NBR1

Summary

NBR1 (NBR1 autophagy cargo receptor, HGNC:6746) is a protein-coding gene on chromosome 17q21.31, encoding Next to BRCA1 gene 1 protein (Q14596). Ubiquitin-binding autophagy adapter that participates in different processes including host defense or intracellular homeostasis.

The protein encoded by this gene was originally identified as an ovarian tumor antigen monitored in ovarian cancer. The encoded protein contains a B-box/coiled-coil motif, which is present in many genes with transformation potential. It functions as a specific autophagy receptor for the selective autophagic degradation of peroxisomes by forming intracellular inclusions with ubiquitylated autophagic substrates. This gene is located on a region of chromosome 17q21.1 that is in close proximity to the BRCA1 tumor suppressor gene. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 4077 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 168 total
• MANE Select transcript: NM_005899

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6746
Approved symbol	NBR1
Name	NBR1 autophagy cargo receptor
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	CA125, KIAA0049, 1A1-3B
Ensembl gene	ENSG00000188554
Ensembl biotype	protein_coding
OMIM	166945
Entrez	4077

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 28 protein_coding, 2 retained_intron

ENST00000341165, ENST00000542611, ENST00000585505, ENST00000586650, ENST00000589872, ENST00000590996, ENST00000592304, ENST00000902839, ENST00000902840, ENST00000902841, ENST00000902842, ENST00000928838, ENST00000955656, ENST00000955657, ENST00000955658, ENST00000955659, ENST00000955660, ENST00000955661, ENST00000955662, ENST00000955663, ENST00000955664, ENST00000955665, ENST00000955666, ENST00000955667, ENST00000955668, ENST00000955669, ENST00000955670, ENST00000955671, ENST00000955672, ENST00000955673

RefSeq mRNA: 4 — MANE Select: NM_005899 NM_001291571, NM_001291572, NM_005899, NM_031862

CCDS: CCDS45694, CCDS77037, CCDS77038

Canonical transcript exons

ENST00000590996 — 21 exons

Exon	Start	End
ENSE00001365287	43189588	43189802
ENSE00001374892	43190609	43190776
ENSE00001379068	43186250	43186444
ENSE00001390001	43189042	43189119
ENSE00001611511	43201686	43201780
ENSE00001619731	43194964	43195039
ENSE00001640806	43194350	43194499
ENSE00001663596	43202655	43202712
ENSE00001703728	43203681	43203786
ENSE00001706048	43200167	43200608
ENSE00001730522	43196481	43196591
ENSE00001767543	43196942	43197106
ENSE00002338781	43177936	43177998
ENSE00002366424	43179394	43179412
ENSE00002388501	43180795	43180817
ENSE00002695056	43175791	43175901
ENSE00002785844	43209901	43211688
ENSE00002831146	43171214	43171302
ENSE00003599986	43191372	43191581
ENSE00003600056	43193348	43193638
ENSE00003663605	43193094	43193253

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.8598 / max 323.4279, expressed in 1820 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161059	47.1070	1819
161058	3.2838	1351
161056	0.9377	670
161057	0.4870	264
161062	0.0194	5
161060	0.0156	6
161061	0.0094	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.62	gold quality
amniotic fluid	UBERON:0000173	98.44	gold quality
parietal pleura	UBERON:0002400	97.98	gold quality
epithelium of nasopharynx	UBERON:0001951	97.96	gold quality
germinal epithelium of ovary	UBERON:0001304	97.94	gold quality
choroid plexus epithelium	UBERON:0003911	97.79	gold quality
medial globus pallidus	UBERON:0002477	97.72	gold quality
pleura	UBERON:0000977	97.63	gold quality
jejunal mucosa	UBERON:0000399	97.59	gold quality
globus pallidus	UBERON:0001875	97.49	gold quality
palpebral conjunctiva	UBERON:0001812	97.39	gold quality
visceral pleura	UBERON:0002401	97.34	gold quality
tendon	UBERON:0000043	97.25	gold quality
right testis	UBERON:0004534	97.25	gold quality
gluteal muscle	UBERON:0002000	97.19	gold quality
left testis	UBERON:0004533	97.11	gold quality
tibia	UBERON:0000979	97.10	gold quality
nephron tubule	UBERON:0001231	97.07	gold quality
jejunum	UBERON:0002115	96.98	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.94	gold quality
sperm	CL:0000019	96.90	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.80	gold quality
parotid gland	UBERON:0001831	96.65	gold quality
male germ cell	CL:0000015	96.62	gold quality
rectum	UBERON:0001052	96.62	gold quality
corpus callosum	UBERON:0002336	96.58	gold quality
bronchial epithelial cell	CL:0002328	96.48	gold quality
calcaneal tendon	UBERON:0003701	96.42	gold quality
gastrocnemius	UBERON:0001388	96.40	gold quality
muscle of leg	UBERON:0001383	96.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.41

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HAND2

miRNA regulators (miRDB)

79 targeting NBR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-609	99.82	64.26	505
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093

Literature-anchored findings (GeneRIF, showing 25)

• interacts with two proteins; fasciculation and elongation protein zeta-1 (FEZ1), a PKCzeta interacting protein, and calcium and integrin binding protein (CIB), also shows developmentally restricted expression in the neural tube (PMID:11856312)
• NBR1 together with p62 promotes autophagic degradation of ubiquitinated targets and simultaneously regulates their aggregation when autophagy becomes limited. (PMID:19398892)
• The nbr1 UBA domain binds to lysine-48 and -63 linked polyubiquitin-B chains. Nbr1 also binds to the autophagic effector protein LC3-A via a novel binding site. (PMID:19427866)
• findings suggest a critical function for NBR1 in the regulation of receptor trafficking and provide a mechanism for down-regulation of signaling by Spred2 via NBR1. (PMID:19822672)
• The structural ensemble representing each of the two sequential folding transition transition states of the PB1 domain of NBR1 has been calculated using experimental Phi values and biased molecular dynamics simulations. (PMID:21121670)
• AtNBR1 is more similar to mammalian NBR1 than to p62 in domain architecture and amino acid sequence. (PMID:21606687)
• Results indicate that the presence of a tryptophan residue in the LIR motif increases the binding affinity of GABARAPL-1/NBR1-LIR complex. (PMID:21620860)
• Breast and ovarian cancer risk are high in Jewish women with BRCA1 genetic mutation. (PMID:22430266)
• These findings suggest that NBR1 is involved in the formation of cytoplasmic inclusions in alpha-synucleinopathy. (PMID:22484440)
• Autophagy-related NBR1 protein is not involved in the formation/degradation of neuronal intranuclear inclusions in neurodegenerative diseases. (PMID:22728060)
• results suggest that NBR1 is the specific autophagy receptor for pexophagy. (PMID:23239026)
• structure of the ubiquitin-associated (UBA) domain of human autophagy receptor NBR1 and its interaction with ubiquitin and polyubiquitin (PMID:24692539)
• The C-terminal fragments of SQSTM1 and NBR1 exhibited a dominant-negative effect against native SQSTM1/NBR1, probably by competing for LC3 and ubiquitin chain binding. (PMID:24769734)
• Analysis of muscle biopsies of sporadic inclusion body myositis (sIBM) patients revealed a strong decrease of NBR1 phosphorylation in muscles of sIBM patients that directly correlated with the severity of protein aggregation. (PMID:24879152)
• NBR1 positively correlates with adipose inflammation in human obese patients. (PMID:25043814)
• NBR1 is not required for PARK2-dependent mitophagy. (PMID:26512954)
• The NBR1 depletion impairs FA turnover and decreases targeting of autophagosomes to FAs, whereas ectopic expression of autophagy-competent, but not autophagy-defective, NBR1 enhances FA disassembly and reduces FA lifetime during migration. (PMID:26903539)
• Depletion of NBR1 in urothelial carcinoma cells enhances rapamycin-induced apoptosis through impaired autophagy and mitochondrial dysfunction. (PMID:31297862)
• The influence of rs139416141 in neighbor of Brca1 gene (NBR1) on bone mineral density in postmenopausal Chinese women. (PMID:32577726)
• Identification of putative phenotype-modifying genetic factors associated with phenotypic diversity in Brooke-Spiegler syndrome. (PMID:32744342)
• An increase in p62/NBR1 levels in melioidosis patients of Sri Lanka exhibit a characteristic of potential host biomarker. (PMID:32815800)
• Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation. (PMID:34471133)
• Germline mutation in the NBR1 gene involved in autophagy detected in a family with renal tumors. (PMID:34488032)
• NBR1 mediates autophagic degradation of IRF3 to negatively regulate type I interferon production. (PMID:35914352)
• NBR1-mediated autophagic degradation of caspase 8 protects vascular endothelial cells against arsenite-induced apoptotic cell death. (PMID:38678786)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nbr1a	ENSDARG00000077297
danio_rerio	nbr1b	ENSDARG00000078772
mus_musculus	Nbr1	ENSMUSG00000017119
rattus_norvegicus	Nbr1	ENSRNOG00000020730

Protein

Protein identifiers

Next to BRCA1 gene 1 protein — Q14596 (reviewed: Q14596)

Alternative names: Cell migration-inducing gene 19 protein, Membrane component chromosome 17 surface marker 2, Neighbor of BRCA1 gene 1 protein, Protein 1A1-3B

All UniProt accessions (3): A0A0C4DGP6, B7Z5R6, Q14596

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitin-binding autophagy adapter that participates in different processes including host defense or intracellular homeostasis. Possesses a double function during the selective autophagy by acting as a shuttle bringing ubiquitinated proteins to autophagosomes and also by participating in the formation of protein aggregates. Plays a role in the regulation of the innate immune response by modulating type I interferon production and targeting ubiquitinated IRF3 for autophagic degradation. In response to oxidative stress, promotes an increase in SQSTM1 levels, phosphorylation, and body formation by preventing its autophagic degradation. In turn, activates the KEAP1-NRF2/NFE2L2 antioxidant pathway. Also plays non-autophagy role by mediating the shuttle of IL-12 to late endosome for subsequent secretion.

Subunit / interactions. Homooligomer and heterooligomer. Interacts with TRIM55. Interacts with titin/TTN. Interacts with RNF29, USP8, MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAP, GABARAPL1 and GABARAPL2. Binds to ubiquitin and ubiquitinated proteins. Interacts with SQSTM1. Interacts with TAX1BP1. Interacts with IRF3; this interaction mediates autophagic degradation of IRF3. Interacts with IL12A and IL12B. Interacts with SRBD1; this interaction clears SRBD1 through the autophagic-lysosomal pathway. (Microbial infection) Interacts with Influenza A virus protein PB1; this interaction promotes NBR1-mediated selective autophagic degradation of MAVS.

Subcellular location. Cytoplasm. Cytoplasmic vesicle. Autophagosome. Lysosome. Myofibril. Sarcomere. M line.

Post-translational modifications. (Microbial infection) Cleaved by S.pyogenes SpeB protease; leading to its degradation. Degradation by SpeB prevents autophagy, promoting to S.pyogenes intracellular replication. Phosphorylated by GSK3A; this phosphorylation inhibits NBR1 involvement in the formation of ubiquitinated protein aggregates.

Domain organisation. The PB1 domain mediates interaction with SQSTM1.

Induction. Upon viral infection.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14596-1	1	yes
Q14596-2	2

RefSeq proteins (4): NP_001278500, NP_001278501, NP_005890, NP_114068 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000270	PB1_dom	Domain
IPR000433	Znf_ZZ	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015940	UBA	Domain
IPR032350	Nbr1_FW	Domain
IPR034852	PB1_Nbr1	Domain
IPR043145	Znf_ZZ_sf	Homologous_superfamily
IPR053793	PB1-like	Domain
IPR056893	UBA_Nbr1_C	Domain

Pfam: PF00564, PF00569, PF16158, PF24932

UniProt features (56 total): strand 14, binding site 8, mutagenesis site 7, helix 7, modified residue 5, region of interest 5, domain 2, turn 2, chain 1, splice variant 1, sequence variant 1, zinc finger region 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
2BKF	X-RAY DIFFRACTION	1.56
2G4S	X-RAY DIFFRACTION	2.15
4OLE	X-RAY DIFFRACTION	2.52
1WJ6	SOLUTION NMR
2CP8	SOLUTION NMR
2L8J	SOLUTION NMR
2MGW	SOLUTION NMR
2MJ5	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14596-F1	59.56	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 (8): 217; 220; 231; 234; 240; 243; 250; 254

Post-translational modifications (5): 116, 586, 590, 596, 625

Mutagenesis-validated functional residues (7):

Position	Phenotype
12	no effect on interaction with sqstm1.
50	loss of interaction with sqstm1.
586	loss of phosphorylation by gsk3a.
732	loss of interaction atg8 family proteins.
926	about 3-fold weaker interaction with ubiquitin than wt.
928	about 2-fold weaker interaction with ubiquitin than wt.
929	complete loss of interaction with ubiquitin.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9664873	Pexophagy
R-HSA-1632852	Macroautophagy
R-HSA-9612973	Autophagy
R-HSA-9663891	Selective autophagy

MSigDB gene sets: 236 (showing top): GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_MACROAUTOPHAGY, WANG_LMO4_TARGETS_DN, GOBP_BONE_MINERALIZATION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_OSSIFICATION, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOBP_REGULATION_OF_OSTEOBLAST_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS, GOCC_MICROBODY_MEMBRANE, GOBP_NEGATIVE_REGULATION_OF_OSTEOBLAST_DIFFERENTIATION, DANG_BOUND_BY_MYC

GO Biological Process (4): macroautophagy (GO:0016236), regulation of bone mineralization (GO:0030500), regulation of stress-activated MAPK cascade (GO:0032872), negative regulation of osteoblast differentiation (GO:0045668)

GO Molecular Function (5): zinc ion binding (GO:0008270), ubiquitin binding (GO:0043130), mitogen-activated protein kinase binding (GO:0051019), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (16): phagophore assembly site (GO:0000407), nucleoplasm (GO:0005654), mitochondrial intermembrane space (GO:0005758), lysosome (GO:0005764), late endosome (GO:0005770), autophagosome (GO:0005776), peroxisomal membrane (GO:0005778), cytosol (GO:0005829), membrane (GO:0016020), nuclear body (GO:0016604), M band (GO:0031430), signaling receptor complex (GO:0043235), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytoplasmic vesicle (GO:0031410), intracellular organelle lumen (GO:0070013)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Selective autophagy	1
Autophagy	1
Macroautophagy	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	4
autophagosome assembly	1
autophagy	1
regulation of ossification	1
bone mineralization	1
regulation of biomineral tissue development	1
regulation of MAPK cascade	1
stress-activated MAPK cascade	1
regulation of stress-activated protein kinase signaling cascade	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
transition metal ion binding	1
ubiquitin-like protein binding	1
protein kinase binding	1
binding	1
cation binding	1
nuclear lumen	1
mitochondrial envelope	1
organelle envelope lumen	1
lytic vacuole	1
endosome	1
vacuole	1
peroxisome	1
microbody membrane	1
nucleoplasm	1
intracellular membraneless organelle	1
A band	1
protein-containing complex	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
intracellular vesicle	1
intracellular organelle	1
organelle lumen	1

Protein interactions and networks

STRING

2425 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NBR1	GABARAPL2	P60520	997
NBR1	F5GZY7	F5GZY7	997
NBR1	GABARAP	O95166	996
NBR1	SQSTM1	Q13501	985
NBR1	TTN	Q8WZ42	981
NBR1	OPTN	Q96CV9	947
NBR1	CALCOCO2	Q13137	939
NBR1	CD300C	Q08708	921
NBR1	PEX5	P50542	919
NBR1	ATG12	O94817	906
NBR1	TRIM63	Q969Q1	902
NBR1	MAP1LC3B	Q9GZQ8	902
NBR1	ATG16L1	Q676U5	858
NBR1	RB1CC1	Q8TDY2	851
NBR1	WDFY3	Q8IZQ1	829
NBR1	BNIP3L	O60238	829

IntAct

141 interactions, top by confidence:

A	B	Type	Score
JUNB	FOS	psi-mi:“MI:0914”(association)	0.950
SQSTM1	PRKCI	psi-mi:“MI:0914”(association)	0.890
GSK3A	NBR1	psi-mi:“MI:0915”(physical association)	0.840
GSK3A	NBR1	psi-mi:“MI:0217”(phosphorylation reaction)	0.840
NBR1	GSK3A	psi-mi:“MI:0915”(physical association)	0.840
GSK3A	AXIN1	psi-mi:“MI:0914”(association)	0.800
GABARAP	NBR1	psi-mi:“MI:0915”(physical association)	0.780
NBR1	GABARAP	psi-mi:“MI:0407”(direct interaction)	0.780
GABARAP	NBR1	psi-mi:“MI:0407”(direct interaction)	0.780
SQSTM1	NBR1	psi-mi:“MI:0915”(physical association)	0.770
MAP1LC3B	NBR1	psi-mi:“MI:0915”(physical association)	0.770
NBR1	SQSTM1	psi-mi:“MI:0403”(colocalization)	0.770
NBR1	MAP1LC3B	psi-mi:“MI:0915”(physical association)	0.770
MAP1LC3B	NBR1	psi-mi:“MI:0407”(direct interaction)	0.770
NBR1	MAP1LC3B	psi-mi:“MI:0407”(direct interaction)	0.770
NBR1	SQSTM1	psi-mi:“MI:0915”(physical association)	0.770
MAP1LC3B	NBR1	psi-mi:“MI:0403”(colocalization)	0.770
SQSTM1	NBR1	psi-mi:“MI:0403”(colocalization)	0.770
HTT	SQSTM1	psi-mi:“MI:0403”(colocalization)	0.770
ATP5IF1	ATP5F1B	psi-mi:“MI:0914”(association)	0.740
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730

BioGRID (495): SYT4 (Two-hybrid), SQSTM1 (Reconstituted Complex), UBC (Reconstituted Complex), MAP1LC3B (Reconstituted Complex), GABARAP (Reconstituted Complex), UBC (Reconstituted Complex), UBC (Affinity Capture-Western), NBR1 (Affinity Capture-MS), NBR1 (Affinity Capture-MS), VTA1 (Two-hybrid), NBR1 (Affinity Capture-MS), NBR1 (Affinity Capture-Western), NBR1 (Affinity Capture-Western), MAP2K4 (Affinity Capture-Western), MAP3K3 (Affinity Capture-Western)

ESM2 similar proteins: A0A1L8GR68, A2CG63, E9Q9M8, F7AQ22, G3V8T1, O75152, O75376, P49140, P51826, P97432, Q13625, Q14596, Q17R98, Q1LY51, Q3TYA6, Q4KKX4, Q4LE39, Q4R6F6, Q501R9, Q505G8, Q5F3Z9, Q5HYC2, Q5RC94, Q5XJV7, Q60974, Q68FE8, Q69Z61, Q6A098, Q6NXK2, Q6NZF1, Q6PJT7, Q6ZNC4, Q86YI8, Q8BFU3, Q8BJ05, Q8CCH7, Q8CG79, Q8CHY6, Q8K2W6, Q8ND24

Diamond homologs: M1BJF6, P97432, Q14596, Q3TT38, Q501R9, Q5BL31, Q5F3N9, Q5RC94, Q9H6K1, Q9SB64, O08623, O95714, P14199, Q13501, Q24629, Q4U2R1, Q5RBA5, Q64337, Q68LP1, Q8R516, Q96AX9, Q9P792, Q5ZIJ9, Q6GNY1, Q804S5, Q80SY4, Q86YT6, Q9VUX2, A2CI98, Q1LZE1, Q6GPB6, Q7T321, Q80UY2, Q95RX5, Q9P0J7

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
MAP1LC3B	down-regulates	NBR1	binding
MAP1LC3C	down-regulates	NBR1	binding
NBR1	up-regulates	GABARAP	binding
NBR1	up-regulates	GABARAPL1	binding
NBR1	up-regulates	GABARAPL2	binding
NBR1	up-regulates	MAP1LC3A	binding
NBR1	up-regulates	SQSTM1	binding
GSK3A	“down-regulates activity”	NBR1	phosphorylation
GSK3B	“down-regulates activity”	NBR1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 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
PINK1-PRKN Mediated Mitophagy	5	27.4×	1e-04
Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A	5	15.7×	8e-04
Signaling by ALK fusions and activated point mutants	6	13.9×	4e-04
Degradation of beta-catenin by the destruction complex	5	13.3×	1e-03
Macroautophagy	7	12.4×	1e-04
KEAP1-NFE2L2 pathway	6	11.1×	8e-04
Cargo recognition for clathrin-mediated endocytosis	6	9.7×	1e-03
Interleukin-1 signaling	5	9.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	8	29.2×	1e-07
autophagosome maturation	6	24.2×	3e-05
macroautophagy	7	19.4×	2e-05
autophagosome assembly	6	15.5×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	119
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3083 predictions. Top by Δscore:

Variant	Effect	Δscore
17:43175771:A:AG	acceptor_gain	1.0000
17:43175772:C:G	acceptor_gain	1.0000
17:43175774:A:AG	acceptor_gain	1.0000
17:43175775:A:G	acceptor_gain	1.0000
17:43175789:A:AG	acceptor_gain	1.0000
17:43175790:G:GG	acceptor_gain	1.0000
17:43186233:ATAAT:A	acceptor_gain	1.0000
17:43186234:T:G	acceptor_gain	1.0000
17:43186235:A:AG	acceptor_gain	1.0000
17:43186235:AAT:A	acceptor_gain	1.0000
17:43186444:GGTA:G	donor_loss	1.0000
17:43186445:G:GC	donor_loss	1.0000
17:43186446:T:G	donor_loss	1.0000
17:43189040:A:AG	acceptor_gain	1.0000
17:43189040:AGTC:A	acceptor_gain	1.0000
17:43189041:G:GG	acceptor_gain	1.0000
17:43189041:GT:G	acceptor_gain	1.0000
17:43189041:GTC:G	acceptor_gain	1.0000
17:43189041:GTCG:G	acceptor_gain	1.0000
17:43189041:GTCGT:G	acceptor_gain	1.0000
17:43189043:C:A	acceptor_gain	1.0000
17:43189116:GACG:G	donor_gain	1.0000
17:43189118:CGGTG:C	donor_loss	1.0000
17:43189119:GGTG:G	donor_loss	1.0000
17:43189120:G:GG	donor_gain	1.0000
17:43189120:G:T	donor_loss	1.0000
17:43189585:TAGTT:T	acceptor_loss	1.0000
17:43189586:A:AG	acceptor_gain	1.0000
17:43189586:AGT:A	acceptor_loss	1.0000
17:43189587:G:GA	acceptor_gain	1.0000

AlphaMissense

6354 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:43193202:A:C	K394N	1.000
17:43193202:A:T	K394N	1.000
17:43193206:T:A	W396R	1.000
17:43193206:T:C	W396R	1.000
17:43193207:G:C	W396S	1.000
17:43193208:G:C	W396C	1.000
17:43193208:G:T	W396C	1.000
17:43193236:T:A	W406R	1.000
17:43193236:T:C	W406R	1.000
17:43193489:T:A	W459R	1.000
17:43193489:T:C	W459R	1.000
17:43193531:T:A	W473R	1.000
17:43193531:T:C	W473R	1.000
17:43194976:T:C	F563L	1.000
17:43194978:T:A	F563L	1.000
17:43194978:T:G	F563L	1.000
17:43194983:T:C	L565P	1.000
17:43189798:T:C	C231R	0.999
17:43191443:G:C	R312P	0.999
17:43191448:G:C	A314P	0.999
17:43191464:T:C	L319P	0.999
17:43193195:T:C	F392S	0.999
17:43193200:A:G	K394E	0.999
17:43193220:T:A	N400K	0.999
17:43193220:T:G	N400K	0.999
17:43193238:G:C	W406C	0.999
17:43193238:G:T	W406C	0.999
17:43193349:T:C	L412P	0.999
17:43193360:T:A	W416R	0.999
17:43193360:T:C	W416R	0.999

dbSNP variants (sampled 300 via entrez): RS1000049412 (17:43182501 A>G), RS1000162940 (17:43209529 A>G), RS1000172817 (17:43197983 C>T), RS1000326278 (17:43190961 A>G), RS1000345962 (17:43170561 A>C), RS1000480487 (17:43183589 C>T), RS1000535817 (17:43188056 AT>A,ATT), RS1000547859 (17:43182857 A>C), RS1000639524 (17:43209331 C>T), RS1000643586 (17:43188590 T>C), RS1000697589 (17:43202406 C>T), RS1000729635 (17:43202183 A>AAG), RS1000800587 (17:43170235 T>C,G), RS1000831563 (17:43174672 G>A), RS1000882225 (17:43174377 C>T)

Disease associations

OMIM: gene MIM:166945 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	4
sodium arsenite	affects reaction, increases cleavage, decreases reaction, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
FR900359	decreases phosphorylation	1
arsenite	affects binding, decreases reaction	1
zinc chromate	increases abundance, increases expression	1
lei gong teng	increases expression	1
epigallocatechin gallate	increases expression	1
polyhexamethyleneguanidine	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
corosolic acid	increases expression	1
K 7174	increases expression	1
abrine	increases expression	1
apilimod	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, increases expression	1
jinfukang	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Zoledronic Acid	increases expression	1
Air Pollutants	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	decreases ubiquitination	1
Vehicle Emissions	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Cisplatin	decreases expression, decreases reaction	1
Cycloheximide	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Estradiol	decreases expression	1
Ethinyl Estradiol	decreases expression	1

Cellosaurus cell lines

13 cell lines: 12 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7YE	Abcam Raji NBR1 KO	Cancer cell line	Male
CVCL_B9Z3	Abcam THP-1 NBR1 KO	Cancer cell line	Male
CVCL_C2VN	HeLa S3 penta KO	Cancer cell line	Female
CVCL_C2VP	HeLa S3 penta KO-ATG13 KO	Cancer cell line	Female
CVCL_C2VQ	HeLa S3 penta KO-ATG14 KO	Cancer cell line	Female
CVCL_C2VR	HeLa S3 penta KO-TBK1 KO	Cancer cell line	Female
CVCL_C2VS	HeLa S3 penta KO-ULK1/ULK2 DKO	Cancer cell line	Female
CVCL_C2VT	HeLa S3 penta KO-TBK1/ULK1/ULK2 TKO	Cancer cell line	Female
CVCL_C7AT	Abcam PC-3 NBR1 KO	Cancer cell line	Male
CVCL_C8QB	HeLa S3 penta KO-AZI2/TBKBP1 DKO clone 20	Cancer cell line	Female

Clinical trials (associated diseases)

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