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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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NELL1
neural EGFL like 1
Chromosome 11 · 11p15.1
NCBI Gene: 4745Ensembl: ENSG00000165973.19HGNC: HGNC:7750UniProt: B3KXR2
88PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingpositive regulation of osteoblast differentiationperinuclear region of cytoplasmnuclear envelopetype 2 diabetes mellitussmoking initiationautoimmune thyroid diseasesubarachnoid hemorrhage
✦AI Summary

NELL1 (neural epidermal growth factor-like 1) is a secreted protein that plays dual roles in bone biology and immune-mediated kidney disease. In bone, NELL1 promotes osteoblast differentiation and terminal mineralization while negatively regulating osteoblast proliferation [UniProt annotation]. However, NELL1 has gained clinical significance as a target autoantigen in membranous nephropathy (MN), an autoimmune kidney disease causing nephrotic syndrome in adults. In primary MN, circulating IgG autoantibodies against NELL1 form immune complexes that deposit along the glomerular basement membrane in a granular pattern, with NELL1 and IgG co-localizing on electron microscopy 1. NELL1-associated MN accounts for 5-10% of PLA2R- and THSD7A-negative cases 2, making it the second most common identified antigen after PLA2R 3. This subset exhibits distinctive clinical features of primary MN and is associated with malignancy, specific medications, and mercury exposure 3. Predominantly IgG1 and IgG4 anti-NELL1 antibodies can be detected via ELISA and immunofluorescence assays with high specificity (94.9%-100%) 3. Clinical recognition of NELL1-positive MN is critical, as accurate antigen identification guides treatment decisions and prognosis monitoring in this previously uncharacterized MN subset 4.

Sources cited
1
NELL1 co-localizes with IgG along the glomerular basement membrane in membranous nephropathy and defines a distinct type of primary MN with anti-NELL1 antibodies detectable in patient sera
PMID: 31901340
2
NELL1 is associated with 5-10% of primary MN cases that are PLA2R- and THSD7A-negative
PMID: 33808418
3
Anti-NELL1 antibodies in patient sera are predominantly IgG1 and IgG4; ELISA and immunofluorescence assays for detection have high specificity (94.9%-100%); NELL1-associated MN is associated with malignancy, certain medications, and mercury poisoning
PMID: 40541723
4
NELL1 is among newly discovered target antigens with distinctive clinical and pathologic findings and therapeutic implications in membranous nephropathy
PMID: 37863839
5
NELL1 displays a risk effect for nonischemic cardiomyopathy with increased expression in hypertrophic cardiomyopathy
PMID: 39267096
Disease Associationsⓘ20
type 2 diabetes mellitusOpen Targets
0.35Weak
smoking initiationOpen Targets
0.31Weak
autoimmune thyroid diseaseOpen Targets
0.29Weak
subarachnoid hemorrhageOpen Targets
0.28Weak
adolescent idiopathic scoliosisOpen Targets
0.28Weak
Hodgkins lymphomaOpen Targets
0.28Weak
drug allergyOpen Targets
0.28Weak
macular degenerationOpen Targets
0.28Weak
malunion fractureOpen Targets
0.28Weak
peritonitisOpen Targets
0.28Weak
respiratory system diseaseOpen Targets
0.27Weak
alopecia areataOpen Targets
0.26Weak
spinal cord injuryOpen Targets
0.26Weak
preeclampsiaOpen Targets
0.25Weak
blood coagulation diseaseOpen Targets
0.25Weak
HirsutismOpen Targets
0.25Weak
intestinal impactionOpen Targets
0.25Weak
placental retentionOpen Targets
0.25Weak
HypercholesterolemiaOpen Targets
0.24Weak
injuryOpen Targets
0.24Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ROBO3Protein interaction93%ANO6Protein interaction90%ANO5Protein interaction87%THSD7AProtein interaction82%PLA2R1Protein interaction61%ATRAIDShared pathway56%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
0%
Ovary
0%
Lung
0%
Heart
0%
Liver
0%
Gene Interaction Network
Click a node to explore
NELL1ROBO3ANO6ANO5THSD7APLA2R1ATRAID
PROTEIN STRUCTURE
Preparing viewer…
PDB6POL · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.83LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.67 [0.54–0.83]
RankingsWhere NELL1 stands among ~20K protein-coding genes
  • #5,429of 20,598
    Most Researched88
  • #7,023of 17,882
    Most Constrained (LOEUF)0.83
Genes detectedNELL1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Membranous Nephropathy: Core Curriculum 2021.
PMID: 33487481
Am J Kidney Dis · 2021
1.00
2
Mechanisms of Primary Membranous Nephropathy.
PMID: 33808418
Biomolecules · 2021
0.90
3
New 'Antigens' in Membranous Nephropathy.
PMID: 33380523
J Am Soc Nephrol · 2021
0.80
4
Antigens in membranous nephropathy: discovery and clinical implications.
PMID: 40691733
Nat Rev Nephrol · 2025
0.70
5
Membranous nephropathy-diagnosis and identification of target antigens.
PMID: 37863839
Nephrol Dial Transplant · 2024
0.60