CausalSentinel

Protein Dossier — NELL1 (Protein kinase C-binding protein NELL1)

MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).

1. Published MR estimates (retrieved, not computed)

Outcome	beta	se	p	method	nSNP	cis/trans	coloc
Diagnoses - main ICD10: R14 Flatulence and related conditions	0.423	0.127	8.87e-04	Inverse variance weighted	2	cis	NA
Diagnoses - main ICD10: R14 Flatulence and related conditions	0.423	0.127	8.87e-04	Inverse variance weighted	2	trans	NA
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal	0.104	0.0349	0.00288	Inverse variance weighted	2	cis	NA
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal	0.104	0.0349	0.00288	Inverse variance weighted	2	trans	NA
Potassium in urine	-0.0127	0.00465	0.00649	Inverse variance weighted	2	cis	NA
Potassium in urine	-0.0127	0.00465	0.00649	Inverse variance weighted	2	trans	NA
Alcohol intake frequency	0.0176	0.00678	0.00942	Inverse variance weighted	2	cis	NA
Alcohol intake frequency	0.0176	0.00678	0.00942	Inverse variance weighted	2	trans	NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast	-0.1	0.0397	0.0117	Inverse variance weighted	2	cis	NA
Diagnoses - main ICD10: C50 Malignant neoplasm of breast	-0.1	0.0397	0.0117	Inverse variance weighted	2	trans	NA
Schizophrenia	-0.043	0.0194	0.0269	Inverse variance weighted	2	cis	NA
Schizophrenia	-0.043	0.0194	0.0269	Inverse variance weighted	2	trans	NA
…and 177 more outcomes (see JSON)

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

3. GWAS Catalog results — traits with signal at this locus

105 association rows across 76 traits (53 genome-wide significant rows). Associations are loci, not causal claims; the mapped gene at a locus is not necessarily the effector gene.

Trait	best p	lead SNP	n assoc	study	MR status
ERBB4/NELL1 protein level ratio	7e-664	rs8176786	1	GCST90314691	no MR -> candidate analysis
Protein kinase C-binding protein NELL1 levels	3e-256	rs61652119	4	GCST90248637	no MR -> candidate analysis
NELL1 protein levels	1e-134	rs1949523	10	GCST90470026	no MR -> candidate analysis
Serum levels of protein FAM189A2	4e-122	rs8176786	2	GCST90089155	no MR -> candidate analysis
Serum levels of protein NELL1	2e-115	rs8176786	1	GCST90089486	no MR -> candidate analysis
Protein kinase C-binding protein NELL1 levels (NELL1.6544.33	1e-89	rs61652119	1	GCST90242481	no MR -> candidate analysis
Blood protein levels	9e-79	rs16907058	2	GCST006585	no MR -> candidate analysis
Protein FAM189A2 (analyte X5699.19) levels	1e-57	rs8176786	1	GCST90426460	no MR -> candidate analysis
Protein FAM189A2 levels (FAM189A2.5699.19.3)	7e-49	rs8176786	1	GCST90242459	no MR -> candidate analysis
Cerebrospinal fluid protein NELL1 levels	1e-36	rs79474191	1	GCST90944453	no MR -> candidate analysis
Core binding factor acute myeloid leukemia	6e-20	rs7119634; rs10500896; rs4576820; rs10833472; rs1377744; rs4923393; rs7948285; rs11025959; rs1945321; rs4412753	2	GCST008413	no MR -> candidate analysis
NELL2 protein levels	6e-16	rs111992703	2	GCST90470027	no MR -> candidate analysis
…and 64 more traits (see JSON)

4. Phenome map — where this gene is a genetic locus, vs. where MR exists

Top diseases by Open Targets association (of 2547 total). Associations are loci, not causal claims. The causal-status column is a four-state triage per pair: established (curated) = a curated clinical assertion exists (ClinGen/G2P/GEL/Orphanet/ClinVar — any validity level, MR adds little); exploratory rare-variant signal = ExWAS burden evidence without curation — a candidate NEW gene-disease relationship; common-variant locus = GWAS signal, classic pQTL-MR territory; multi-layer = burden+GWAS together, an allelic-series candidate (the strongest causal setup). Burden estimand is carrier-vs-noncarrier, not per-SD MR.

Disease	genetic assoc.	burden (ExWAS)	causal status	MR status
type 2 diabetes mellitus	0.551	—	common-variant locus	no MR -> candidate analysis
smoking initiation	0.519	—	common-variant locus	no MR -> candidate analysis
spinal cord injury	0.431	—	common-variant locus	no MR -> candidate analysis
alopecia areata	0.431	—	common-variant locus	no MR -> candidate analysis
respiratory system disorder	0.427	—	common-variant locus	no MR -> candidate analysis
subarachnoid hemorrhage	0.417	—	common-variant locus	no MR -> candidate analysis
adolescent idiopathic scoliosis	0.409	—	common-variant locus	no MR -> candidate analysis
Hodgkins lymphoma	0.406	—	common-variant locus	no MR -> candidate analysis
intestinal impaction	0.406	—	common-variant locus	no MR -> candidate analysis
drug allergy	0.406	—	common-variant locus	no MR -> candidate analysis
Hirsutism	0.406	—	common-variant locus	no MR -> candidate analysis
peritonitis	0.406	—	common-variant locus	no MR -> candidate analysis
blood coagulation disease	0.406	—	common-variant locus	no MR -> candidate analysis
macular degeneration	0.406	—	common-variant locus	no MR -> candidate analysis
digestive system disorder	0.406	—	common-variant locus	no MR -> candidate analysis

Of the 15 rows above, 15 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 0 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.

5. Downstream annotation (druggability & safety preview)

Layer	Result
ChEMBL druggability	not available — no ChEMBL target (undrugged)
gnomAD constraint	pLI=3.2e-18, LOEUF=0.856 — LoF-tolerant
GWAS Catalog	119 unique SNPs / 264 rows
ClinVar	172 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx	no annotations

Caveats declared by the tools

• phenome — Top 30 of 2547 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.
• chembl — No ChEMBL target for ‘NELL1’.
• clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 172 ClinVar records for this gene; it is a sample, not a rate.
• pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).
• gwas_traits — Top 20 of 76 traits by best p-value, aggregated from 105 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.

Sources

• uniprot: https://www.uniprot.org/uniprotkb/Q92832 — UniProt release 2026_02 (10-June-2026)
• mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0
• phenome: https://platform.opentargets.org/target/ENSG00000165973/associations — Open Targets data release 26.06
• gnomad: https://gnomad.broadinstitute.org/gene/NELL1 — gnomAD constraint via GraphQL API (reference genome GRCh38)
• gwas: https://www.ebi.ac.uk/gwas/genes/NELL1 — GWAS Catalog REST (live; release not exposed by this endpoint)
• clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=NELL1%5Bgene%5D — ClinVar build Build260809-1055.1
• gwas_traits: https://www.ebi.ac.uk/gwas/genes/NELL1 — GWAS Catalog search API (live; release not exposed)

Provenance

• Generated: 2026-08-14T03:57:41 · Tier: A
• Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
• MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
• Tool errors this run: none

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