NRROS

negative regulator of reactive oxygen species

Basic information

Region (hg38): 3:196639694-196662004

Previous symbols: [ "LRRC33" ]

Links

ENSG00000174004 ∙ NCBI:375387 ∙ OMIM:615322 ∙ HGNC:24613 ∙ Uniprot:Q86YC3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• seizures, early-onset, with neurodegeneration and brain calcifications (Strong), mode of inheritance: AR
• seizures, early-onset, with neurodegeneration and brain calcifications (Moderate), mode of inheritance: AR
• seizures, early-onset, with neurodegeneration and brain calcifications (Strong), mode of inheritance: AR
• seizures, early-onset, with neurodegeneration and brain calcifications (Strong), mode of inheritance: AR
• seizures, early-onset, with neurodegeneration and brain calcifications (Definitive), mode of inheritance: AR
• seizures, early-onset, with neurodegeneration and brain calcifications (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Seizures, early-onset, with neurodegeneration and brain calcification	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	32100099; 32197075

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NRROS gene.

• Inborn_genetic_diseases (87 variants)
• Seizures,_early-onset,_with_neurodegeneration_and_brain_calcifications (19 variants)
• not_provided (13 variants)
• NRROS-related_disorder (2 variants)
• not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NRROS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000198565.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	1	3
missense	2		84	10	1	97
nonsense	2	3				5
start loss						0
frameshift	3	2				5
splice donor/acceptor (+/-2bp)						0
Total	7	5	84	12	2

Highest pathogenic variant AF is 0.0000041045455

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NRROS	protein_coding	protein_coding	ENST00000328557	2	22319

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.326	0.674	125733	0	14	125747	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.892	379	431	0.879	0.0000290	4473
Missense in Polyphen		77	115.03	0.66937		1475
Synonymous	-0.611	223	212	1.05	0.0000152	1531
Loss of Function	2.96	4	17.2	0.232	8.26e-7	181

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000617	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000797	0.0000791
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000981	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGFB1, and regulates integrin- dependent activation of TGF-beta-1 (By similarity). TGF-beta-1 activation mediated by LRRC33/NRROS is highly localized: there is little spreading of TGF-beta-1 activated from one microglial cell to neighboring microglia, suggesting the existence of localized and selective activation of TGF-beta-1 by LRRC33/NRROS (By similarity). Indirectly plays a role in Toll-like receptor (TLR) signaling: ability to inhibit TLR-mediated NF-kappa-B activation and cytokine production is probably a consequence of its role in TGF-beta-1 signaling (PubMed:23545260). {ECO:0000250|UniProtKB:Q8BMT4, ECO:0000269|PubMed:23545260}.
• Pathway: TYROBP Causal Network (Consensus)

Intolerance Scores

• rvis_EVS: -0.68
• rvis_percentile_EVS: 15.36

Haploinsufficiency Scores

• pHI: 0.417
• hipred: Y
• hipred_score: 0.631
• ghis: 0.548

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: K

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nrros
• Phenotype: cellular phenotype; immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: superoxide metabolic process;inflammatory response;immune response;transforming growth factor beta receptor signaling pathway;microglia development;sequestering of TGFbeta in extracellular matrix;transforming growth factor beta1 activation;innate immune response
• Cellular component: extracellular region;endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;cell surface;integral component of membrane
• Molecular function: transforming growth factor beta binding