Amyotrophic lateral sclerosis, susceptibility to, 24

Summary

Amyotrophic lateral sclerosis, susceptibility to, 24 (MONDO:0054750) is a disease caused by NEK1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: NEK1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 31

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amyotrophic lateral sclerosis, susceptibility to, 24
Mondo ID	MONDO:0054750
OMIM	617892
DOID	DOID:0081378
UMLS	C4693523
MedGen	1632999
Is cancer (heuristic)	no

Also known as: ALS24 · amyotrophic lateral sclerosis, susceptibility to, 24

Data availability: 31 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › amyotrophic lateral sclerosis, susceptibility to, 24

Related subtypes (283): microvascular complications of diabetes, susceptibility, Mycobacterium tuberculosis, susceptibility, bacteremia, susceptibility, pregnancy loss, recurrent, susceptibility, autoimmune thyroid disease, susceptibility to, susceptibility to HIV infection, appendicitis, proneness to, atherosclerosis susceptibility, multiple sclerosis, susceptibility to, dyslexia, susceptibility to, 1, endometriosis, susceptibility to, 1, osteoarthritis susceptibility 2, essential hypertension, genetic, osteoarthritis susceptibility 1, otitis media, susceptibility to, pelvic organ prolapse, susceptibility to, pulmonary edema of mountaineers, susceptibility to, sarcoidosis, susceptibility to, 1, strabismus, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 1, predisposition to invasive fungal disease due to CARD9 deficiency, celiac disease, susceptibility to, 1, hemolytic uremic syndrome, atypical, susceptibility to, 1, hypervitaminosis a, susceptibility to, kuru, susceptibility to, leprosy, susceptibility to, 3, nonarteritic anterior ischemic optic neuropathy, susceptibility to, diabetes mellitus, insulin-dependent, X-linked, susceptibility to, coronary heart disease, susceptibility to, 3, dyslexia, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 15, Leber optic atrophy, susceptibility to, dyslexia, susceptibility to, 2, Helicobacter pylori infection, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 1, inherited susceptibility to asthma, renal dysplasia, cystic, susceptibility to, systemic lupus erythematosus, susceptibility to, 1, leishmaniasis, tegumentary, susceptibility to, xanthomatosis, susceptibility to, hyperlipidemia, combined, 1, urinary tract infections, recurrent, susceptibility to, hypertension, essential, susceptibility to, 1, hepatic fibrosis, severe, susceptibility to, due to Schistosoma mansoni infection, dyslexia, susceptibility to, 3, Ascaris lumbricoides infection, susceptibility to, hypertension, essential, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 3, nephrolithiasis, uric acid, susceptibility to, atrioventricular septal defect, susceptibility to, 2, vitiligo-associated multiple autoimmune disease susceptibility 1, polysubstance abuse, susceptibility to, dyslexia, susceptibility to, 6, glaucoma, normal tension, susceptibility to, anorexia nervosa, susceptibility to, 1, stroke, susceptibility to, 1, dyslexia, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 2, familial meningioma, celiac disease, susceptibility to, 5, systemic lupus erythematosus with hemolytic anemia, susceptibility to, 1, hypertension, essential, susceptibility to, 3, coronary heart disease, susceptibility to, 1, bulimia nervosa, susceptibility to, 1, leprosy, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 9, Parkinson disease 11, autosomal dominant, susceptibility to, focal segmental glomerulosclerosis 3, susceptibility to, autoimmune disease, susceptibility to, 1, osteoarthritis susceptibility 3, systemic lupus erythematosus with nephritis, susceptibility to, 1, systemic lupus erythematosus with nephritis, susceptibility to, 2, systemic lupus erythematosus with nephritis, susceptibility to, 3, coronary heart disease, susceptibility to, 2, coronary heart disease, susceptibility to, 4, autoimmune disease, susceptibility to, 2, autoimmune disease, susceptibility to, 3, systemic lupus erythematosus, susceptibility to, 4, myocardial infarction, susceptibility to, major depressive disorder 1, legionnaire disease, susceptibility to, myocardial infarction, susceptibility to, 2, major depressive disorder 2, hypertension, essential, susceptibility to, 4, epilepsy, idiopathic generalized, susceptibility to, 3, myoclonic epilepsy, juvenile, susceptibility to, 3, orofacial cleft 6, susceptibility to, coronary heart disease, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 1, attention deficit-hyperactivity disorder, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 3, attention deficit-hyperactivity disorder, susceptibility to, 4, Alzheimer disease 9, susceptibility to respiratory infections associated with CD8alpha chain mutation, dyslexia, susceptibility to, 8, autoimmune disease, susceptibility to, 4, hepatitis C virus, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 4, celiac disease, susceptibility to, 4, celiac disease, susceptibility to, 2, celiac disease, susceptibility to, 3, leprosy, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 5, systemic lupus erythematosus, susceptibility to, 6, opioid dependence, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 8, hypertension, essential, susceptibility to, 5, hypertension, essential, susceptibility to, 6, Parkinson disease 13, autosomal dominant, susceptibility to, West Nile virus, susceptibility to, hepatitis B virus, susceptibility to, Buruli ulcer, susceptibility to, osteoarthritis susceptibility 4, systemic lupus erythematosus, susceptibility to, 9, coronary heart disease, susceptibility to, 7, hypertension, essential, susceptibility to, 7, leprosy, susceptibility to, 4, hypertension, essential, susceptibility to, 8, epilepsy, idiopathic generalized, susceptibility to, 13, coronary heart disease, susceptibility to, 8, myoclonic epilepsy, juvenile, susceptibility to, 4, susceptibility to visceral leishmaniasis, 2, susceptibility to visceral leishmaniasis, 3, celiac disease, susceptibility to, 6, epilepsy, idiopathic generalized, susceptibility to, 5, epilepsy, childhood absence, susceptibility to, 6, celiac disease, susceptibility to, 7, celiac disease, susceptibility to, 8, celiac disease, susceptibility to, 9, celiac disease, susceptibility to, 10, celiac disease, susceptibility to, 11, celiac disease, susceptibility to, 12, celiac disease, susceptibility to, 13, coronary heart disease, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 10, systemic lupus erythematosus, susceptibility to, 11, systemic lupus erythematosus, susceptibility to, 12, epilepsy, childhood absence, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 6, systemic lupus erythematosus, susceptibility to, 13, sarcoidosis, susceptibility to, 2, sarcoidosis, susceptibility to, 3, osteoarthritis susceptibility 5, osteoarthritis susceptibility 6, focal segmental glomerulosclerosis 4, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 8, herpes simplex encephalitis, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 10, pelvic organ prolapse, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 14, leprosy, susceptibility to, 5, thyrotoxic periodic paralysis, susceptibility to, 2, hearing loss, cisplatin-induced, susceptibility to, susceptibility to mononeuropathy of the median nerve, mild, fatty liver disease, nonalcoholic, susceptibility to, 2, leprosy, susceptibility to, 6, autoimmune disease, susceptibility to, 6, Parkinson disease 5, autosomal dominant, susceptibility to, aspergillosis, susceptibility to, sick sinus syndrome 3, susceptibility to, Parkinson disease 18, autosomal dominant, susceptibility to, epilepsy, juvenile myoclonic, susceptibility to, 9, dengue virus, susceptibility to, coronary heart disease, susceptibility to, 6, podoconiosis, susceptibility to, peripartum cardiomyopathy, susceptibility to, influenza, severe, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 3, human herpesvirus 8, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 12, herpes simplex encephalitis, susceptibility to, 3, herpes simplex encephalitis, susceptibility to, 4, pulmonary hypertension, neonatal, susceptibility to, craniosynostosis 5, susceptibility to, melioidosis, susceptibility to, chronic mountain sickness, susceptibility to, herpes simplex encephalitis, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 14, hereditary neoplastic syndrome, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency, susceptibility to localized juvenile periodontitis, inherited susceptibility to mycobacterial diseases, neural tube defects, susceptibility to, multiple system atrophy 1, susceptibility to, nephrolithiasis susceptibility caused by SLC26A1, myoclonic epilepsy, juvenile, susceptibility to, 1, epilepsy, childhood absence, susceptibility to, 1, autism, susceptiblity to, susceptibility to visceral leishmaniasis, 1, malaria, susceptibility to, spondyloarthropathy, susceptibility to, herpes simplex encephalitis, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 18, epilepsy, idiopathic generalized, susceptibility to, 15, hepatitis, fulminant viral, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 16, autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial jak1 deficiency, aortic aneurysm, familial thoracic 11, susceptibility to, craniosynostosis 7, amyotrophic lateral sclerosis, susceptibility to, 25, epilepsy, juvenile myoclonic, susceptibility to, 10, susceptibility to angioedema induced by ACE inhibitors, epidermodysplasia verruciformis, susceptibility to, exfoliation syndrome, susceptibility to, basal cell carcinoma, susceptibility to, graft-versus-host disease, susceptibility to, narcolepsy, susceptibility to, pulmonary disease, chronic obstructive, susceptibility to, restless legs syndrome, susceptibility to, psoriasis, susceptibility to, age related macular degeneration, susceptibility to, allergic rhinitis, susceptibility to, dermatitis, atopic, susceptibility to, Hirschsprung disease, susceptibility to, diabetes mellitus, ketosis-prone, schizophrenia, susceptibility to, radioulnar synostosis, nonsyndromic, susceptibility to, lumbar disk herniation, susceptibility to, lumbar disk degeneration, susceptibility to, psoriatic arthritis, susceptibility to, migraine with or without aura, susceptibility to, Alzheimer disease, susceptibility to, mitochondrial, Asperger syndrome, susceptibility to, tobacco addiction, susceptibility to, lipodystrophy, partial, acquired, susceptibility to, Graves disease, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 17, breast-ovarian cancer, familial, susceptibility to, blepharospasm, benign essential, susceptibility to, hemorrhage, intracerebral, susceptibility to, IgA nephropathy, susceptibility to, hemolytic uremic syndrome, atypical, susceptibility to, 7, vitiligo-associated multiple autoimmune disease susceptibility 6, delayed sleep phase syndrome, susceptibility to, encephalitis, acute, infection-induced, susceptibility to, malignant hyperthermia, susceptibility to, multicentric Castleman disease, susceptibility to, pelvic organ prolapse, susceptibility to, 1, amyotrophic lateral sclerosis, susceptibility to, 13, Graves disease, susceptibility to, X-linked 2, autoimmune thyroid disease, susceptibility to, 5, atrioventricular septal defect, susceptibility to, 1, epilepsy, juvenile myoclonic, susceptibility to, 6, autoimmune disease, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 6, seasonal affective disorder, susceptibility to, ventricular fibrillation during myocardial infarction, susceptibility to, UV-induced skin damage, susceptibility to, antisocial behavior, susceptibility to, aplastic anemia, susceptibility to, cardiomyopathy, familial hypertrophic, 4, susceptibility to, cirrhosis, noncryptogenic, susceptibility to, coronary artery disease, severe, susceptibility to, dengue fever, susceptibility to, dengue hemorrhagic fever, susceptibility to, dengue shock syndrome, susceptibility to, dyslexia, susceptibility to, 4, dyslexia, susceptibility to, 7, efavirenz central nervous system toxicity, susceptibility to, obesity, susceptibility to, bleeding disorder, platelet-type, 13, susceptibility to, Schistosoma mansoni infection, susceptibility/resistance to, Parkinson disease 24, autosomal dominant, susceptibility to, iron overload, susceptibility to, hydrocephalus, congenital, 5, susceptibility to, hearing loss, noise-induced, susceptibility to, hyperemesis gravidarum, susceptibility to, Parkinson disease 26, autosomal dominant, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 19, polycystic kidney disease 9, susceptibility to, rhabdomyolysis, susceptibility to, scoliosis, isolated, susceptibility to, dystonia 38, susceptibility to, gallbladder disease 4, epilepsy, juvenile absence, susceptibility to, GBA1-related Parkinson disease, susceptibility, SH2B3-related immune system disorder

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

31 retrieved; paginated sample, class counts are floors:

9 likely pathogenic, 8 uncertain significance, 6 conflicting classifications of pathogenicity, 4 pathogenic, 1 pathogenic/likely pathogenic, 1 benign/likely benign, 1 risk factor, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
431443	NM_000207.3(INS):c.-152C>G	INS	Pathogenic	criteria provided, multiple submitters, no conflicts
1332832	NM_001199397.3(NEK1):c.1957C>T (p.Arg653Ter)	NEK1	Pathogenic	criteria provided, multiple submitters, no conflicts
208600	NM_001199397.3(NEK1):c.3107C>G (p.Ser1036Ter)	NEK1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4819004	NM_001199397.3(NEK1):c.2231T>G (p.Leu744Ter)	NEK1	Pathogenic	criteria provided, single submitter
495120	NM_001199397.3(NEK1):c.1648C>T (p.Arg550Ter)	NEK1	Pathogenic	criteria provided, single submitter
1474082	NM_001199397.3(NEK1):c.2588-2A>G	NEK1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2583154	NM_001199397.3(NEK1):c.1324C>T (p.Gln442Ter)	NEK1	Likely pathogenic	criteria provided, single submitter
3024566	NM_001199397.3(NEK1):c.1804C>T (p.Gln602Ter)	NEK1	Likely pathogenic	criteria provided, single submitter
3242535	NM_001199397.3(NEK1):c.1414C>T (p.Arg472Ter)	NEK1	Likely pathogenic	criteria provided, single submitter
3382213	NM_001199397.3(NEK1):c.1739_1740del (p.Lys580fs)	NEK1	Likely pathogenic	criteria provided, single submitter
3383149	NM_001199397.3(NEK1):c.2640del (p.Val881fs)	NEK1	Likely pathogenic	criteria provided, single submitter
348106	NM_001199397.3(NEK1):c.2282_2283del (p.Leu760_Ser761insTer)	NEK1	Likely pathogenic	criteria provided, single submitter
4687928	NM_001199397.3(NEK1):c.1467T>G (p.Tyr489Ter)	NEK1	Likely pathogenic	criteria provided, single submitter
992988	NM_001199397.3(NEK1):c.2539G>T (p.Glu847Ter)	NEK1	Likely pathogenic	criteria provided, single submitter
495118	NM_001199397.3(NEK1):c.2434A>T (p.Arg812Ter)	NEK1	risk factor	no assertion criteria provided
199125	NM_001199397.3(NEK1):c.782G>A (p.Arg261His)	NEK1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
266047	NM_001199397.3(NEK1):c.1137T>A (p.Asp379Glu)	NEK1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
266048	NM_001199397.3(NEK1):c.1789T>A (p.Phe597Ile)	NEK1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
282693	NM_001199397.3(NEK1):c.2361G>A (p.Lys787=)	NEK1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
348122	NM_001199397.3(NEK1):c.642G>A (p.Lys214=)	NEK1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
446674	NM_001199397.3(NEK1):c.418G>A (p.Gly140Arg)	NEK1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1328972	NM_001199397.3(NEK1):c.3838T>C (p.Tyr1280His)	NEK1	Uncertain significance	criteria provided, single submitter
1493572	NM_001199397.3(NEK1):c.3437G>A (p.Arg1146Lys)	NEK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3391231	NM_001199397.3(NEK1):c.2771A>T (p.Asp924Val)	NEK1	Uncertain significance	criteria provided, single submitter
3590450	NM_001199397.3(NEK1):c.1267G>A (p.Ala423Thr)	NEK1	Uncertain significance	criteria provided, single submitter
3891824	NM_001199397.3(NEK1):c.2590A>G (p.Ile864Val)	NEK1	Uncertain significance	criteria provided, single submitter
578956	NM_001199397.3(NEK1):c.1925C>G (p.Ala642Gly)	NEK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
811174	NM_001199397.3(NEK1):c.2400G>C (p.Glu800Asp)	NEK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
900737	NM_001199397.3(NEK1):c.1080G>C (p.Glu360Asp)	NEK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
283728	NM_001199397.3(NEK1):c.3213C>T (p.Asn1071=)	NEK1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
NEK1	Definitive	Autosomal dominant	amyotrophic lateral sclerosis, susceptibility to, 24	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NEK1	Orphanet:2751	Orofaciodigital syndrome type 2
NEK1	Orphanet:803	Amyotrophic lateral sclerosis
NEK1	Orphanet:93269	Short rib-polydactyly syndrome, Majewski type
INS	Orphanet:552	MODY
INS	Orphanet:99885	Isolated permanent neonatal diabetes mellitus

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NEK1	HGNC:7744	ENSG00000137601	Q96PY6	Serine/threonine-protein kinase Nek1	gencc,clinvar
INS	HGNC:6081	ENSG00000254647	P01308	Insulin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NEK1	Serine/threonine-protein kinase Nek1	Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity.
INS	Insulin	Insulin decreases blood glucose concentration.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NEK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
INS	Other/Unknown	no		Insulin, Insulin-like, Ins/IGF/rlx

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
secondary oocyte	1
trigeminal ganglion	1
body of pancreas	1
islet of Langerhans	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NEK1	288	ubiquitous	marker	secondary oocyte, trigeminal ganglion, oocyte
INS	137	tissue_specific	marker	type B pancreatic cell, islet of Langerhans, body of pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
INS	11,670
NEK1	1,512

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
INS	P01308	382
NEK1	Q96PY6	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 39. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
IRS activation	1	1142.0×	0.015	INS
Signal attenuation	1	519.1×	0.015	INS
Signaling by Insulin receptor	1	439.2×	0.015	INS
Regulation of beta-cell development	1	356.9×	0.015	INS
Insulin receptor signalling cascade	1	335.9×	0.015	INS
Synthesis, secretion, and deacylation of Ghrelin	1	300.5×	0.015	INS
Transcriptional Regulation by NPAS4	1	285.5×	0.015	INS
Regulation of pyruvate metabolism	1	285.5×	0.015	NEK1
Regulation of gene expression in beta cells	1	259.6×	0.015	INS
NPAS4 regulates expression of target genes	1	248.3×	0.015	INS
Insulin processing	1	228.4×	0.015	INS
Pyruvate metabolism	1	203.9×	0.015	NEK1
Insulin receptor recycling	1	190.3×	0.015	INS
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1	190.3×	0.015	INS
FOXO-mediated transcription	1	167.9×	0.015	INS
Negative regulation of the PI3K/AKT network	1	139.3×	0.016	INS
Peptide hormone metabolism	1	135.9×	0.016	INS
Metabolism	2	11.6×	0.016	NEK1, INS
Regulation of insulin secretion	1	109.8×	0.019	INS
Integration of energy metabolism	1	87.8×	0.022	INS
ER to Golgi Anterograde Transport	1	66.4×	0.028	INS
COPI-mediated anterograde transport	1	54.9×	0.031	INS
Transport to the Golgi and subsequent modification	1	51.4×	0.031	INS
Amyloid fiber formation	1	51.4×	0.031	INS
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	48.4×	0.032	INS
Intracellular signaling by second messengers	1	45.7×	0.032	INS
Aerobic respiration and respiratory electron transport	1	44.3×	0.032	NEK1
PIP3 activates AKT signaling	1	33.4×	0.041	INS
Asparagine N-linked glycosylation	1	30.1×	0.044	INS
Signaling by Receptor Tyrosine Kinases	1	25.8×	0.050	INS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of glycogen catabolic process	1	4213.0×	0.004	INS
positive regulation of nitric-oxide synthase activity	1	2808.7×	0.004	INS
obsolete positive regulation of nitric oxide mediated signal transduction	1	2106.5×	0.004	INS
negative regulation of fatty acid metabolic process	1	2106.5×	0.004	INS
negative regulation of feeding behavior	1	2106.5×	0.004	INS
alpha-beta T cell activation	1	1685.2×	0.004	INS
negative regulation of respiratory burst involved in inflammatory response	1	1685.2×	0.004	INS
positive regulation of respiratory burst	1	1685.2×	0.004	INS
positive regulation of dendritic spine maintenance	1	1685.2×	0.004	INS
negative regulation of acute inflammatory response	1	1203.7×	0.005	INS
nitric oxide-cGMP-mediated signaling	1	766.0×	0.006	INS
regulation of protein secretion	1	766.0×	0.006	INS
positive regulation of peptide hormone secretion	1	766.0×	0.006	INS
neuron projection maintenance	1	561.7×	0.006	INS
positive regulation of glycogen biosynthetic process	1	495.6×	0.006	INS
positive regulation of brown fat cell differentiation	1	495.6×	0.006	INS
negative regulation of reactive oxygen species biosynthetic process	1	495.6×	0.006	INS
fatty acid homeostasis	1	468.1×	0.006	INS
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	1	468.1×	0.006	INS
positive regulation of lipid biosynthetic process	1	443.5×	0.006	INS
negative regulation of protein secretion	1	443.5×	0.006	INS
positive regulation of insulin receptor signaling pathway	1	421.3×	0.006	INS
negative regulation of lipid catabolic process	1	421.3×	0.006	INS
negative regulation of gluconeogenesis	1	401.2×	0.006	INS
positive regulation of glycolytic process	1	337.0×	0.007	INS
positive regulation of long-term synaptic potentiation	1	337.0×	0.007	INS
regulation of protein localization to plasma membrane	1	324.1×	0.007	INS
positive regulation of mitotic nuclear division	1	271.8×	0.008	INS
positive regulation of D-glucose import across plasma membrane	1	227.7×	0.009	INS
acute-phase response	1	210.7×	0.009	INS

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
NEK1	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NEK1	12	4
INS	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	NEK1
DABRAFENIB	4	NEK1
LESTAURTINIB	3	NEK1
TG100-115	2	NEK1
R-406	2	NEK1
PELITINIB	2	NEK1
GSK-461364	1	NEK1
KW-2449	1	NEK1
AMG-900	1	NEK1
TAK-593	1	NEK1
CYC-116	1	NEK1
AST-487	1	NEK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
NEK1	288	Binding:288
INS	8	Binding:7, ADMET:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
NEK1	288

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

12 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	NEK1
DABRAFENIB	4	NEK1
LESTAURTINIB	3	NEK1
TG100-115	2	NEK1
R-406	2	NEK1
PELITINIB	2	NEK1
GSK-461364	1	NEK1
KW-2449	1	NEK1
AMG-900	1	NEK1
TAK-593	1	NEK1
CYC-116	1	NEK1
AST-487	1	NEK1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	NEK1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	INS

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
INS	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.