NEURL2

protein-coding

neuralized E3 ubiquitin protein ligase 2

Gene summary

This gene encodes a protein that is involved in the regulation of myofibril organization. This protein is likely the adaptor component of the E3 ubiquitin ligase complex in striated muscle, and it regulates the ubiquitin-mediated degradation of beta-catenin during myogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jun 2013]

Previous symbols:

C20orf163

MANE transcript

NM_080749.4

Inheritance

—

ClinVar variants

U:39B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.93

Max pathogenic AF

—

Genomic locus

chr20:45,888,625-45,891,208

External References & Databases

Ensembl (ENSG00000124257)

Transcript & Mutation Effects

hg38 • Region Span ~2.6 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 NEURL2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 40

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_080749.4. 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						0
missense			39 clinvar	1 clinvar		40
nonsense						0
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)						0
Total	0	0	39	2	0	41

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_080749.4	RefSeq	NP_542787.1	2	MANE Select
ENST00000372518.5	Ensembl	ENSP00000361596.4	2	MANE Select
NM_001278535.2	RefSeq	NP_001265464.1	2	Standard
ENST00000545238.1	Ensembl	ENSP00000442383.1	2	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

protein ubiquitination
intracellular signal transduction
post-translational protein modification

Molecular Function

ubiquitin protein ligase activity

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372518
Coding exons: 2
Length: 2663
Individuals with no LoFs: 124681
Homozygous LoFs: 5
Heterozygous LoFs: 1041
Defined: 125727
p: 0.00417

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.306	158	169	0.934	0.00000803	1794
Missense (PolyPhen)		51	55.076	0.92599		583
Synonymous	-0.690	82	74.4	1.10	0.00000343	643
Loss of Function	0.173	6	6.48	0.926	2.82e-7	66

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0010	0.00092	notable
Latino/Admixed American	0.00099	0.00098	rare
Ashkenazi Jewish	0.0076	0.0075	notable
East Asian	0.000054	0.000054	rare
Finnish	0.0024	0.0024	notable
European (Non-Finnish)	0.0073	0.0071	notable
South Asian	0.0014	0.0014	notable
Other	0.0049	0.0047	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays an important role in the process of myofiber differentiation and maturation. Probable substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex, which mediates the ubiquitination of proteins. Probably contributes to catalysis through recognition and positioning of the substrate and the ubiquitin-conjugating enzyme. During myogenesis, controls the ubiquitination and degradation of the specific pool of CTNNB1/beta-catenin located at the sarcolemma (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.602
RVIS EVS: 0.22
RVIS percentile EVS: 67.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.872

Gene Damage Prediction

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