NLRX1

protein-coding

NLR family member X1, the group of NLR family

Gene summary

The protein encoded by this gene is a member of the NLR family and localizes to the outer mitochondrial membrane. The encoded protein is a regulator of mitochondrial antivirus responses. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2013]

MANE transcript

NM_001282144.2

Inheritance

—

ClinVar variants

U:186B:14

Top phenotype

Long QT syndrome

gnomAD constraint

pLI —, LoF o/e 1.19

Max pathogenic AF

—

Genomic locus

chr11:119,166,568-119,184,016

External References & Databases

Ensembl (ENSG00000160703)

Transcript & Mutation Effects

hg38 • Region Span ~17.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NLRX1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 177

not providedTotal: 29

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001282144.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	1 clinvar	1 clinvar	7
missense			179 clinvar	10 clinvar	2 clinvar	191
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	186	11	3	200

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001282144.2	RefSeq	NP_001269073.1	9	MANE Select
ENST00000409109.6	Ensembl	ENSP00000387334.1	9	MANE Select
NM_001282143.2	RefSeq	NP_001269072.1	9	Standard
NM_001282358.2	RefSeq	NP_001269287.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Influenza A - Homo sapiens (human)
NOD-like receptor signaling pathway - Homo sapiens (human)
RIG-I-like receptor signaling pathway - Homo sapiens (human)
RIG-I-like Receptor Signaling
DDX58/IFIH1-mediated induction of interferon-alpha/beta

Biological Process

viral process
negative regulation of type I interferon production
negative regulation of interferon-beta production
negative regulation of interleukin-6 production
intracellular signal transduction

Molecular Function

protein binding
ATP binding

Cellular Component

cytoplasm
mitochondrion
mitochondrial outer membrane
plasma membrane
cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409109
Coding exons: 9
Length: 17449
Individuals with no LoFs: 125337
Homozygous LoFs: 1
Heterozygous LoFs: 410
Defined: 125748
p: 0.00164

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.134	604	613	0.985	0.0000427	6192
Missense (PolyPhen)		189	204.79	0.92289		2345
Synonymous	0.429	251	260	0.966	0.0000163	2210
Loss of Function	-1.07	42	35.2	1.19	0.00000219	346

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0030	0.0030	notable
Latino/Admixed American	0.0018	0.0018	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.0013	0.0013	notable
European (Non-Finnish)	0.0012	0.0012	notable
South Asian	0.0043	0.0043	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Participates in antiviral signaling. Acts as a negative regulator of MAVS-mediated antiviral responses, through the inhibition of the virus-induced RLH (RIG-like helicase)-MAVS interaction (PubMed:18200010). Instead, promotes autophagy by interacting with TUFM and subsequently recruiting the autophagy- related proteins ATG5 and ATG12 (PubMed:22749352). Regulates also MAVS-dependent NLRP3 inflammasome activation to attenuate apoptosis (PubMed:27393910). Has no inhibitory function on NF- kappa-B signaling pathway, but enhances NF-kappa-B and JUN N- terminal kinase dependent signaling through the production of reactive oxygen species (PubMed:18219313). {ECO:0000269|PubMed:18200010, ECO:0000269|PubMed:18219313, ECO:0000269|PubMed:22749352, ECO:0000269|PubMed:27393910}.;

Recessive Scores

pRec: 0.134

Intolerance Scores

LoFtool: 0.946
RVIS EVS: 0.19
RVIS percentile EVS: 66.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.564

Gene Damage Prediction

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