NBR1

protein-coding

NBR1 autophagy cargo receptor, the group of Zinc fingers ZZ-type

Gene summary

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. [provided by RefSeq, Apr 2014]

Previous symbols:

M17S2

MANE transcript

NM_005899.5

Inheritance

—

ClinVar variants

U:107B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr17:43,170,481-43,211,689

External References & Databases

Ensembl (ENSG00000188554)

Transcript & Mutation Effects

hg38 • Region Span ~41.2 kb

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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 NBR1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 93

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005899.5. 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			2 clinvar	1 clinvar	3 clinvar	6
missense			99 clinvar	4 clinvar	1 clinvar	104
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	107	5	4	116

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 80 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005899.5	RefSeq	NP_005890.2	20	MANE Select
ENST00000590996.6	Ensembl	ENSP00000466667.1	20	MANE Select
NM_001291571.2	RefSeq	NP_001278500.1	20	Standard
NM_001291572.2	RefSeq	NP_001278501.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mitophagy - animal - Homo sapiens (human)

Biological Process

macroautophagy
regulation of bone mineralization
regulation of stress-activated MAPK cascade
negative regulation of osteoblast differentiation
protein complex oligomerization

Molecular Function

protein binding
zinc ion binding
ubiquitin binding
mitogen-activated protein kinase binding

Cellular Component

phagophore assembly site
nucleoplasm
mitochondrion
lysosome
late endosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000422280
Coding exons: 20
Length: 41211
Individuals with no LoFs: 124620
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 124657
p: 0.000148

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.36	402	487	0.826	0.0000239	6290
Missense (PolyPhen)		113	173.01	0.65313		2197
Synonymous	2.40	138	179	0.771	0.00000881	1854
Loss of Function	3.50	22	48.2	0.456	0.00000247	599

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00050	0.00050	rare
Finnish	0.00019	0.00019	rare
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.00018	0.00016	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts probably as a receptor for selective autophagosomal degradation of ubiquitinated targets. {ECO:0000269|PubMed:19250911}.;

Intolerance Scores

LoFtool: 0.796
RVIS EVS: 0.87
RVIS percentile EVS: 88.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.981

Gene Damage Prediction

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