Lipodystrophy, partial, acquired, susceptibility to

Summary

Lipodystrophy, partial, acquired, susceptibility to (MONDO:0100476) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 579

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lipodystrophy, partial, acquired, susceptibility to
Mondo ID	MONDO:0100476
OMIM	608709
UMLS	C3887501
MedGen	854363
Is cancer (heuristic)	no

Also known as: APLD, susceptibility to · barraquer-simons syndrome · lipodystrophy, cephalothoracic type · lipodystrophy, partial, acquired, susceptibility · lipodystrophy, partial, progressive

Data availability: 579 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › lipodystrophy, partial, acquired, susceptibility to

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, 24, 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, 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

579 retrieved; paginated sample, class counts are floors:

257 uncertain significance, 257 likely benign, 30 benign, 26 conflicting classifications of pathogenicity, 9 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1053135	NM_032737.4(LMNB2):c.1016A>C (p.Glu339Ala)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1113094	NM_032737.4(LMNB2):c.999T>G (p.Asp333Glu)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1396806	NM_032737.4(LMNB2):c.698C>T (p.Thr233Met)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1413080	NM_032737.4(LMNB2):c.1475C>T (p.Ser492Leu)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1473987	NM_032737.4(LMNB2):c.395A>G (p.Asn132Ser)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1644524	NM_032737.4(LMNB2):c.1535A>G (p.Glu512Gly)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1649494	NM_032737.4(LMNB2):c.750G>C (p.Gln250His)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1665539	NM_032737.4(LMNB2):c.1852T>C (p.Tyr618His)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2064424	NM_032737.4(LMNB2):c.1744G>A (p.Val582Met)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2100666	NM_032737.4(LMNB2):c.1677C>G (p.Ser559Arg)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
445837	NM_032737.4(LMNB2):c.265-19C>T	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
475775	NM_032737.4(LMNB2):c.1403C>G (p.Ala468Gly)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
542428	NM_032737.4(LMNB2):c.700C>T (p.Arg234Trp)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
542437	NM_032737.4(LMNB2):c.574G>T (p.Ala192Ser)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
542438	NM_032737.4(LMNB2):c.1312C>T (p.Arg438Trp)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
576766	NM_032737.4(LMNB2):c.1298G>A (p.Arg433His)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
578090	NM_032737.4(LMNB2):c.512G>A (p.Arg171His)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
644388	NM_032737.4(LMNB2):c.1057C>A (p.Leu353Met)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
647572	NM_032737.4(LMNB2):c.1750C>T (p.Arg584Cys)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
652532	NM_032737.4(LMNB2):c.281C>T (p.Ala94Val)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
660656	NM_032737.4(LMNB2):c.1553C>T (p.Thr518Met)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
772460	NM_032737.4(LMNB2):c.1796G>A (p.Gly599Asp)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
804992	NM_032737.4(LMNB2):c.1063G>A (p.Ala355Thr)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
845810	NM_032737.4(LMNB2):c.1232G>A (p.Arg411His)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
859972	NM_032737.4(LMNB2):c.757G>A (p.Asp253Asn)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
965151	NM_032737.4(LMNB2):c.1406C>T (p.Ser469Leu)	LMNB2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2427064	NC_000019.9:g.(?1456055)(2456931_?)dup	ABHD17A	Uncertain significance	criteria provided, single submitter
3248492	NC_000019.9:g.(?2430909)(3121177_?)dup	DIRAS1	Uncertain significance	criteria provided, single submitter
1002507	NM_032737.4(LMNB2):c.481G>C (p.Val161Leu)	LMNB2	Uncertain significance	criteria provided, single submitter
1010809	NM_032737.4(LMNB2):c.335G>A (p.Arg112Gln)	LMNB2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 2 · 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
LMNB2	Limited	Autosomal dominant	lipodystrophy, partial, acquired, susceptibility to	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LMNB2	Orphanet:457265	Progressive myoclonic epilepsy type 9
LMNB2	Orphanet:79087	Acquired partial lipodystrophy

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LMNB2	HGNC:6638	ENSG00000176619	Q03252	Lamin-B2	gencc,clinvar
DIRAS1	HGNC:19127	ENSG00000176490	O95057	GTP-binding protein Di-Ras1	clinvar
ABHD17A	HGNC:28756	ENSG00000129968	Q96GS6	Alpha/beta hydrolase domain-containing protein 17A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LMNB2	Lamin-B2	Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane.
DIRAS1	GTP-binding protein Di-Ras1	Displays low GTPase activity and exists predominantly in the GTP-bound form.
ABHD17A	Alpha/beta hydrolase domain-containing protein 17A	Hydrolyzes fatty acids from S-acylated cysteine residues in proteins.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.0

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
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LMNB2	Other/Unknown	no		Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf
DIRAS1	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
ABHD17A	Other/Unknown	no		ABHD17C-like, AB_hydrolase_fold

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	1
right testis	1
ventricular zone	1
apex of heart	1
left ventricle myocardium	1
right frontal lobe	1
Ammon’s horn	1
granulocyte	1
primary visual cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LMNB2	194	ubiquitous	marker	ventricular zone, left testis, right testis
DIRAS1	196	ubiquitous	yes	left ventricle myocardium, apex of heart, right frontal lobe
ABHD17A	139	ubiquitous	marker	granulocyte, primary visual cortex, Ammon’s horn

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LMNB2	3,562
DIRAS1	2,973
ABHD17A	752

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LMNB2	Q03252	2
DIRAS1	O95057	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ABHD17A	Q96GS6	89.99

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 3 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RAS processing	1	475.8×	0.011	ABHD17A
MAPK1/MAPK3 signaling	1	131.3×	0.016	ABHD17A
MAPK family signaling cascades	1	102.9×	0.016	ABHD17A
RAF/MAP kinase cascade	1	61.1×	0.020	ABHD17A
Signal Transduction	1	10.2×	0.098	ABHD17A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of protein localization to endosome	1	1872.4×	0.003	ABHD17A
nuclear pore localization	1	1123.5×	0.003	LMNB2
negative regulation of protein localization to microtubule	1	1123.5×	0.003	ABHD17A
protein depalmitoylation	1	936.2×	0.003	ABHD17A
protein localization to nuclear envelope	1	702.2×	0.003	LMNB2
nuclear envelope organization	1	330.4×	0.005	LMNB2
negative regulation of NLRP3 inflammasome complex assembly	1	330.4×	0.005	ABHD17A
nuclear migration	1	244.2×	0.006	LMNB2
protein localization to membrane	1	200.6×	0.007	ABHD17A
regulation of postsynapse organization	1	175.5×	0.007	ABHD17A
heterochromatin formation	1	85.1×	0.013	LMNB2
signal transduction	1	5.3×	0.176	DIRAS1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LMNB2	0	0
DIRAS1	0	0
ABHD17A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
LMNB2	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	3	LMNB2, DIRAS1, ABHD17A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LMNB2	2	—
DIRAS1	0	—
ABHD17A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.