NEURL4

protein-coding

neuralized E3 ubiquitin protein ligase 4

Gene summary

The protein encoded by this gene is predicted and it includes two isoforms resulting from two alternatively spliced transcript variants. [provided by RefSeq, Jul 2008]

MANE transcript

NM_032442.3

Inheritance

—

ClinVar variants

U:220B:21

Top phenotype

NEURL4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr17:7,315,628-7,329,393

External References & Databases

Ensembl (ENSG00000215041)

Transcript & Mutation Effects

hg38 • Region Span ~13.8 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 NEURL4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 202

not providedTotal: 23

NEURL4-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032442.3. 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			3 clinvar	7 clinvar	4 clinvar	14
missense			208 clinvar	9 clinvar	1 clinvar	218
nonsense						0
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	220	16	5	241

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032442.3	RefSeq	NP_115818.2	29	MANE Select
ENST00000399464.7	Ensembl	ENSP00000382390.2	29	MANE Select
NM_001005408.2	RefSeq	NP_001005408.1	29	Standard
ENST00000315614.11	Ensembl	ENSP00000319826.7	29	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding
ubiquitin protein ligase activity

Cellular Component

centriole

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000399464
Coding exons: 29
Length: 13766
Individuals with no LoFs: 124826
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 124841
p: 0.0000601

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.95	732	994	0.737	0.0000644	10038
Missense (PolyPhen)		182	314.72	0.57829		3029
Synonymous	0.107	416	419	0.993	0.0000282	3364
Loss of Function	6.72	8	67.6	0.118	0.00000350	723

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000064	0.000062	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Promotes CCP110 ubiquitination and proteasome-dependent degradation. By counteracting accumulation of CP110, maintains normal centriolar homeostasis and preventing formation of ectopic microtubular organizing centers. {ECO:0000269|PubMed:22261722, ECO:0000269|PubMed:22441691}.;

Intolerance Scores

LoFtool: 0.272
RVIS EVS: -0.18
RVIS percentile EVS: 39.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.587

Gene Damage Prediction

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