congenital nephrotic syndrome, Finnish type

Summary

congenital nephrotic syndrome, Finnish type (MONDO:0009732) is a disease caused by NPHS1 (GenCC Definitive), with 12 cohort genes and 1 clinical trial. The dominant Reactome pathway is Nephrin family interactions (3 cohort genes).

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: NPHS1 (GenCC Definitive)
• Cohort genes: 12
• ClinVar variants: 887
• Phenotypes (HPO): 5
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-5 / 10 000	12.2	Finland	Validated

Signs & symptoms

Clinical features (HPO)

5 HPO clinical features (Orphanet curated; top 5 by frequency):

HPO ID	Term	Frequency
HP:0000091	Abnormal renal tubule morphology	Very frequent (80-99%)
HP:0000093	Proteinuria	Very frequent (80-99%)
HP:0000100	Nephrotic syndrome	Very frequent (80-99%)
HP:0000696	Delayed eruption of permanent teeth	Very frequent (80-99%)
HP:0004639	Elevated amniotic fluid alpha-fetoprotein	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital nephrotic syndrome, Finnish type
Mondo ID	MONDO:0009732
OMIM	256300
Orphanet	839
DOID	DOID:0080390
NCIT	C122795
SNOMED CT	197601003
UMLS	C0403399
MedGen	98011
GARD	0001500
MedDRA	10060740
Is cancer (heuristic)	no

Also known as: CnF · congenital nephrotic syndrome - Finnish type · congenital nephrotic syndrome 1 · congenital nephrotic syndrome Finnish type · congenital nephrotic syndrome, Finnish type · Finnish congenital nephrosis · nephrosis 1, congenital, Finnish type · nephrosis, congenital · nephrotic syndrome - NPHS1 associated · nephrotic syndrome, type 1 · NPHS1

Data availability: 887 ClinVar variants · 5 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › nephrotic syndrome › familial nephrotic syndrome › congenital nephrotic syndrome, Finnish type

Related subtypes (17): nephrotic syndrome, type 4, LAMB2-related infantile-onset nephrotic syndrome, immunoglobulin-mediated membranoproliferative glomerulonephritis, familial idiopathic steroid-resistant nephrotic syndrome, nephrotic syndrome, type 20, nephrotic syndrome, type 22, nephrotic syndrome, type 23, nephrotic syndrome, type 24, nephrotic syndrome, IIa 26, nephrotic syndrome, type 17, nephrotic syndrome, type 18, nephrotic syndrome, type 19, nephrotic syndrome, type 21, nephrotic syndrome 14, nephrotic syndrome 15, nephrotic syndrome 16, idiopathic multidrug-resistant nephrotic syndrome

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

600 retrieved; paginated sample, class counts are floors:

223 uncertain significance, 146 likely pathogenic, 72 conflicting classifications of pathogenicity, 49 pathogenic/likely pathogenic, 47 likely benign, 36 pathogenic, 17 benign, 9 benign/likely benign, 1 conflicting classifications of pathogenicity; association; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
2582747	NM_004646.4(NPHS1):c.[2552C>T;2618_2620delinsCC]		Pathogenic	no assertion criteria provided
4724	NM_019109.5(ALG1):c.773C>T (p.Ser258Leu)	ALG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1378967	NM_004646.4(NPHS1):c.105G>A (p.Trp35Ter)	KIRREL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1950836	NM_004646.4(NPHS1):c.2T>C (p.Met1Thr)	KIRREL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2637930	NM_004646.4(NPHS1):c.67del (p.Gln23fs)	KIRREL2	Pathogenic	criteria provided, single submitter
2760285	NM_004646.4(NPHS1):c.163_164insA (p.Val55fs)	KIRREL2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065992	NM_004646.4(NPHS1):c.2728T>C (p.Ser910Pro)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072278	NM_004646.4(NPHS1):c.2387del (p.Gly796fs)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072444	NM_004646.4(NPHS1):c.671dup (p.Glu225fs)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073228	NM_004646.4(NPHS1):c.2686C>T (p.Gln896Ter)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073364	NM_004646.4(NPHS1):c.1117C>T (p.Arg373Ter)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074718	NM_004646.4(NPHS1):c.3213del (p.Leu1072fs)	NPHS1	Pathogenic	criteria provided, multiple submitters, no conflicts
1301890	NM_004646.4(NPHS1):c.621del (p.Ser208fs)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324818	NM_004646.4(NPHS1):c.1434G>A (p.Trp478Ter)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1339205	NM_004646.4(NPHS1):c.2600G>A (p.Gly867Asp)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1389608	NM_004646.4(NPHS1):c.44_45dup (p.Leu16fs)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1413819	NM_004646.4(NPHS1):c.2989_2990dup (p.Phe998fs)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1438822	NM_004646.4(NPHS1):c.816del (p.Pro272_Leu273insTer)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451777	NM_004646.4(NPHS1):c.2090_2094del (p.Arg697fs)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457104	NM_004646.4(NPHS1):c.450G>A (p.Trp150Ter)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1459549	NM_004646.4(NPHS1):c.795C>A (p.Cys265Ter)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1526163	NM_004646.4(NPHS1):c.869del (p.Gly290fs)	NPHS1	Pathogenic	criteria provided, single submitter
1722406	NM_004646.4(NPHS1):c.2587T>C (p.Cys863Arg)	NPHS1	Pathogenic	criteria provided, single submitter
1726021	NM_004646.4(NPHS1):c.295G>T (p.Glu99Ter)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
180463	NM_004646.4(NPHS1):c.1756A>G (p.Arg586Gly)	NPHS1	Pathogenic	no assertion criteria provided
1805064	NM_004646.4(NPHS1):c.542_543del (p.Ile180_Ser181insTer)	NPHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1809716	NM_004646.4(NPHS1):c.1745_1749del (p.Lys582fs)	NPHS1	Pathogenic	criteria provided, multiple submitters, no conflicts
188734	NM_004646.4(NPHS1):c.2335-1G>A	NPHS1	Pathogenic	criteria provided, multiple submitters, no conflicts
188761	NM_004646.4(NPHS1):c.2928G>T (p.Arg976Ser)	NPHS1	Pathogenic	criteria provided, multiple submitters, no conflicts
188816	NM_004646.4(NPHS1):c.565G>T (p.Glu189Ter)	NPHS1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 22 · 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
NPHS1	Definitive	Autosomal recessive	congenital nephrotic syndrome, Finnish type	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NPHS1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
NPHS1	Orphanet:839	Congenital nephrotic syndrome, Finnish type
SPINK1	Orphanet:103918	Tropical pancreatitis
SPINK1	Orphanet:700124	Autosomal recessive hereditary chronic pancreatitis
WT1	Orphanet:220	Denys-Drash syndrome
WT1	Orphanet:242	46,XY complete gonadal dysgenesis
WT1	Orphanet:251510	46,XY partial gonadal dysgenesis
WT1	Orphanet:3097	Meacham syndrome
WT1	Orphanet:347	Frasier syndrome
WT1	Orphanet:654	Nephroblastoma
WT1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
WT1	Orphanet:83469	Desmoplastic small round cell tumor
WT1	Orphanet:893	WAGR syndrome
NPHS2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
PLCE1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
ALG1	Orphanet:79327	ALG1-CDG
TTC21B	Orphanet:474	Jeune syndrome
TTC21B	Orphanet:93591	Infantile nephronophthisis
ABCC6	Orphanet:51608	Generalized arterial calcification of infancy
ABCC6	Orphanet:758	Pseudoxanthoma elasticum
ARHGDIA	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
PROS1	Orphanet:743	Severe hereditary thrombophilia due to congenital protein S deficiency

Cohort genes → proteins

12 cohort genes, 12 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	12

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NPHS1	HGNC:7908	ENSG00000161270	O60500	Nephrin	gencc,clinvar
SPINK1	HGNC:11244	ENSG00000164266	P00995	Serine protease inhibitor Kazal-type 1	clinvar
WT1	HGNC:12796	ENSG00000184937	P19544	Wilms tumor protein	clinvar
NPHS2	HGNC:13394	ENSG00000116218	Q9NP85	Podocin	clinvar
PLCE1	HGNC:17175	ENSG00000138193	Q9P212	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1	clinvar
PRODH2	HGNC:17325	ENSG00000250799	Q9UF12	Hydroxyproline dehydrogenase	clinvar
ALG1	HGNC:18294	ENSG00000033011	Q9BT22	Chitobiosyldiphosphodolichol beta-mannosyltransferase	clinvar
KIRREL2	HGNC:18816	ENSG00000126259	Q6UWL6	Kin of IRRE-like protein 2	clinvar
TTC21B	HGNC:25660	ENSG00000123607	Q7Z4L5	Tetratricopeptide repeat protein 21B	clinvar
ABCC6	HGNC:57	ENSG00000091262	O95255	ATP-binding cassette sub-family C member 6	clinvar
ARHGDIA	HGNC:678	ENSG00000141522	P52565	Rho GDP-dissociation inhibitor 1	clinvar
PROS1	HGNC:9456	ENSG00000184500	P07225	Vitamin K-dependent protein S	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NPHS1	Nephrin	Seems to play a role in the development or function of the kidney glomerular filtration barrier.
SPINK1	Serine protease inhibitor Kazal-type 1	Serine protease inhibitor which exhibits anti-trypsin activity.
WT1	Wilms tumor protein	Transcription factor that plays an important role in cellular development and cell survival.
NPHS2	Podocin	Plays a role in the regulation of glomerular permeability, acting probably as a linker between the plasma membrane and the cytoskeleton.
PLCE1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1	The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.
PRODH2	Hydroxyproline dehydrogenase	Dehydrogenase that converts trans-4-L-hydroxyproline to delta-1-pyrroline-3-hydroxy-5-carboxylate (Hyp) using ubiquinone-10 as the terminal electron acceptor.
ALG1	Chitobiosyldiphosphodolichol beta-mannosyltransferase	Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation.
KIRREL2	Kin of IRRE-like protein 2	May regulate basal insulin secretion.
TTC21B	Tetratricopeptide repeat protein 21B	Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs).
ABCC6	ATP-binding cassette sub-family C member 6	ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells.
ARHGDIA	Rho GDP-dissociation inhibitor 1	Controls Rho proteins homeostasis.
PROS1	Vitamin K-dependent protein S	Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa.

Protein-family classification

Druggable: 6 · Difficult: 1 · Unknown: 5 · 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
Antibody/Immunoglobulin	2	4.9×	0.180
Enzyme (other)	3	3.0×	0.180
Transporter	1	6.5×	0.240
Other/Unknown	5	0.8×	0.899
Transcription factor	1	0.7×	0.899

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NPHS1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
SPINK1	Other/Unknown	no		Prot_inh_Kazal-m, Kazal_dom, Kazal_dom_sf
WT1	Transcription factor	no		Wilms_tumour_N, Znf_C2H2_type, Znf_C2H2_sf
NPHS2	Other/Unknown	no		Band_7, Stomatin_HflK_fam, Band_7/stomatin-like_CS
PLCE1	Enzyme (other)	yes	3.1.4.11	C2_dom, RA_dom, PLipase_C_PInositol-sp_X_dom
PRODH2	Enzyme (other)	yes	1.5.5.3	Proline_DH_dom, Proline_oxidase, FAD-linked_oxidoreductase-like
ALG1	Enzyme (other)	yes	2.4.1.142	Glyco_trans_1, ALG1-like
KIRREL2	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
TTC21B	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC21A/TTC21B
ABCC6	Transporter	yes	7.6.2.3	ABC_transporter-like_ATP-bd, AAA+_ATPase, MRP
ARHGDIA	Other/Unknown	no		Rho_GDI, Ig_E-set, RhoGDI_dom_sf
PROS1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, GLA_domain, EGF

Expression context

Cohort genes with no expression data: 0.

12 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)	12
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	4
metanephric glomerulus	3
renal glomerulus	3
buccal mucosa cell	2
liver	2
right lobe of liver	2
vena cava	1
epithelial cell of pancreas	1
islet of Langerhans	1
germinal epithelium of ovary	1
kidney epithelium	1
ventricular zone	1
adult mammalian kidney	1
stromal cell of endometrium	1
left ventricle myocardium	1
pancreas	1
calcaneal tendon	1
cerebellar hemisphere	1
right uterine tube	1
duodenum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NPHS1	147	tissue_specific	marker	buccal mucosa cell, body of pancreas, vena cava
SPINK1	192	broad	marker	body of pancreas, islet of Langerhans, epithelial cell of pancreas
WT1	168	broad	marker	germinal epithelium of ovary, renal glomerulus, metanephric glomerulus
NPHS2	47	tissue_specific	marker	renal glomerulus, metanephric glomerulus, kidney epithelium
PLCE1	271	broad	marker	renal glomerulus, metanephric glomerulus, ventricular zone
PRODH2	102	tissue_specific	marker	right lobe of liver, liver, adult mammalian kidney
ALG1	185	ubiquitous	marker	stromal cell of endometrium, buccal mucosa cell, body of pancreas
KIRREL2	97	tissue_specific	marker	body of pancreas, pancreas, left ventricle myocardium
TTC21B	179	ubiquitous	marker	right uterine tube, calcaneal tendon, cerebellar hemisphere
ABCC6	136		marker	right lobe of liver, liver, duodenum
ARHGDIA	292	ubiquitous	marker	granulocyte, colonic epithelium, mucosa of transverse colon
PROS1	276	ubiquitous	marker	choroid plexus epithelium, bronchial epithelial cell, synovial joint

Protein interactions among cohort

Intra-cohort edges: 8.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WT1	3,938
ARHGDIA	2,778
ALG1	2,187
NPHS2	1,811
PRODH2	1,715
NPHS1	1,690
TTC21B	1,588
PLCE1	1,560
PROS1	1,129
KIRREL2	1,077

Intra-cohort edges

A	B	Sources
KIRREL2	NPHS1	string_interaction
KIRREL2	NPHS2	string_interaction
NPHS1	NPHS2	biogrid_interaction, string_interaction
NPHS1	PLCE1	string_interaction
NPHS1	WT1	string_interaction
NPHS2	PLCE1	string_interaction
NPHS2	WT1	string_interaction
PLCE1	WT1	string_interaction

Structural data

PDB: 8 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WT1	P19544	28
ARHGDIA	P52565	21
SPINK1	P00995	5
ABCC6	O95255	4
PLCE1	Q9P212	3
TTC21B	Q7Z4L5	3
PROS1	P07225	3
NPHS1	O60500	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ALG1	Q9BT22	93.24
PRODH2	Q9UF12	87.87
KIRREL2	Q6UWL6	75.30
NPHS2	Q9NP85	75.00

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 48. Enrichment computed across 12 evidence-associated genes (12 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 12 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Nephrin family interactions	3	119.0×	9e-05	NPHS1, NPHS2, KIRREL2
Defective ALG1 causes CDG-1k	1	951.7×	0.017	ALG1
Defective ABCC6 causes PXE	1	951.7×	0.017	ABCC6
Proline catabolism	1	317.2×	0.025	PRODH2
Defective cleavage of FV variant at a.a.534	1	317.2×	0.025	PROS1
Defective cleavage of FV variant at R334	1	317.2×	0.025	PROS1
Axonal growth stimulation	1	237.9×	0.029	ARHGDIA
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus	1	105.7×	0.046	PROS1
Axonal growth inhibition (RHOA activation)	1	105.7×	0.046	ARHGDIA
Gamma-carboxylation of protein precursors	1	95.2×	0.046	PROS1
Removal of aminoterminal propeptides from gamma-carboxylated proteins	1	95.2×	0.046	PROS1
Nephron development	1	73.2×	0.054	WT1
Glyoxylate metabolism and glycine degradation	1	63.4×	0.056	PRODH2
Transcriptional regulation of testis differentiation	1	59.5×	0.056	WT1
Diseases associated with N-glycosylation of proteins	1	52.9×	0.056	ALG1
Amplification and propagation of coagulation cascade	1	52.9×	0.056	PROS1
Initiation of coagulation cascade	1	39.6×	0.070	PROS1
ABC transporter disorders	1	36.6×	0.071	ABCC6
Synthesis of IP3 and IP4 in the cytosol	1	35.2×	0.071	PLCE1
RHOH GTPase cycle	1	25.7×	0.090	ARHGDIA
Developmental Lineage of Pancreatic Acinar Cells	1	25.0×	0.090	SPINK1
Dengue Virus Attachment and Entry	1	21.6×	0.099	PROS1
Regulation of clotting cascade	1	19.4×	0.100	PROS1
Regulation of Complement cascade	1	19.4×	0.100	PROS1
Developmental Cell Lineages	1	18.7×	0.100	SPINK1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	17.3×	0.104	ALG1
Intraflagellar transport	1	16.7×	0.104	TTC21B
Hedgehog ‘off’ state	1	14.9×	0.112	TTC21B
RHOG GTPase cycle	1	12.4×	0.126	ARHGDIA
RHOC GTPase cycle	1	12.2×	0.126	ARHGDIA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 12 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glomerular basement membrane development	2	255.3×	0.002	NPHS1, WT1
glomerulus development	2	216.1×	0.002	WT1, PLCE1
negative regulation of metanephric glomerular mesangial cell proliferation	1	1404.3×	0.012	WT1
regulation of animal organ formation	1	702.2×	0.012	WT1
obsolete negative regulation of nitric oxide mediated signal transduction	1	702.2×	0.012	SPINK1
inorganic diphosphate transport	1	702.2×	0.012	ABCC6
adrenal cortex formation	1	702.2×	0.012	WT1
slit diaphragm assembly	1	702.2×	0.012	NPHS1
visceral serous pericardium development	1	702.2×	0.012	WT1
posterior mesonephric tubule development	1	702.2×	0.012	WT1
metanephric podocyte development	1	702.2×	0.012	NPHS2
regulation of intraciliary retrograde transport	1	702.2×	0.012	TTC21B
positive regulation of metanephric ureteric bud development	1	702.2×	0.012	WT1
gene expression	3	20.0×	0.012	NPHS1, NPHS2, ABCC6
obsolete L-proline catabolic process to L-glutamate	1	468.1×	0.016	PRODH2
L-proline catabolic process	1	351.1×	0.016	PRODH2
positive regulation of heart growth	1	351.1×	0.016	WT1
metanephric S-shaped body morphogenesis	1	351.1×	0.016	WT1
protein localization to non-motile cilium	1	351.1×	0.016	TTC21B
inhibition of non-skeletal tissue mineralization	1	351.1×	0.016	ABCC6
negative regulation of female gonad development	1	351.1×	0.016	WT1
thorax and anterior abdomen determination	1	280.9×	0.017	WT1
regulation of acrosome reaction	1	280.9×	0.017	SPINK1
cardiac muscle cell fate commitment	1	280.9×	0.017	WT1
metanephric epithelium development	1	280.9×	0.017	WT1
cellular response to gonadotropin stimulus	1	234.1×	0.019	WT1
negative regulation of eating behavior	1	234.1×	0.019	TTC21B
leukotriene transport	1	200.6×	0.020	ABCC6
metanephric mesenchyme development	1	200.6×	0.020	WT1
negative regulation of calcium ion import	1	200.6×	0.020	SPINK1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 12

Druggability breadth: 6 of 12 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
NPHS1	0	0
SPINK1	0	0
WT1	0	0
NPHS2	0	0
PLCE1	0	0
PRODH2	0	0
ALG1	0	0
KIRREL2	0	0
TTC21B	0	0
ABCC6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
ABCC6	10	Functional:9, Binding:1
PRODH2	3	Binding:3
ARHGDIA	2	Binding:2
ALG1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PLCE1	3.1.4.11	phosphoinositide phospholipase C
PRODH2	1.5.5.3	hydroxyproline dehydrogenase
ALG1	2.4.1.142	chitobiosyldiphosphodolichol beta-mannosyltransferase
ABCC6	7.6.2.3	ABC-type glutathione-S-conjugate transporter

Pharmacogenomics

Cohort genes with a PharmGKB record: 12; 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	3	NPHS1, PLCE1, ABCC6
D	Druggable family + AlphaFold only, no drug	3	PRODH2, ALG1, KIRREL2
E	Difficult family or no structure, no drug	6	SPINK1, WT1, NPHS2, TTC21B, ARHGDIA, PROS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NPHS1	0	—
SPINK1	0	—
WT1	0	—
NPHS2	0	—
PLCE1	0	—
PRODH2	3	—
ALG1	1	—
KIRREL2	0	—
TTC21B	0	—
ABCC6	10	—
ARHGDIA	2	—
PROS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening