NLRX1

Summary

NLRX1 (NLR family member X1, HGNC:29890) is a protein-coding gene on chromosome 11q23.3, encoding NLR family member X1 (Q86UT6). Participates in antiviral signaling.

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.

Source: NCBI Gene 79671 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 222 total
• MANE Select transcript: NM_001282144

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29890
Approved symbol	NLRX1
Name	NLR family member X1
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	NOD9, CLR11.3
Ensembl gene	ENSG00000160703
Ensembl biotype	protein_coding
OMIM	611947
Entrez	79671

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 20 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000292199, ENST00000409109, ENST00000409991, ENST00000422249, ENST00000449394, ENST00000454811, ENST00000468765, ENST00000469103, ENST00000474751, ENST00000481860, ENST00000482180, ENST00000524562, ENST00000525863, ENST00000706727, ENST00000706728, ENST00000706729, ENST00000886077, ENST00000886078, ENST00000886079, ENST00000886080, ENST00000920615, ENST00000964948, ENST00000964949, ENST00000964950, ENST00000964951

RefSeq mRNA: 5 — MANE Select: NM_001282144 NM_001282143, NM_001282144, NM_001282358, NM_024618, NM_170722

CCDS: CCDS44752, CCDS8416

Canonical transcript exons

ENST00000409109 — 10 exons

Exon	Start	End
ENSE00001247225	119172356	119172425
ENSE00001581761	119168725	119169302
ENSE00001588858	119183118	119184016
ENSE00003474511	119174453	119175274
ENSE00003517924	119172901	119172989
ENSE00003554322	119173479	119174098
ENSE00003556717	119171356	119171473
ENSE00003595303	119179693	119180288
ENSE00003633240	119181171	119181257
ENSE00003651979	119182094	119182345

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 94.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1.9434 / max 36.6043, expressed in 1247 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117101	1.7611	1237
117099	0.1484	39
117100	0.0340	15

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	94.56	gold quality
cervix squamous epithelium	UBERON:0006922	92.64	silver quality
esophagus mucosa	UBERON:0002469	91.94	gold quality
epithelium of esophagus	UBERON:0001976	91.82	gold quality
esophagus squamous epithelium	UBERON:0006920	91.78	gold quality
tongue squamous epithelium	UBERON:0006919	91.61	silver quality
squamous epithelium	UBERON:0006914	91.43	gold quality
penis	UBERON:0000989	91.16	gold quality
cervix epithelium	UBERON:0004801	89.90	silver quality
mammalian vulva	UBERON:0000997	89.66	gold quality
pharyngeal mucosa	UBERON:0000355	89.47	gold quality
apex of heart	UBERON:0002098	89.21	gold quality
gingival epithelium	UBERON:0001949	88.66	gold quality
gingiva	UBERON:0001828	88.65	gold quality
oral cavity	UBERON:0000167	88.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.43	gold quality
esophagus	UBERON:0001043	88.30	gold quality
upper arm skin	UBERON:0004263	87.72	gold quality
triceps brachii	UBERON:0001509	87.26	silver quality
vastus lateralis	UBERON:0001379	86.72	silver quality
right uterine tube	UBERON:0001302	86.60	gold quality
quadriceps femoris	UBERON:0001377	86.50	silver quality
gluteal muscle	UBERON:0002000	86.38	silver quality
gastrocnemius	UBERON:0001388	86.00	gold quality
muscle organ	UBERON:0001630	85.96	gold quality
skeletal muscle organ	UBERON:0014892	85.95	gold quality
muscle of leg	UBERON:0001383	85.93	gold quality
heart left ventricle	UBERON:0002084	85.90	gold quality
cardiac ventricle	UBERON:0002082	85.85	gold quality
heart right ventricle	UBERON:0002080	85.76	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.67

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• identification of NLRX1 as a check against mitochondrial antiviral responses–an intersection of three ancient cellular processes: NLR signalling, intracellular virus detection and the use of mitochondria as a platform for anti-pathogen signalling (PMID:18200010)
• These results identify NLRX1 as a NLR that contributes to the link between reactive oxygen species generation at the mitochondria and innate immune responses. (PMID:18219313)
• sequesters MAVS away from RIG-I and thereby prevents mitochondrial anti-viral immunity (PMID:18397740)
• function of NOD-like receptors in the antiviral response [REVIEW] (PMID:18466630)
• NLRX1 has a functional leader sequence and fully translocates to the mitochondrial matrix. (PMID:19692591)
• the presence of NLRX1 is required for optimal chlamydial growth and reactive oxygen species production (PMID:20959452)
• NLRX1 interacts directly with RNA and suggestts a role for NLRX1 in recognition of intracellular viral RNA in antiviral immunity. (PMID:22386589)
• Results showed that missense mutations in transmembrane protein 2 p.Ser1254Asn, interferon alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and complement component 2 p.Glu318Asp were associated with chronic hepatitis B. (PMID:22610944)
• Post-transcriptional inhibition of luciferase reporter assays by the Nod-like receptor proteins NLRX1 and NLRC3. (PMID:22718770)
• NLRX1 attenuated IFN-I production & promoted autophagy during viral infection cells. NLRX1 interacts with TUFM. (PMID:22749352)
• NLRX1 and TUFM work in concert to reduce cytokine response and augment autophagy. (PMID:23321557)
• Together, these results suggest a novel mechanism for rhinovirus-induced epithelial barrier disruption involving NLRX-1 and mitochondrial reactive oxygen species generation. (PMID:24429360)
• NLRX1 acts as a potential tumor suppressor by regulating the TNF-alpha induced cell death and metabolism. (PMID:25639646)
• These data support a model in which CS-dependent NLRX1 inhibition facilitates MAVS/RHL activation and subsequent inflammation, remodeling, protease, cell death, and inflammasome responses. (PMID:25938787)
• NLRX1, NLRP12 and NLRC3 negatively modulate the host immune response following virus exposure. (Review) (PMID:26763980)
• we identify a novel signaling hub centering on the NLRX1 TUFM protein complex, promoting autophagic flux. Defects in the expression of either NLRX1 or TUFM result in compromised autophagy when treated with EGFR inhibitors.These findings expand our understanding of the components involved in head and neck squamous cell carcinoma autophagy machinery that responds to EGFR inhibitors. (PMID:26876213)
• Data show that NLRX1 suppresses tumorigenesis and reveals new genetic pathways involved in the pathobiology of histiocytic sarcoma. (PMID:27105514)
• findings suggest that NLRX1 may function as a cardiac-protective molecule in myocardial ischemic injury by repressing inflammation and apoptosis (PMID:27393910)
• The data suggests that NLRX1 plays a positive role in Kaposi’s sarcoma-associated herpesvirus (KSHV) lytic replication by suppressing the IFNbeta response during the process of KSHV reactivation, which might serve as a potential target for restricting KSHV replication and transmission. (PMID:28459883)
• Study shows that NLRX1 is a proviral host factor for HCV infection and functions as a negative regulator of the HCV-triggered innate immune response. NLRX1 is induced by HCV infection and interacts with MAVS, leading to K48 polyubiquitination and subsequent degradation of MAVS. Its nucleotide binding oligomerization domain is essential for NLRX1 to interact with PCBP2 and subsequently induce MAVS degradation. (PMID:28956771)
• NLRX1 exerted opposing regulatory effects on viral activation of the transcription factors IRF1 and IRF3. NLRX1 suppressed MAVS-mediated activation of IRF3, it conversely facilitated virus-induced increases in IRF1 expression and thereby enhanced control of viral infection. (PMID:28967880)
• downregulated in brain injury following aneurysm (PMID:28993512)
• NOD-like receptor X1 (NLRX1) positively regulates ATP-induced NLR Family, Pyrin Domain-Containing 3 Protein (NLRP3) inflammasome activation through mitochondrial reactive oxygen species in gingival epithelial cells (GECs). NLRX1 acts as a negative regulator of NF-kappaB signaling and IL-8 expression. NLRX1 stimulates detection of the pathogen Fusobacterium nucleatum via the inflammasome, while dampening cytokine produc… (PMID:29024797)
• genetic association studies in Han population in southern China: Data suggest that, in subjects with type 2 diabetes, an SNP in NLRX1 (rs4245191) is associated with macro-vascular complications and cerebral infarction in the population studied; no such association was found for two other SNPs in NLRX1 (rs10790286, rs561830) or for two SNPs in TRAF6 (rs5030445, rs16928973). (TRAF6 = TNF receptor associated factor-6) (PMID:29046236)
• NLRX1 was downregulated in tumor tissue compared with adjacent normal liver tissue. Low tumor NLRX1 expression was identified as an independent indicator for HCC prognosis (recurrence: hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26-2.76, overall survival [OS] 2.26, 95% CI 1.44-3.56). NLRX1 over-expression (OE) significantly inhibited invasiveness ability and induced apoptosis in hepatocellular carcinoma cells. (PMID:29482578)
• Data show that NLRX1 specifically interacts with FASTKD5 and colocalizes with mitochondrial RNA granules. Further results suggest an important role of NLRX1 in regulating the post-transcriptional processing of mitochondrial RNA, which may have an important implication in bioenergetic adaptation during metabolic stress, oncogenic transformation and innate immunity. (PMID:29932989)
• NLRX1 expression was shown to be associated with angiogenesis, with a significant decrease in NLRX1 expression levels in fresh granulation tissue accompanied by high microvessel density after Negative-Pressure Wound Therapy. (PMID:30141361)
• NLRX1 regulates TNF-alpha-induced mitochondria-lysosomal crosstalk to maintain the invasive and metastatic potential of breast cancer cells. (PMID:30802640)
• mutations associated with multiple sclerosis (PMID:31525189)
• HPV16 drives cancer immune escape via NLRX1-mediated degradation of STING. (PMID:31874109)
• MiR-423-5p Regulates Cells Apoptosis and Extracellular Matrix Degradation via Nucleotide-Binding, Leucine-Rich Repeat Containing X1 (NLRX1) in Interleukin 1 beta (IL-1beta)-Induced Human Nucleus Pulposus Cells. (PMID:32467560)
• MicroRNA-195 suppresses enterovirus A71-induced pyroptosis in human neuroblastoma cells through targeting NLRX1. (PMID:33253716)
• Behind the Scenes: Nod-Like Receptor X1 Controls Inflammation and Metabolism. (PMID:33344269)
• NLRX1 Deletion Increases Ischemia-Reperfusion Damage and Activates Glucose Metabolism in Mouse Heart. (PMID:33362773)
• Focusing on the Cell Type Specific Regulatory Actions of NLRX1. (PMID:33525671)
• Long noncoding RNA NKILA transferred by astrocyte-derived extracellular vesicles protects against neuronal injury by upregulating NLRX1 through binding to mir-195 in traumatic brain injury. (PMID:33686956)
• Macrophage-preferable delivery of the leucine-rich repeat domain of NLRX1 ameliorates lethal sepsis by regulating NF-kappaB and inflammasome signaling activation. (PMID:33971559)
• Nlrx1-Regulated Defense and Metabolic Responses to Aspergillus fumigatus Are Morphotype and Cell Type Specific. (PMID:34790195)
• NLRX1 can counteract innate immune response induced by an external stimulus favoring HBV infection by competitive inhibition of MAVS-RLRs signaling in HepG2-NTCP cells. (PMID:34825857)
• The regulatory role of NLRX1 in innate immunity and human disease. (PMID:36194971)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nlrx1	ENSDARG00000073724
mus_musculus	Nlrx1	ENSMUSG00000032109
rattus_norvegicus	Nlrx1	ENSRNOG00000052386

Paralogs (20): NLRP2 (ENSG00000022556), NLRP1 (ENSG00000091592), NOD1 (ENSG00000106100), NLRC5 (ENSG00000140853), NLRP12 (ENSG00000142405), NLRP14 (ENSG00000158077), NLRP4 (ENSG00000160505), NLRP3 (ENSG00000162711), NOD2 (ENSG00000167207), NLRP7 (ENSG00000167634), NLRC3 (ENSG00000167984), NLRP5 (ENSG00000171487), NLRP13 (ENSG00000173572), NLRP6 (ENSG00000174885), CIITA (ENSG00000179583), NLRP8 (ENSG00000179709), NLRP11 (ENSG00000179873), NLRP10 (ENSG00000182261), NLRP9 (ENSG00000185792), PYDC2 (ENSG00000253548)

Protein

Protein identifiers

NLR family member X1 — Q86UT6 (reviewed: Q86UT6)

Alternative names: Caterpiller protein 11.3, Nucleotide-binding oligomerization domain protein 5, Nucleotide-binding oligomerization domain protein 9

All UniProt accessions (6): Q86UT6, A0A9L9PX86, A0A9L9PXS9, C9J0R6, C9JLK8, C9JQE9

UniProt curated annotations — full annotation on UniProt →

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. Instead, promotes autophagy by interacting with TUFM and subsequently recruiting the autophagy-related proteins ATG5 and ATG12. Also regulates MAVS-dependent NLRP3 inflammasome activation to attenuate apoptosis. 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. Regulates viral mediated-inflammation and energy metabolism in a sex-dependent manner. In females, prevents uncontrolled inflammation and energy metabolism and thus, may contribute to the sex differences observed in infectious and inflammatory diseases.

Subunit / interactions. Homohexamer. Interacts with MAVS. Interacts with TUFM. (Microbial infection) Interacts with influenza A virus protein PB1-F2.

Subcellular location. Mitochondrion outer membrane.

Tissue specificity. Ubiquitously expressed. Strongest expression in mammary gland, heart and muscle. Detected in HeLa, HEK293T, THP-1, HL-60, Raji and Jurkat cell lines (at protein level).

Domain organisation. The LRRCT domain mediates homodimerization and LRRNT mediates trimerization of the dimers.

Similarity. Belongs to the NLRP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86UT6-1	1	yes
Q86UT6-2	2

RefSeq proteins (5): NP_001269072, NP_001269073, NP_001269287, NP_078894, NP_733840 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR007111	NACHT_NTPase	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR048900	NLRX1_C	Domain
IPR051261	NLR	Family

Pfam: PF05729, PF13516, PF21402

UniProt features (46 total): helix 14, repeat 8, strand 8, sequence variant 4, domain 3, region of interest 2, splice variant 2, sequence conflict 2, transit peptide 1, chain 1, binding site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3UN9	X-RAY DIFFRACTION	2.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86UT6-F1	75.01	0.31

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 166–173

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-936440	Negative regulators of DDX58/IFIH1 signaling
R-HSA-9758274	Regulation of NF-kappa B signaling

MSigDB gene sets: 196 (showing top): REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, JAEGER_METASTASIS_DN, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_6_PRODUCTION, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE

GO Biological Process (9): negative regulation of macrophage cytokine production (GO:0010936), negative regulation of interferon-beta production (GO:0032688), negative regulation of interleukin-6 production (GO:0032715), negative regulation of RIG-I signaling pathway (GO:0039536), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), innate immune response (GO:0045087), negative regulation of innate immune response (GO:0045824), negative regulation of inflammatory response (GO:0050728), immune system process (GO:0002376)

GO Molecular Function (3): ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Innate Immune System	1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1
TAK1-dependent IKK and NF-kappa-B activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of defense response	2
negative regulation of response to external stimulus	2
cytoplasm	2
cellular anatomical structure	2
negative regulation of cytokine production involved in immune response	1
macrophage cytokine production	1
regulation of macrophage cytokine production	1
negative regulation of type I interferon production	1
interferon-beta production	1
regulation of interferon-beta production	1
negative regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
RIG-I signaling pathway	1
negative regulation of cytoplasmic pattern recognition receptor signaling pathway	1
regulation of RIG-I signaling pathway	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
immune response	1
defense response to symbiont	1
negative regulation of response to biotic stimulus	1
innate immune response	1
regulation of innate immune response	1
negative regulation of immune response	1
inflammatory response	1
regulation of inflammatory response	1
biological_process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1129 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NLRX1	MAVS	Q7Z434	997
NLRX1	TUFM	P49411	986
NLRX1	TRAF6	Q9Y4K3	956
NLRX1	ATG16L1	Q676U5	949
NLRX1	RIGI	O95786	910
NLRX1	UQCRC2	P22695	909
NLRX1	ATG5	Q9H1Y0	904
NLRX1	ATG12	O94817	862
NLRX1	STING1	Q86WV6	838
NLRX1	IFIH1	Q9BYX4	834
NLRX1	FASTKD5	Q7L8L6	789
NLRX1	EYA4	O95677	789
NLRX1	NLRC4	Q9NPP4	752
NLRX1	TBK1	Q9UHD2	727
NLRX1	IFNB1	P01574	727

IntAct

73 interactions, top by confidence:

A	B	Type	Score
PB2	TUFM	psi-mi:“MI:0914”(association)	0.600
TUFM	PB2	psi-mi:“MI:0914”(association)	0.600
	UBXN8	psi-mi:“MI:0914”(association)	0.530
LPAR4	POTEF	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
VSIG1	TNPO2	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
PVR	ORC4	psi-mi:“MI:0914”(association)	0.530
IL1R2	EXOC5	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
DNAJB8	DNAJB6	psi-mi:“MI:0914”(association)	0.530
TUFM	NLRX1	psi-mi:“MI:0915”(physical association)	0.500
NLRX1	Sarm1	psi-mi:“MI:0915”(physical association)	0.500
NLRX1	MAVS	psi-mi:“MI:0915”(physical association)	0.400
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	DENND11	psi-mi:“MI:0914”(association)	0.350
	BTAF1	psi-mi:“MI:0914”(association)	0.350
MYC	PDZD2	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
HCST	TMEM120B	psi-mi:“MI:0914”(association)	0.350
HIDE1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
OSTM1	ILVBL	psi-mi:“MI:0914”(association)	0.350
GYPA	HYKK	psi-mi:“MI:0914”(association)	0.350
NLGN3	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LRRC25	POTEF	psi-mi:“MI:0914”(association)	0.350
P2RY10	POTEF	psi-mi:“MI:0914”(association)	0.350
DGCR2	CCDC85C	psi-mi:“MI:0914”(association)	0.350

BioGRID (108): NLRX1 (Affinity Capture-MS), NLRX1 (Affinity Capture-MS), NLRX1 (Affinity Capture-MS), NLRX1 (Affinity Capture-MS), NLRX1 (Affinity Capture-MS), NLRX1 (Affinity Capture-MS), NLRX1 (Affinity Capture-MS), NLRX1 (Affinity Capture-MS), NLRX1 (Affinity Capture-MS), NLRX1 (Affinity Capture-MS), BSG (Affinity Capture-MS), NLRX1 (Affinity Capture-MS), NLRX1 (Affinity Capture-MS), NLRX1 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS)

ESM2 similar proteins: A0A061IR73, A0A1B0GUU1, A6H687, A8MYJ7, B1WC39, D3ZVB0, E1BD59, G3MY25, G3MZC5, O75064, P07199, P27790, P29597, P48988, P52333, P52824, Q08DF2, Q0VCE3, Q13608, Q1JPD6, Q2VPB7, Q3TAP4, Q3U1Y4, Q3ZBE0, Q499M4, Q53EQ6, Q5JZY3, Q62137, Q63272, Q6B0B8, Q6DI92, Q6ZPS2, Q6ZS72, Q7TM95, Q80VI1, Q86UT6, Q8BYG9, Q8N9M5, Q8R5G7, Q8TE96

Diamond homologs: Q3TL44, Q5FVQ8, Q86UT6, Q6B966

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
NLRX1	“down-regulates activity”	MAVS	binding
NLRX1	“up-regulates activity”	RELA	relocalization
NLRX1	“up-regulates activity”	PCBP2	binding
NLRX1	“down-regulates activity”	TRAF6	binding
NLRX1	“up-regulates activity”	NfKb-p65/p50	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SLC transporter disorders	5	16.4×	4e-03
Disorders of transmembrane transporters	5	11.2×	6e-03
SLC-mediated transmembrane transport	7	6.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

222 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	168
Likely benign	11
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1885 predictions. Top by Δscore:

Variant	Effect	Δscore
11:119171482:G:GT	donor_gain	1.0000
11:119173473:A:AG	acceptor_gain	1.0000
11:119173477:A:AG	acceptor_gain	1.0000
11:119173477:A:C	acceptor_loss	1.0000
11:119173478:G:GT	acceptor_gain	1.0000
11:119173478:GA:G	acceptor_gain	1.0000
11:119173478:GAA:G	acceptor_gain	1.0000
11:119173478:GAAGC:G	acceptor_gain	1.0000
11:119179687:TTTCA:T	acceptor_loss	1.0000
11:119179688:TTCA:T	acceptor_loss	1.0000
11:119179690:CAGG:C	acceptor_loss	1.0000
11:119179691:A:AG	acceptor_gain	1.0000
11:119179691:AG:A	acceptor_gain	1.0000
11:119179691:AGGT:A	acceptor_gain	1.0000
11:119179691:AGGTG:A	acceptor_gain	1.0000
11:119179692:G:GC	acceptor_loss	1.0000
11:119179692:G:GT	acceptor_gain	1.0000
11:119179692:GG:G	acceptor_gain	1.0000
11:119179692:GGT:G	acceptor_gain	1.0000
11:119179692:GGTG:G	acceptor_gain	1.0000
11:119179692:GGTGG:G	acceptor_gain	1.0000
11:119181152:T:TA	acceptor_gain	1.0000
11:119181153:G:A	acceptor_gain	1.0000
11:119181258:G:GG	donor_gain	1.0000
11:119182186:ACAC:A	acceptor_gain	1.0000
11:119182186:ACACG:A	acceptor_gain	1.0000
11:119182189:C:CA	acceptor_gain	1.0000
11:119182190:G:A	acceptor_gain	1.0000
11:119182343:ACA:A	donor_gain	1.0000
11:119182343:ACAG:A	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000356266 (11:119170429 G>A), RS1000610272 (11:119174267 G>C), RS1000900012 (11:119181015 T>C), RS1001326909 (11:119169183 G>A,C), RS1001727341 (11:119169035 A>G), RS1001935382 (11:119169326 CCTT>C), RS1002024280 (11:119180574 G>A,T), RS1002739788 (11:119171922 T>C), RS1002858427 (11:119166702 C>T), RS1003056725 (11:119172257 C>T), RS1003286007 (11:119182235 C>A,T), RS1003341027 (11:119166381 T>C), RS1003350114 (11:119182988 T>C), RS1003513452 (11:119176885 C>G), RS1003655259 (11:119171007 G>A)

Disease associations

OMIM: gene MIM:611947 | disease phenotypes: MIM:608093, MIM:614750

GenCC curated gene-disease

Mondo (3): long QT syndrome (MONDO:0002442), DPAGT1-congenital disorder of glycosylation (MONDO:0011964), congenital myasthenic syndrome 13 (MONDO:0013883)

Orphanet (3): Congenital myasthenic syndrome with glycosylation defect (Orphanet:353327), Congenital myasthenic syndrome (Orphanet:590), DPAGT1-CDG (Orphanet:86309)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002396_510	Mean reticulocyte volume	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
C535748	Congenital disorder of glycosylation type 1J (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — NOD-like receptor family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
amelenodor	Activation	4.52	pKd

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
sodium arsenite	increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
GSK-J4	decreases expression	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
sodium arsenate	decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
4-phenylenediamine	increases expression	1
mercuric bromide	affects cotreatment, decreases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Bupivacaine	decreases expression, increases reaction, affects reaction, decreases reaction	1
Camptothecin	increases expression	1
Cannabidiol	decreases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Estradiol	affects expression	1
Ethyl Methanesulfonate	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1YP	Abcam HeLa NLRX1 KO	Cancer cell line	Female
CVCL_E0J6	Ubigene HeLa NLRX1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

66 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea