NUB1

protein-coding

negative regulator of ubiquitin like proteins 1

Gene summary

This gene encodes a protein that functions as a negative regulator of NEDD8, a ubiquitin-like protein that conjugates with cullin family members in order to regulate vital biological events. The protein encoded by this gene regulates the NEDD8 conjugation system post-transcriptionally by recruiting NEDD8 and its conjugates to the proteasome for degradation. This protein interacts with the product of the AIPL1 gene, which is associated with Leber congenital amaurosis, an inherited retinopathy, and mutations in that gene can abolish interaction with this protein, which may contribute to the pathogenesis. This protein is also known to accumulate in Lewy bodies in Parkinson's disease and dementia with Lewy bodies, and in glial cytoplasmic inclusions in multiple system atrophy, with this abnormal accumulation being specific to alpha-synucleinopathy lesions. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

MANE transcript

NM_001243351.2

Inheritance

—

ClinVar variants

U:34B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr7:151,341,772-151,378,449

External References & Databases

Ensembl (ENSG00000013374)

Transcript & Mutation Effects

hg38 • Region Span ~36.7 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 NUB1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 19

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001243351.2. 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			2 clinvar	1 clinvar		3
missense			24 clinvar		1 clinvar	25
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	34	1	1	36

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 99 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001243351.2	RefSeq	NP_001230280.2	14	MANE Select
ENST00000568733.6	Ensembl	ENSP00000454264.2	14	MANE Select
NM_001363529.2	RefSeq	NP_001350458.1	14	Standard
NM_001385353.1	RefSeq	NP_001372282.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Neddylation

Biological Process

ubiquitin-dependent protein catabolic process
protein ubiquitination
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
response to interferon-gamma
response to tumor necrosis factor

Molecular Function

protein binding

Cellular Component

nucleus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000568733
Coding exons: 15
Length: 36751
Individuals with no LoFs: 124611
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 124646
p: 0.000140

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.36	263	333	0.790	0.0000186	4139
Missense (PolyPhen)		77	112.88	0.68217		1370
Synonymous	0.619	127	136	0.933	0.00000871	1173
Loss of Function	3.44	12	33.5	0.358	0.00000166	455

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00027	0.00026	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00028	0.00028	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00013	0.00013	rare
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Specific down-regulator of the NEDD8 conjugation system. Recruits NEDD8, UBD, and their conjugates to the proteasome for degradation. Isoform 1 promotes the degradation of NEDD8 more efficiently than isoform 2. {ECO:0000269|PubMed:16707496}.;

Recessive Scores

pRec: 0.118

Intolerance Scores

RVIS EVS: -0.33
RVIS percentile EVS: 30.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.732

Gene Damage Prediction

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