NELL1

protein-coding

neural EGFL like 1

Gene summary

This gene encodes a cytoplasmic protein that contains epidermal growth factor (EGF)-like repeats. The encoded heterotrimeric protein may be involved in cell growth regulation and differentiation. A similar protein in rodents is involved in craniosynostosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

MANE transcript

NM_006157.5

Inheritance

—

ClinVar variants

U:121B:17

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.54

Max pathogenic AF

—

Genomic locus

chr11:20,669,551-21,575,686

External References & Databases

Ensembl (ENSG00000165973)

Transcript & Mutation Effects

hg38 • Region Span ~906.1 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 NELL1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 120

not providedTotal: 17

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006157.5. 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			1 clinvar	4 clinvar	2 clinvar	7
missense			119 clinvar	3 clinvar	8 clinvar	130
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	121	7	10	138

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006157.5	RefSeq	NP_006148.2	20	MANE Select
ENST00000357134.10	Ensembl	ENSP00000349654.5	20	MANE Select
NM_001288713.1	RefSeq	NP_001275642.1	21	Standard
NM_001288714.1	RefSeq	NP_001275643.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

nervous system development
regulation of gene expression
cell differentiation
positive regulation of bone mineralization
negative regulation of osteoblast proliferation

Molecular Function

calcium ion binding
protein binding

Cellular Component

extracellular region
nuclear envelope
cytoplasm
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357134
Coding exons: 20
Length: 906111
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 50
Defined: 125748
p: 0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.00549	454	454	1.00	0.0000236	5356
Missense (PolyPhen)		121	158.61	0.76288		1923
Synonymous	-0.765	172	160	1.08	0.00000852	1449
Loss of Function	2.95	26	48.1	0.541	0.00000260	575

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00036	0.00036	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the control of cell growth and differentiation. Promotes osteoblast cell differentiation and terminal mineralization. {ECO:0000269|PubMed:21723284}.;

Recessive Scores

pRec: 0.148

Intolerance Scores

LoFtool: 0.295
RVIS EVS: 0.21
RVIS percentile EVS: 67.52

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.448

Gene Damage Prediction

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