowicz syndrome	Associate	32197075	★☆☆☆☆ Found in Text Mining only
Calcinosis	Associate	35099671	★☆☆☆☆ Found in Text Mining only
Drug Resistant Epilepsy	Associate	32197075	★☆☆☆☆ Found in Text Mining only
Fahr's disease	Associate	35099671	★☆☆☆☆ Found in Text Mining only
Inflammation	Associate	32197075	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Associate	31600200	★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Associate	35099671	★☆☆☆☆ Found in Text Mining only
Neoplasms	Associate	31600200	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Associate	32197075, 35099671	★☆☆☆☆ Found in Text Mining only
Paroxysmal ventricular fibrillation	Associate	37239478	★☆☆☆☆ Found in Text Mining only
Seizures	Associate	32197075	★☆☆☆☆ Found in Text Mining only
Vitiligo	Associate	37239478	★☆☆☆☆ Found in Text Mining only