Pulmonary hypertension, neonatal, susceptibility to

Summary

Pulmonary hypertension, neonatal, susceptibility to (MONDO:0014151) is a disease with 2 cohort genes and 1 clinical trial. Top therapeutic interventions include gabapentin.

At a glance

• Cohort genes: 2
• ClinVar variants: 173
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pulmonary hypertension, neonatal, susceptibility to
Mondo ID	MONDO:0014151
OMIM	615371
UMLS	C3714958
MedGen	811528
Is cancer (heuristic)	no

Also known as: PHN · pulmonary hypertension, neonatal, susceptibility to

Data availability: 173 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › pulmonary hypertension, neonatal, 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, 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, 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

173 retrieved; paginated sample, class counts are floors:

71 likely pathogenic, 49 pathogenic/likely pathogenic, 22 conflicting classifications of pathogenicity, 16 pathogenic, 8 uncertain significance, 6 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066946	NM_001875.5(CPS1):c.3607T>C (p.Ser1203Pro)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069202	NM_001875.5(CPS1):c.1432C>T (p.Gln478Ter)	CPS1	Pathogenic	criteria provided, multiple submitters, no conflicts
1069203	NM_001875.5(CPS1):c.1549+1G>T	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069282	NM_001875.5(CPS1):c.4191G>A (p.Trp1397Ter)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070204	NM_001875.5(CPS1):c.1424del (p.Gly475fs)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076647	NM_001875.5(CPS1):c.3520C>T (p.Arg1174Ter)	CPS1	Pathogenic	criteria provided, multiple submitters, no conflicts
1192241	NM_001875.5(CPS1):c.2798del (p.Arg932_Leu933insTer)	CPS1	Pathogenic	criteria provided, multiple submitters, no conflicts
1343551	NM_001875.5(CPS1):c.3337-1G>T	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1361235	NM_001875.5(CPS1):c.420C>A (p.Tyr140Ter)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1400087	NM_001875.5(CPS1):c.3380T>A (p.Leu1127Ter)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1450174	NM_001875.5(CPS1):c.2819G>A (p.Trp940Ter)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457814	NM_001875.5(CPS1):c.3682del (p.Arg1228fs)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458373	NM_001875.5(CPS1):c.1370T>G (p.Val457Gly)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1968039	NM_001875.5(CPS1):c.1596del (p.Val533fs)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2036112	NM_001875.5(CPS1):c.2525del (p.Glu842fs)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2077457	NM_001875.5(CPS1):c.869dup (p.Leu290fs)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2203247	NM_001875.5(CPS1):c.866del (p.Pro289fs)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2203249	NM_001875.5(CPS1):c.2548C>T (p.Arg850Cys)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2419	NM_001875.5(CPS1):c.1631C>T (p.Thr544Met)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2420	NM_001875.5(CPS1):c.130C>T (p.Gln44Ter)	CPS1	Pathogenic	criteria provided, single submitter
2426	NM_001875.5(CPS1):c.2359C>T (p.Arg787Ter)	CPS1	Pathogenic	criteria provided, multiple submitters, no conflicts
2680878	NM_001875.5(CPS1):c.1812_1813del (p.Glu604fs)	CPS1	Pathogenic	criteria provided, single submitter
2680888	NM_001875.5(CPS1):c.3336+2T>A	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680898	NM_001875.5(CPS1):c.3404+1G>A	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680902	NM_001875.5(CPS1):c.1123C>T (p.Gln375Ter)	CPS1	Pathogenic	criteria provided, single submitter
2680904	NM_001875.5(CPS1):c.3276_3288del (p.Phe1092fs)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680907	NM_001875.5(CPS1):c.1941_1944del (p.Cys648fs)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680908	NM_001875.5(CPS1):c.3136C>T (p.Gln1046Ter)	CPS1	Pathogenic	criteria provided, multiple submitters, no conflicts
2680913	NM_001875.5(CPS1):c.1390_1397del (p.Pro464fs)	CPS1	Pathogenic	criteria provided, single submitter
2734366	NM_001875.5(CPS1):c.1759C>T (p.Arg587Cys)	CPS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CPS1	Orphanet:147	Carbamoyl-phosphate synthetase 1 deficiency

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
CPS1	HGNC:2323	ENSG00000021826	P31327	Carbamoyl-phosphate synthase [ammonia], mitochondrial	clinvar
PM20D1	HGNC:26518	ENSG00000162877	Q6GTS8	N-fatty-acyl-amino acid synthase/hydrolase PM20D1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CPS1	Carbamoyl-phosphate synthase [ammonia], mitochondrial	Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell.
PM20D1	N-fatty-acyl-amino acid synthase/hydrolase PM20D1	Secreted enzyme that regulates the endogenous N-fatty acyl amino acid (NAAs) tissue and circulating levels by functioning as a bidirectional NAA synthase/hydrolase.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	18.3×	0.108
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CPS1	Enzyme (other)	yes	6.3.4.16	CarbamoylP_synth_ssu_N, CPAse_ATP-bd, CPSase_lsu_oligo
PM20D1	Protease	yes		Peptidase_M20, Peptidase_M20_dimer, Bact_exopeptidase_dim_dom

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
jejunal mucosa	1
liver	1
right lobe of liver	1
mammalian vulva	1
upper arm skin	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CPS1	209	ubiquitous	marker	liver, right lobe of liver, jejunal mucosa
PM20D1	144	tissue_specific	marker	upper leg skin, upper arm skin, mammalian vulva

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CPS1	2,830
PM20D1	1,692

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CPS1	P31327	14

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PM20D1	Q6GTS8	89.55

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
CPS1 variants cause CPS1 deficiency	1	5710.0×	5e-04	CPS1
Oleoyl-phe metabolism	1	2855.0×	5e-04	PM20D1
Urea cycle	1	439.2×	0.002	CPS1

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
carbamoyl phosphate biosynthetic process	1	8426.0×	0.003	CPS1
obsolete amide biosynthetic process	1	4213.0×	0.003	PM20D1
monoatomic anion homeostasis	1	4213.0×	0.003	CPS1
cellular response to oleic acid	1	2808.7×	0.003	CPS1
L-citrulline biosynthetic process	1	2106.5×	0.003	CPS1
cellular response to ammonium ion	1	1685.2×	0.003	CPS1
‘de novo’ pyrimidine nucleobase biosynthetic process	1	1404.3×	0.003	CPS1
midgut development	1	1053.2×	0.003	CPS1
obsolete amide catabolic process	1	1053.2×	0.003	PM20D1
response to amine	1	936.2×	0.003	CPS1
homocysteine metabolic process	1	936.2×	0.003	CPS1
response to alcohol	1	766.0×	0.004	CPS1
nitric oxide metabolic process	1	702.2×	0.004	CPS1
urea cycle	1	648.1×	0.004	CPS1
L-glutamine metabolic process	1	648.1×	0.004	CPS1
hepatocyte differentiation	1	601.9×	0.004	CPS1
response to dexamethasone	1	601.9×	0.004	CPS1
response to growth hormone	1	561.7×	0.004	CPS1
adaptive thermogenesis	1	526.6×	0.004	PM20D1
response to amino acid	1	495.6×	0.004	CPS1
cellular response to glucagon stimulus	1	421.3×	0.004	CPS1
amino acid metabolic process	1	401.2×	0.004	PM20D1
triglyceride catabolic process	1	401.2×	0.004	CPS1
response to zinc ion	1	312.1×	0.005	CPS1
cellular response to fibroblast growth factor stimulus	1	271.8×	0.005	CPS1
response to food	1	247.8×	0.006	CPS1
response to starvation	1	234.1×	0.006	CPS1
vasodilation	1	183.2×	0.007	CPS1
cellular response to cAMP	1	145.3×	0.009	CPS1
energy homeostasis	1	135.9×	0.009	PM20D1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CPS1	0	0
PM20D1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CPS1	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CPS1	6.3.4.16	carbamoyl-phosphate synthase (ammonia)

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

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	1	CPS1
D	Druggable family + AlphaFold only, no drug	1	PM20D1
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CPS1	3	—
PM20D1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00475904	PHASE2	COMPLETED	A Comparison of EpiCept™ NP-1 Topical Cream vs. Oral Gabapentin in Postherpetic Neuralgia (PHN)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GABAPENTIN	4	1