Diabetic kidney disease

disease

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Also known as diabetic nephropathyDKDtype 1 diabetes nephropathytype 2 diabetes nephropathy

Summary

Diabetic kidney disease (MONDO:0005016) is a disease with 59 cohort genes (214 GWAS associations across 51 studies) and 446 clinical trials. Top therapeutic interventions include lisinopril anhydrous, losartan, and canagliflozin anhydrous.

At a glance

Cohort genes: 59
GWAS associations: 214
Clinical trials: 446

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	diabetic kidney disease
Mondo ID	MONDO:0005016
EFO	EFO:0000401
MeSH	D003928
ICD-11	615062102
NCIT	C84417
SNOMED CT	127013003
UMLS	C0011881
MedGen	8352
Is cancer (heuristic)	no

Also known as: diabetic nephropathy · DKD · type 1 diabetes nephropathy · type 2 diabetes nephropathy

Data availability: 214 GWAS associations (51 studies) · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › diabetic kidney disease

Genetics & variants

GWAS landscape

214 GWAS associations across 51 studies. Top hits map to 22 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2237896	2e-32	KCNQ1	?
rs3128852	8e-25	OR12D2, OR5V1	?
chr21:32804223	8e-22		C	9.41
chr21:32799557	2e-19		C	9.54
chr5:29705905	1e-16		C	6.81
chr10:114758349	2e-16		T	1.4
chr20:10760829	2e-15		C	7.97
chr8:74004192	4e-15		A	6.39
chr8:49547701	1e-12		C	5.38
chr17:77708184	3e-12		A	4.3
chr8:74005904	3e-12		T	4.97
rs55703767	5e-12	COL4A3, MFF-DT	G	1.27
chr6:12618492	3e-11		G	2.22
chr22:36656555	9e-11		G	1.3
chr6:42474989	1e-10		T	3
chr2:46485186	2e-10		C	3.92
chr22:36618953	2e-10		C	1.36
chr3:165051826	4e-10		T	1.62
chr2:151713161	7e-10		A	1.58
rs56094641	8e-10	FTO	?	1.21
rs117744700	8e-10	MFSD14B	?
chr10:13527266	1e-09		G	1.45
chr6:12617159	1e-09		C	2.28
rs12917707	1e-09	UMOD	?	0.8
rs12437854	2e-09	SEPHS1P2 - LINC01579	G	1.8
chr17:7289638	2e-09		A	3.86
rs75029938	2e-09	GRAMD2B	T	1.89
rs425827	3e-09	KRT6B	A	5.31
rs141560952	4e-09	DIS3L2, NRBF2P6	AGGG	192.63
rs12523822	6e-09	RPL31P29 - SCAF8	?	1.75

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90244673	Khattab A	2022	8,486	10,354	Nidogen-1 could play a role in diabetic kidney disease development in type 2 diabetes: a genome-wide association meta-analysis.
GCST009292	Salem RM	2019	7,247	12,053	Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen.
GCST005881	van Zuydam NR	2018	5,908	4,967	A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes.
GCST90244670	Khattab A	2022	5,141	7,982	Nidogen-1 could play a role in diabetic kidney disease development in type 2 diabetes: a genome-wide association meta-analysis.
GCST009278	Salem RM	2019	4,948	12,076	Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen.
GCST009286	Salem RM	2019	4,266	14,838	Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen.
GCST007949	Guan M	2019	3,432	6,977	Genome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans.
GCST005895	van Zuydam NR	2018	3,345	2,372	A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes.
GCST005888	van Zuydam NR	2018	3,096	4,967	A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes.
GCST009289	Salem RM	2019	2,987	11,766	Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	2
Tier 3: regulatory	0
Tier 4: intronic/intergenic	46

MAF distribution

Bucket	Variants
common (>=0.05)	24
low_freq (0.01-0.05)	23
rare (<0.01)	3
unknown	0

Functional consequences

Consequence	Count
unknown	26
intron_variant	12
intergenic_variant	7
missense_variant	1
5_prime_UTR_variant	1
splice_region_variant	1
inframe_insertion	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2237896	11	2837210	G>A,T	0.05	intron_variant	KCNQ1	2e-32	Tier 4: intronic/intergenic
rs3128852	6	29396358	T>A,C	0.05	intron_variant	OR12D2, OR5V1	8e-25	Tier 4: intronic/intergenic
chr21:32804223				0.01			8e-22	Tier 4: intronic/intergenic
chr21:32799557				0.01			2e-19	Tier 4: intronic/intergenic
chr5:29705905				0.01			1e-16	Tier 4: intronic/intergenic
chr10:114758349				0.3			2e-16	Tier 4: intronic/intergenic
chr20:10760829				0.01			2e-15	Tier 4: intronic/intergenic
chr8:74004192				0.01			4e-15	Tier 4: intronic/intergenic
chr8:49547701				0.01			1e-12	Tier 4: intronic/intergenic
chr17:77708184				0.01			3e-12	Tier 4: intronic/intergenic
chr8:74005904				0.01			3e-12	Tier 4: intronic/intergenic
rs55703767	2	227256385	G>A,T	0.206	missense_variant	COL4A3, MFF-DT	5e-12	Tier 1: coding
chr6:12618492				0.03			3e-11	Tier 4: intronic/intergenic
chr22:36656555				0.45			9e-11	Tier 4: intronic/intergenic
chr6:42474989				0.01			1e-10	Tier 4: intronic/intergenic
chr2:46485186				0.01			2e-10	Tier 4: intronic/intergenic
chr22:36618953				0.26			2e-10	Tier 4: intronic/intergenic
chr3:165051826				0.06			4e-10	Tier 4: intronic/intergenic
chr2:151713161				0.08			7e-10	Tier 4: intronic/intergenic
rs56094641	16	53772541	A>G,T	0.05	intron_variant	FTO	8e-10	Tier 4: intronic/intergenic
rs117744700	9	94387628	G>C,T	0.05	intron_variant	MFSD14B	8e-10	Tier 4: intronic/intergenic
chr10:13527266				0.11			1e-09	Tier 4: intronic/intergenic
chr6:12617159				0.02			1e-09	Tier 4: intronic/intergenic
rs12917707	16	20356368	G>A,T	0.05	5_prime_UTR_variant	UMOD	1e-09	Tier 2: splice/UTR
rs12437854	15	93598604	T>G	0.04	intergenic_variant	SEPHS1P2 - LINC01579	2e-09	Tier 4: intronic/intergenic
chr17:7289638				0.01			2e-09	Tier 4: intronic/intergenic
rs75029938	5	126437641	C>T	0.042	intron_variant	GRAMD2B	2e-09	Tier 4: intronic/intergenic
rs425827	12	52449750	T>A,C	0.02	splice_region_variant	KRT6B	3e-09	Tier 2: splice/UTR
rs141560952	2	232343414	A>AGGG	0.001	inframe_insertion	DIS3L2, NRBF2P6	4e-09	Tier 1: coding
rs12523822	6	154633286	C>G,T	0.26	intergenic_variant	RPL31P29 - SCAF8	6e-09	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 41 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SOX11	Orphanet:1465	Coffin-Siris syndrome
XRCC2	Orphanet:227535	Hereditary breast cancer
XRCC2	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
XRCC2	Orphanet:84	Fanconi anemia
CNTNAP2	Orphanet:163681	CNTNAP2-related developmental and epileptic encephalopathy
COLEC11	Orphanet:293843	3MC syndrome
CHAT	Orphanet:98914	Presynaptic congenital myasthenic syndromes
SASH1	Orphanet:231040	Familial generalized lentiginosis
SASH1	Orphanet:447961	Pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome
COL4A3	Orphanet:653722	Digenic Alport syndrome
COL4A3	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
COL4A3	Orphanet:88918	Autosomal dominant Alport syndrome
COL4A3	Orphanet:88919	Autosomal recessive Alport syndrome
MED13L	Orphanet:216718	Isolated congenitally uncorrected transposition of the great arteries
MED13L	Orphanet:369891	Developmental delay-facial dysmorphism syndrome due to MED13L deficiency
FTO	Orphanet:210144	Lethal polymalformative syndrome, Boissel type
MCTP2	Orphanet:1596	Distal deletion 15q syndrome
TTC21B	Orphanet:474	Jeune syndrome
TTC21B	Orphanet:93591	Infantile nephronophthisis
MSRB3	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
PRCD	Orphanet:791	Retinitis pigmentosa
ERBB4	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
ERBB4	Orphanet:803	Amyotrophic lateral sclerosis
GUCY1A1	Orphanet:401945	Moyamoya disease with early-onset achalasia
HMGA2	Orphanet:276148	Benign epithelial tumor of salivary glands
HMGA2	Orphanet:397590	Silver-Russell syndrome due to a point mutation
HMGA2	Orphanet:94063	12q14 microdeletion syndrome
HMGA2	Orphanet:99970	Dedifferentiated liposarcoma
HMGA2	Orphanet:99971	Well-differentiated liposarcoma
ANXA11	Orphanet:803	Amyotrophic lateral sclerosis
ITGA6	Orphanet:79403	Junctional epidermolysis bullosa with pyloric atresia
APOL1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
ITPR1	Orphanet:1065	Aniridia-cerebellar ataxia-intellectual disability syndrome
ITPR1	Orphanet:208513	Spinocerebellar ataxia type 29
ITPR1	Orphanet:98769	Spinocerebellar ataxia type 15/16
AFF3	Orphanet:632603	Mesomelic dysplasia-digital anomalies-intellectual disability syndrome
MAT1A	Orphanet:168598	Methionine adenosyltransferase I/III deficiency
MYH9	Orphanet:182050	MYH9-related syndromic thrombocytopenia
MYH9	Orphanet:477742	Nodular fasciitis
MYH9	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
AUH	Orphanet:67046	3-methylglutaconic aciduria type 1

Cohort genes → proteins

59 cohort genes, 57 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	59

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNF10	HGNC:10055	ENSG00000022840	Q8N5U6	E3 ubiquitin-protein ligase RNF10	gwas
RPS12	HGNC:10385	ENSG00000112306	P25398	Small ribosomal subunit protein eS12	gwas
SNCAIP	HGNC:11139	ENSG00000064692	Q9Y6H5	Synphilin-1	gwas
SOX11	HGNC:11191	ENSG00000176887	P35716	Transcription factor SOX-11	gwas
STAC	HGNC:11353	ENSG00000144681	Q99469	SH3 and cysteine-rich domain-containing protein	gwas
SUCLG2	HGNC:11450	ENSG00000172340	Q96I99	Succinate–CoA ligase [GDP-forming] subunit beta, mitochondrial	gwas
TNFRSF19	HGNC:11915	ENSG00000127863	Q9NS68	Tumor necrosis factor receptor superfamily member 19	gwas
XRCC2	HGNC:12829	ENSG00000196584	O43543	DNA repair protein XRCC2	gwas
CNTNAP2	HGNC:13830	ENSG00000174469	Q9UHC6	Contactin-associated protein-like 2	gwas
SORBS1	HGNC:14565	ENSG00000095637	Q9BX66	Sorbin and SH3 domain-containing protein 1	gwas
NAV3	HGNC:15998	ENSG00000067798	Q8IVL0	Neuron navigator 3	gwas
ELMO1	HGNC:16286	ENSG00000155849	Q92556	Engulfment and cell motility protein 1	gwas
SORCS3	HGNC:16699	ENSG00000156395	Q9UPU3	VPS10 domain-containing receptor SorCS3	gwas
COLEC11	HGNC:17213	ENSG00000118004	Q9BWP8	Collectin-11	gwas
ALLC	HGNC:17377	ENSG00000151360	Q8N6M5	Probable inactive allantoicase	gwas
KCNH7	HGNC:18863	ENSG00000184611	Q9NS40	Voltage-gated inwardly rectifying potassium channel KCNH7	gwas
CHAT	HGNC:1912	ENSG00000070748	P28329	Choline O-acetyltransferase	gwas
SASH1	HGNC:19182	ENSG00000111961	O94885	SAM and SH3 domain-containing protein 1	gwas
SCAF8	HGNC:20959	ENSG00000213079	Q9UPN6	SR-related and CTD-associated factor 8	gwas
COL4A3	HGNC:2204	ENSG00000169031	Q01955	Collagen alpha-3(IV) chain	gwas
MED13L	HGNC:22962	ENSG00000123066	Q71F56	Mediator of RNA polymerase II transcription subunit 13-like	gwas
CNKSR3	HGNC:23034	ENSG00000153721	Q6P9H4	Connector enhancer of kinase suppressor of ras 3	gwas
ABTB3	HGNC:23844	ENSG00000151136	A6QL63	Ankyrin repeat- and BTB/POZ domain-containing protein 3	gwas
FTO	HGNC:24678	ENSG00000140718	Q9C0B1	Alpha-ketoglutarate-dependent dioxygenase FTO	gwas
GRAMD2B	HGNC:24911	ENSG00000155324	Q96HH9	GRAM domain-containing protein 2B	gwas
KDM4D	HGNC:25498	ENSG00000186280	Q6B0I6	Lysine-specific demethylase 4D	gwas
MCTP2	HGNC:25636	ENSG00000140563	Q6DN12	Multiple C2 and transmembrane domain-containing protein 2	gwas
TTC21B	HGNC:25660	ENSG00000123607	Q7Z4L5	Tetratricopeptide repeat protein 21B	gwas
CGNL1	HGNC:25931	ENSG00000128849	Q0VF96	Cingulin-like protein 1	gwas
TTC39C	HGNC:26595	ENSG00000168234	Q8N584	Tetratricopeptide repeat protein 39C	gwas
IGSF22	HGNC:26750	ENSG00000179057	Q8N9C0	Immunoglobulin superfamily member 22	gwas
SMIM13	HGNC:27356	ENSG00000224531	P0DJ93	Small integral membrane protein 13	gwas
MSRB3	HGNC:27375	ENSG00000174099	Q8IXL7	Methionine-R-sulfoxide reductase B3	gwas
COQ5	HGNC:28722	ENSG00000110871	Q5HYK3	2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial	gwas
WWC1	HGNC:29435	ENSG00000113645	Q8IX03	Protein KIBRA	gwas
RGMA	HGNC:30308	ENSG00000182175	Q96B86	Repulsive guidance molecule A	gwas
TBC1D31	HGNC:30888	ENSG00000156787	Q96DN5	TBC1 domain family member 31	gwas
PRCD	HGNC:32528	ENSG00000214140	Q00LT1	Photoreceptor disk component PRCD	gwas
ERBB4	HGNC:3432	ENSG00000178568	Q15303	Receptor tyrosine-protein kinase erbB-4	gwas
GABRR1	HGNC:4090	ENSG00000146276	P24046	Gamma-aminobutyric acid receptor subunit rho-1	gwas
TRABD2B	HGNC:44200	ENSG00000269113	A6NFA1	Metalloprotease TIKI2	gwas
GUCY1A1	HGNC:4685	ENSG00000164116	Q02108	Guanylate cyclase soluble subunit alpha-1	gwas
PRNCR1	HGNC:48942	ENSG00000282961		prostate cancer associated non-coding RNA 1	gwas
HMGA2	HGNC:5009	ENSG00000149948	P52926	High mobility group protein HMGI-C	gwas
LINC01266	HGNC:50309	ENSG00000224957		long intergenic non-protein coding RNA 1266	gwas
ANXA11	HGNC:535	ENSG00000122359	P50995	Annexin A11	gwas
ITGA6	HGNC:6142	ENSG00000091409	P23229	Integrin alpha-6	gwas
APOL1	HGNC:618	ENSG00000100342	O14791	Apolipoprotein L1	gwas
ITPR1	HGNC:6180	ENSG00000150995	Q14643	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR1	gwas
AFF3	HGNC:6473	ENSG00000144218	P51826	AF4/FMR2 family member 3	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF10	E3 ubiquitin-protein ligase RNF10	E3 ubiquitin-protein ligase that catalyzes monoubiquitination of 40S ribosomal proteins RPS2/us5 and RPS3/us3 in response to ribosome stalling.
RPS12	Small ribosomal subunit protein eS12	Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit.
SNCAIP	Synphilin-1	Isoform 2 inhibits the ubiquitin ligase activity of SIAH1 and inhibits proteasomal degradation of target proteins.
SOX11	Transcription factor SOX-11	Transcription factor that acts as a transcriptional activator.
STAC	SH3 and cysteine-rich domain-containing protein	Promotes expression of the ion channel CACNA1H at the cell membrane, and thereby contributes to the regulation of channel activity.
SUCLG2	Succinate–CoA ligase [GDP-forming] subunit beta, mitochondrial	GTP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of GTP and thus represents the only step of substrate-level phosphorylation in the TCA.
TNFRSF19	Tumor necrosis factor receptor superfamily member 19	Can mediate activation of JNK and NF-kappa-B.
XRCC2	DNA repair protein XRCC2	Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions.
CNTNAP2	Contactin-associated protein-like 2	Required for gap junction formation.
SORBS1	Sorbin and SH3 domain-containing protein 1	Plays a role in tyrosine phosphorylation of CBL by linking CBL to the insulin receptor.
NAV3	Neuron navigator 3	Is involved in microtubule cytoskeleton organization and plays a role in cell migration.
ELMO1	Engulfment and cell motility protein 1	Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility.
SORCS3	VPS10 domain-containing receptor SorCS3	Plays an important role in modulating synaptic transmission and plasticity in the hippocampus, probably by affecting the trafficking and localization ofAMPA-type glutamate receptors in the postsynaptic density.
COLEC11	Collectin-11	Lectin that plays a role in innate immunity, apoptosis and embryogenesis.
ALLC	Probable inactive allantoicase	The function of this enzyme is unclear as allantoicase activity is not known to exist in mammals.
KCNH7	Voltage-gated inwardly rectifying potassium channel KCNH7	Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel.
CHAT	Choline O-acetyltransferase	Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses.
SASH1	SAM and SH3 domain-containing protein 1	Is a positive regulator of NF-kappa-B signaling downstream of TLR4 activation.
SCAF8	SR-related and CTD-associated factor 8	Anti-terminator protein required to prevent early mRNA termination during transcription.
COL4A3	Collagen alpha-3(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
MED13L	Mediator of RNA polymerase II transcription subunit 13-like	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
CNKSR3	Connector enhancer of kinase suppressor of ras 3	Involved in transepithelial sodium transport.
ABTB3	Ankyrin repeat- and BTB/POZ domain-containing protein 3	Cortical and hippocampal inhibitory interneuron-specific protein localized at glutamatergic (excitatory) synapses, where it supports cell type-specific synaptic function.
FTO	Alpha-ketoglutarate-dependent dioxygenase FTO	RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis.
KDM4D	Lysine-specific demethylase 4D	Histone demethylase that specifically demethylates ‘Lys-9’ of histone H3, thereby playing a central role in histone code.
MCTP2	Multiple C2 and transmembrane domain-containing protein 2	Might play a role in the development of cardiac outflow tract.
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).
CGNL1	Cingulin-like protein 1	May be involved in anchoring the apical junctional complex, especially tight junctions, to actin-based cytoskeletons.
MSRB3	Methionine-R-sulfoxide reductase B3	Catalyzes the reduction of free and protein-bound methionine sulfoxide to methionine.
COQ5	2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial	Methyltransferase required for the conversion of 2-decaprenyl-6-methoxy-1,4-benzoquinol (DDMQH2) to 2-decaprenyl-3-methyl-6-methoxy-1,4-benzoquinol (DMQH2).
WWC1	Protein KIBRA	Regulator of the Hippo signaling pathway, also known as the Salvador-Warts-Hippo (SWH) pathway.
RGMA	Repulsive guidance molecule A	Member of the repulsive guidance molecule (RGM) family that performs several functions in the developing and adult nervous system.
TBC1D31	TBC1 domain family member 31	Molecular adapter which is involved in cilium biogenesis.
PRCD	Photoreceptor disk component PRCD	Involved in vision.
ERBB4	Receptor tyrosine-protein kinase erbB-4	Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell prolife…
GABRR1	Gamma-aminobutyric acid receptor subunit rho-1	Rho subunit of the pentameric ligand-gated chloride channels responsible for mediating the effects of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain.
TRABD2B	Metalloprotease TIKI2	Metalloprotease that acts as a negative regulator of the Wnt signaling pathway by mediating the cleavage of the 8 N-terminal residues of a subset of Wnt proteins.
HMGA2	High mobility group protein HMGI-C	Functions as a transcriptional regulator.
ANXA11	Annexin A11	Binds specifically to calcyclin in a calcium-dependent manner.
ITGA6	Integrin alpha-6	Integrin alpha-6/beta-1 (ITGA6:ITGB1) is a receptor for laminin on platelets.
APOL1	Apolipoprotein L1	May play a role in lipid exchange and transport throughout the body.
ITPR1	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR1	Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER).
AFF3	AF4/FMR2 family member 3	Putative transcription activator that may function in lymphoid development and oncogenesis.
LIMK2	LIM domain kinase 2	Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics.
LRP8	Low-density lipoprotein receptor-related protein 8	Cell surface receptor for Reelin (RELN) and apolipoprotein E (apoE)-containing ligands.
MAT1A	S-adenosylmethionine synthase isoform type-1	Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
MUC7	Mucin-7	May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing.
MYH9	Myosin-9	Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.
NRG3	Pro-neuregulin-3, membrane-bound isoform	Direct ligand for the ERBB4 tyrosine kinase receptor.
AUH	Methylglutaconyl-CoA hydratase, mitochondrial	Catalyzes the fifth step in the leucine degradation pathway, the reversible hydration of 3-methylglutaconyl-CoA (3-MG-CoA) to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA).

Protein-family classification

Druggable: 17 · Difficult: 12 · Unknown: 30 · Druggable fraction: 0.29

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
Scaffold/PPI	9	2.6×	0.052
Enzyme (other)	9	1.8×	0.218
Ion channel	2	3.8×	0.262
Antibody/Immunoglobulin	3	1.5×	0.658
Phosphatase	1	1.4×	0.812
Kinase	2	0.9×	0.844
Other/Unknown	30	0.9×	0.933
Transcription factor	3	0.4×	0.980

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNF10	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
RPS12	Other/Unknown	no		Ribosomal_eS12, Ribosomal_eL8/eL30/eS12/Gad45, Ribosomal_eL30-like_sf
SNCAIP	Scaffold/PPI	no		Ankyrin_rpt, SNCAIP_SNCA-bd, Ankyrin_rpt-contain_sf
SOX11	Transcription factor	no		HMG_box_dom, SOX-12/11/4, HMG_box_dom_sf
STAC	Scaffold/PPI	no		SH3_domain, PKC_DAG/PE, STAC1_SH3
SUCLG2	Enzyme (other)	yes	6.2.1.4	Succ_CoA_ligase-like_bsu, SUCC_ACL_C, ATP-grasp_succ-CoA_synth-type
TNFRSF19	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFR_19, TNFRSF19_N
XRCC2	Other/Unknown	no		Rad51_C, RecA_ATP-bd, P-loop_NTPase
CNTNAP2	Other/Unknown	no		FA58C, EGF, Laminin_G
SORBS1	Scaffold/PPI	no		SH3_domain, SoHo_dom, SORBS1_SH3
NAV3	Other/Unknown	no		CH_dom, AAA+_ATPase, ATPase_AAA_core
ELMO1	Scaffold/PPI	no		PH_domain, ELMO_dom, ARM-like
SORCS3	Antibody/Immunoglobulin	yes		PKD_dom, VPS10, Ig-like_fold
COLEC11	Other/Unknown	no		C-type_lectin-like, Collagen, C-type_lectin-like/link_sf
ALLC	Other/Unknown	no		Allantoicase, Galactose-bd-like_sf, Allantoicase_dom
KCNH7	Ion channel	yes		PAS, cNMP-bd_dom, K_chnl_volt-dep_EAG/ELK/ERG
CHAT	Enzyme (other)	yes	2.3.1.6	Carn_acyl_trans, CAT-like_dom_sf, Cho/carn_acyl_trans_1_2
SASH1	Transcription factor	no		SH3_domain, SAM, SAM/pointed_sf
SCAF8	Other/Unknown	no		RRM_dom, CID_dom, ENTH_VHS
COL4A3	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
MED13L	Other/Unknown	no		Med13_C, Mediator_Med13_N, MID_MedPIWI
CNKSR3	Scaffold/PPI	no		PDZ, SAM, CNK2/3_dom
ABTB3	Scaffold/PPI	no		BTB/POZ_dom, Ankyrin_rpt, Histone-fold
FTO	Enzyme (other)	yes	1.14.11.53	FTO_C, FTO_cat_dom, FTO
GRAMD2B	Other/Unknown	no		GRAM, PH-like_dom_sf, GRAM_domain_protein_2B
KDM4D	Enzyme (other)	yes	1.14.11.27	JmjC_dom, JmjN
MCTP2	Other/Unknown	no		C2_dom, MCTP_C, C2_domain_sf
TTC21B	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC21A/TTC21B
CGNL1	Other/Unknown	no		Myosin_tail
TTC39C	Other/Unknown	no		TPR-like_helical_dom_sf, IML2/TPR_39
IGSF22	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
SMIM13	Other/Unknown	no		DUF4750
MSRB3	Enzyme (other)	yes	1.8.4.12	Met_Sox_Rdtase_MsrB_dom, Mss4-like_sf, Met_Sox_Rdtase_MsrB
COQ5	Enzyme (other)	yes	2.1.1.201	UbiE/COQ5_MeTrFase, UbiE/COQ5_MeTrFase_CS, SAM-dependent_MTases_sf
WWC1	Scaffold/PPI	no		C2_dom, WW_dom, C2_domain_sf
RGMA	Other/Unknown	no		RGM_C, RGM_N, RGM
TBC1D31	Scaffold/PPI	no		Rab-GAP-TBC_dom, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
PRCD	Other/Unknown	no		PRCD
ERBB4	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
GABRR1	Other/Unknown	no		GABAA/Glycine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
TRABD2B	Other/Unknown	no		TraB/PrgY/GumN_fam, TIKI1/2-like
GUCY1A1	Enzyme (other)	yes	4.6.1.2	A/G_cyclase, HNOB_dom_associated, A/G_cyclase_CS
PRNCR1	Other/Unknown	no
HMGA2	Other/Unknown	no		HMGA, HMGI/Y_DNA-bd_CS, AT_hook_DNA-bd_motif
LINC01266	Other/Unknown	no
ANXA11	Other/Unknown	no		Annexin, ANX11, Annexin_repeat_CS
ITGA6	Antibody/Immunoglobulin	yes		Integrin_alpha, FG-GAP, Int_alpha_beta-p
APOL1	Other/Unknown	no		ApoL
ITPR1	Ion channel	yes		InsP3_rcpt, RIH_dom, Ion_trans_dom
AFF3	Other/Unknown	no		AF4/FMR2, AF4_int, AF4/FMR2_CHD

Expression context

Cohort genes with no expression data: 0.

53 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)	1
broad (>20)	58
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	7
male germ line stem cell (sensu Vertebrata) in testis	6
primordial germ cell in gonad	5
buccal mucosa cell	5
ganglionic eminence	4
ventricular zone	4
liver	4
right lobe of liver	4
secondary oocyte	4
lower esophagus mucosa	3
saphenous vein	3
Brodmann (1909) area 23	3
middle temporal gyrus	3
pigmented layer of retina	3
calcaneal tendon	3
esophagus squamous epithelium	3
parotid gland	3
urethra	3
sural nerve	3
left testis	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF10	290	ubiquitous	marker	left testis, right testis, lower esophagus mucosa
RPS12	153	ubiquitous	marker	left ovary, primordial germ cell in gonad, ovary
SNCAIP	240	broad	marker	ventricular zone, ganglionic eminence, germinal epithelium of ovary
SOX11	93	broad	marker	ganglionic eminence, cortical plate, embryo
STAC	191	ubiquitous	marker	dorsal root ganglion, periodontal ligament, trigeminal ganglion
SUCLG2	286	ubiquitous	marker	colonic mucosa, mucosa of sigmoid colon, rectum
TNFRSF19	224	ubiquitous	marker	upper arm skin, upper leg skin, bronchial epithelial cell
XRCC2	283	ubiquitous	marker	buccal mucosa cell, tendon of biceps brachii, lateral globus pallidus
CNTNAP2	127	broad	marker	corpus callosum, superior frontal gyrus, C1 segment of cervical spinal cord
SORBS1	287	ubiquitous	marker	blood vessel layer, saphenous vein, left ventricle myocardium
NAV3	232	ubiquitous	marker	middle temporal gyrus, cortical plate, Brodmann (1909) area 23
ELMO1	248	ubiquitous	marker	prefrontal cortex, C1 segment of cervical spinal cord, corpus callosum
SORCS3	118	broad	marker	ventricular zone, cortical plate, Brodmann (1909) area 10
COLEC11	180	tissue_specific	marker	right lobe of liver, gall bladder, liver
ALLC	139	tissue_specific	marker	sperm, male germ cell, right testis
KCNH7	90	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, pancreatic ductal cell, ventricular zone
CHAT	68	tissue_specific	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, putamen
SASH1	293	ubiquitous	marker	synovial joint, lateral globus pallidus, skin of hip
SCAF8	294	ubiquitous	marker	secondary oocyte, oocyte, sperm
COL4A3	233	broad	marker	skeletal muscle tissue of biceps brachii, pigmented layer of retina, retina
MED13L	297	ubiquitous	marker	calcaneal tendon, colonic epithelium, tendon
CNKSR3	242	ubiquitous	marker	esophagus squamous epithelium, pigmented layer of retina, ileal mucosa
ABTB3	205	ubiquitous	marker	lower esophagus mucosa, esophagus squamous epithelium, upper arm skin
FTO	294	ubiquitous	marker	cortical plate, bronchial epithelial cell, Brodmann (1909) area 10
GRAMD2B	282	ubiquitous	marker	calcaneal tendon, medial globus pallidus, globus pallidus
KDM4D	161	broad	yes	buccal mucosa cell, left testis, testis
MCTP2	234	broad	marker	germinal epithelium of ovary, secondary oocyte, buccal mucosa cell
TTC21B	179	ubiquitous	marker	right uterine tube, calcaneal tendon, cerebellar hemisphere
CGNL1	234	ubiquitous	marker	kidney epithelium, parotid gland, renal medulla
TTC39C	237	ubiquitous	marker	right lobe of liver, liver, oviduct epithelium

Protein interactions among cohort

Intra-cohort edges: 10.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SUCLG2	6,231
MYH9	5,533
RPS12	4,627
ERBB4	4,325
ITPR1	3,483
ITGA6	3,130
MAT1A	3,118
SCAF8	3,029
RAD51B	2,993
LIMK2	2,649

Intra-cohort edges

A	B	Sources
AFF3	MCTP2	string_interaction
APOL1	GUCY1A1	string_interaction
APOL1	MYH9	string_interaction
CNKSR3	SCAF8	string_interaction
COL4A3	MYH9	string_interaction
COQ5	RNF10	string_interaction
ERBB4	NRG3	string_interaction
MCTP2	RGMA	string_interaction
RAD51B	XRCC2	biogrid_interaction, intact, string_interaction
SORBS1	STAC	string_interaction

Structural data

PDB: 35 · AlphaFold-only: 22 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KDM4D	Q6B0I6	284
RPS12	P25398	198
FTO	Q9C0B1	28
GABRR1	P24046	26
ELMO1	Q92556	18
XRCC2	O43543	16
ERBB4	Q15303	14
GUCY1A1	Q02108	12
PTPN13	Q12923	12
SORBS1	Q9BX66	11
SCAF8	Q9UPN6	10
CHAT	P28329	8
MYH9	P35579	8
LIMK2	P53671	7
SUCLG2	Q96I99	6
WWC1	Q8IX03	5
APOL1	O14791	5
RAD51B	O15315	5
SOX11	P35716	4
LRP8	Q14114	4
MAT1A	Q00266	4
COLEC11	Q9BWP8	3
TTC21B	Q7Z4L5	3
AUH	Q13825	3
STAC	Q99469	2
SASH1	O94885	2
COL4A3	Q01955	2
MSRB3	Q8IXL7	2
RGMA	Q96B86	2
ANXA11	P50995	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ALLC	Q8N6M5	91.83
TTC39C	Q8N584	85.75
IGSF22	Q8N9C0	85.34
COQ5	Q5HYK3	82.86
TBC1D31	Q96DN5	76.36
SORCS3	Q9UPU3	75.70
ABTB3	A6QL63	73.18
TRABD2B	A6NFA1	70.11
SMIM13	P0DJ93	69.34
RNF10	Q8N5U6	65.67
HMGA2	P52926	65.46
PRCD	Q00LT1	65.20
CNKSR3	Q6P9H4	64.67
CGNL1	Q0VF96	64.25
GRAMD2B	Q96HH9	63.97
TNFRSF19	Q9NS68	60.50
MED13L	Q71F56	56.79
MUC7	Q8TAX7	55.60
AFF3	P51826	52.20
NRG3	P56975	50.59
NAV3	Q8IVL0	48.21
ITPR1	Q14643

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 257. Enrichment computed across 59 evidence-associated genes (34 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 34 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective MAT1A causes MATD	1	335.9×	0.035	MAT1A
3-methylglutaconic aciduria	1	335.9×	0.035	AUH
PI3K events in ERBB4 signaling	2	61.1×	0.035	ERBB4, NRG3
Nitric oxide stimulates guanylate cyclase	2	48.0×	0.035	GUCY1A1, ITPR1
ERBB2 Activates PTK6 Signaling	2	48.0×	0.035	ERBB4, NRG3
SHC1 events in ERBB4 signaling	2	42.0×	0.035	ERBB4, NRG3
ERBB2 Regulates Cell Motility	2	42.0×	0.035	ERBB4, NRG3
PI3K events in ERBB2 signaling	2	39.5×	0.035	ERBB4, NRG3
Sema4D in semaphorin signaling	2	39.5×	0.035	LIMK2, MYH9
GRB2 events in ERBB2 signaling	2	37.3×	0.035	ERBB4, NRG3
RHO GTPases Activate ROCKs	2	35.4×	0.035	LIMK2, MYH9
Sema4D induced cell migration and growth-cone collapse	2	33.6×	0.035	LIMK2, MYH9
SHC1 events in ERBB2 signaling	2	28.0×	0.035	ERBB4, NRG3
Signaling by ERBB2 TMD/JMD mutants	2	28.0×	0.035	ERBB4, NRG3
Impaired BRCA2 binding to PALB2	2	26.9×	0.035	XRCC2, RAD51B
Signaling by ERBB2 KD Mutants	2	24.9×	0.035	ERBB4, NRG3
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	2	24.9×	0.035	XRCC2, RAD51B
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	2	24.9×	0.035	XRCC2, RAD51B
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	2	24.9×	0.035	XRCC2, RAD51B
Semaphorin interactions	2	23.2×	0.035	LIMK2, MYH9
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	2	23.2×	0.035	XRCC2, RAD51B
Anti-inflammatory response favouring Leishmania parasite infection	2	23.2×	0.035	ITPR1, MYH9
Leishmania parasite growth and survival	2	23.2×	0.035	ITPR1, MYH9
Laminin interactions	2	22.4×	0.035	COL4A3, ITGA6
Homologous DNA Pairing and Strand Exchange	2	22.4×	0.035	XRCC2, RAD51B
Downregulation of ERBB2 signaling	2	22.4×	0.035	ERBB4, NRG3
Signaling by ERBB2	2	20.4×	0.039	ERBB4, NRG3
Nuclear signaling by ERBB4	2	20.4×	0.039	ERBB4, NRG3
Resolution of D-loop Structures through Holliday Junction Intermediates	2	17.7×	0.050	XRCC2, RAD51B
Fcgamma receptor (FCGR) dependent phagocytosis	2	16.4×	0.054	ITPR1, MYH9

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 54 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cytokinetic process	2	208.1×	0.013	ANXA11, MYH9
ERBB4 signaling pathway	2	104.0×	0.031	ERBB4, NRG3
ERBB4-ERBB4 signaling pathway	2	89.2×	0.031	ERBB4, NRG3
negative regulation of neuron migration	2	52.0×	0.068	ERBB4, NRG3
cornea development in camera-type eye	2	48.0×	0.068	SOX11, LIMK2
allantoin catabolic process	1	312.1×	0.071	ALLC
mesodermal-endodermal cell signaling	1	312.1×	0.071	HMGA2
L-methionine catabolic process	1	312.1×	0.071	MAT1A
ammon gyrus development	1	312.1×	0.071	LRP8
chemorepulsion involved in interneuron migration from the subpallium to the cortex	1	312.1×	0.071	NRG3
regulation of white fat cell proliferation	1	312.1×	0.071	FTO
retrograde trans-synaptic signaling by nitric oxide, modulating synaptic transmission	1	312.1×	0.071	GUCY1A1
regulation of protein K63-linked ubiquitination	1	312.1×	0.071	SASH1
regulation of protein autoubiquitination	1	312.1×	0.071	SASH1
negative regulation of transcription regulatory region DNA binding	1	312.1×	0.071	SOX11
central nervous system morphogenesis	1	156.0×	0.071	ERBB4
limbic system development	1	156.0×	0.071	CNTNAP2
uropod organization	1	156.0×	0.071	MYH9
cortical granule exocytosis	1	156.0×	0.071	MYH9
closure of optic fissure	1	156.0×	0.071	SOX11
superior temporal gyrus development	1	156.0×	0.071	CNTNAP2
establishment of planar polarity involved in nephron morphogenesis	1	156.0×	0.071	ERBB4
regulation of inclusion body assembly	1	156.0×	0.071	SNCAIP
release of sequestered calcium ion into cytosol by endoplasmic reticulum	1	156.0×	0.071	ITPR1
negative regulation of actin filament severing	1	156.0×	0.071	MYH9
positive regulation of protein processing in phagocytic vesicle	1	156.0×	0.071	MYH9
negative regulation of excitatory synapse assembly	1	156.0×	0.071	PTPN13
regulation of intraciliary retrograde transport	1	156.0×	0.071	TTC21B
negative regulation of termination of RNA polymerase II transcription, poly(A)-coupled	1	156.0×	0.071	SCAF8
positive regulation of lens epithelial cell proliferation	1	156.0×	0.071	SOX11

Therapeutics

Drugs indicated for this disease

2 approved, 23 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Captopril	Approved (phase 4)
Irbesartan	Approved (phase 4)
Atrasentan	Phase 3 (in late-stage trials)
Avosentan	Phase 3 (in late-stage trials)
Bardoxolone Methyl	Phase 3 (in late-stage trials)
Calcitriol	Phase 3 (in late-stage trials)
Empagliflozin	Phase 3 (in late-stage trials)
Fexofenadine	Phase 3 (in late-stage trials)
Finerenone	Phase 3 (in late-stage trials)
Ivabradine	Phase 3 (in late-stage trials)
Liraglutide	Phase 3 (in late-stage trials)
Lisinopril Anhydrous	Phase 3 (in late-stage trials)
Losartan	Phase 3 (in late-stage trials)
Montelukast	Phase 3 (in late-stage trials)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Niclosamide	Phase 3 (in late-stage trials)
Nifedipine	Phase 3 (in late-stage trials)
Olmesartan Medoxomil	Phase 3 (in late-stage trials)
Pyridoxamine Dihydrochloride	Phase 3 (in late-stage trials)
Ramipril	Phase 3 (in late-stage trials)
Roflumilast	Phase 3 (in late-stage trials)
Simvastatin	Phase 3 (in late-stage trials)
Sirolimus	Phase 3 (in late-stage trials)
Sulodexide	Phase 3 (in late-stage trials)
Telmisartan	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aliskiren, Azeliragon, Baricitinib, Calcium Carbonate, Colchicine, Corticotropin, Dapagliflozin, Duloxetine, Eplerenone, Fenofibrate, Folic Acid, Fosinopril, Hydrochlorothiazide, Insulin Human, Levocetirizine, Magnesium Citrate, Milk Thistle, Paricalcitol, Pentoxifylline, Probucol, Selonsertib, Semaglutide, Sitokiren, Tozorakimab, Trimetazidine, Valsartan, Vinpocetine, XL550.

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 7 · Phased (≥1): 11 · Undrugged: 48

Druggability breadth: 24 of 59 evidence-associated genes (41%) 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
RPS12	GENTAMICIN SULFATE
FTO	FLUORESCEIN
ERBB4	MOBOCERTINIB
GABRR1	LINDANE
GUCY1A1	BENZYDAMINE
LIMK2	DASATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ERBB4	47	4
LIMK2	23	4
FTO	18	4
GABRR1	5	4
GUCY1A1	2	4
RPS12	1	4
ELMO1	1	2
CHAT	1	3
KDM4D	1	2
MSRB3	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPS12
FLUORESCEIN	4	FTO
DEMECLOCYCLINE	4	FTO
ROXADUSTAT	4	FTO
MECLOFENAMIC ACID	4	FTO
AMILORIDE	4	FTO
TACRINE	4	FTO
ENTACAPONE	4	FTO
MOBOCERTINIB	4	ERBB4
AFATINIB	4	ERBB4
FEDRATINIB	4	ERBB4, LIMK2
NERATINIB	4	ERBB4
IBRUTINIB	4	ERBB4
AFATINIB DIMALEATE	4	ERBB4
DACOMITINIB	4	ERBB4
DACOMITINIB ANHYDROUS	4	ERBB4
VANDETANIB	4	ERBB4
BOSUTINIB	4	ERBB4
BRIGATINIB	4	ERBB4
ACALABRUTINIB	4	ERBB4
ZANUBRUTINIB	4	ERBB4
TIRABRUTINIB	4	ERBB4
RITLECITINIB	4	ERBB4
DASATINIB	4	ERBB4, LIMK2
ERLOTINIB	4	ERBB4
LAPATINIB	4	ERBB4
MIDOSTAURIN	4	ERBB4
GEFITINIB	4	ERBB4
LINDANE	4	GABRR1
AMINOLEVULINIC ACID	4	GABRR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 12.

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

Symbol	Assays	Type breakdown
ERBB4	591	Binding:579, ADMET:8, Functional:4
LIMK2	191	Binding:191
FTO	153	Binding:153
RPS12	90	Binding:90
GABRR1	55	Binding:29, Functional:26
GUCY1A1	45	Binding:40, Functional:5
KDM4D	43	Binding:41, Functional:2
PTPN13	23	Binding:22, ADMET:1
KCNH7	21	Binding:20, Toxicity:1
ITPR1	13	Binding:12, Functional:1
MYH9	10	Binding:10
CHAT	7	Binding:7
MSRB3	7	Binding:6, ADMET:1
ANXA11	7	Binding:7
ELMO1	6	Binding:6
APOL1	4	Binding:4
MAT1A	4	Binding:4
ITGA6	3	Binding:3
RNF10	1	Binding:1
SNCAIP	1	Binding:1
SUCLG2	1	Binding:1
SORBS1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SUCLG2	6.2.1.4	succinate-CoA ligase (GDP-forming)
CHAT	2.3.1.6	choline O-acetyltransferase
FTO	1.14.11.53	mRNA N6-methyladenine demethylase
KDM4D	1.14.11.27, 1.14.11.66	[histone H3]-dimethyl-L-lysine36 demethylase, [histone H3]-trimethyl-L-lysine9 demethylase
MSRB3	1.8.4.12, 1.8.4.B3	peptide-methionine (R)-S-oxide reductase,
COQ5	2.1.1.201	2-methoxy-6-polyprenyl-1,4-benzoquinol methylase
ERBB4	2.7.10.1	receptor protein-tyrosine kinase
GUCY1A1	4.6.1.2	guanylate cyclase
LIMK2	2.7.10.2	non-specific protein-tyrosine kinase
MAT1A	2.5.1.6	methionine adenosyltransferase
AUH	4.2.1.18	methylglutaconyl-CoA hydratase
PTPN13	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
FTO	153
ERBB4	591
LIMK2	191

Pharmacogenomics

Cohort genes with a PharmGKB record: 57; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
GENTAMICIN SULFATE	4	RPS12
FLUORESCEIN	4	FTO
DEMECLOCYCLINE	4	FTO
ROXADUSTAT	4	FTO
MECLOFENAMIC ACID	4	FTO
AMILORIDE	4	FTO
TACRINE	4	FTO
ENTACAPONE	4	FTO
MOBOCERTINIB	4	ERBB4
AFATINIB	4	ERBB4
FEDRATINIB	4	ERBB4, LIMK2
NERATINIB	4	ERBB4
IBRUTINIB	4	ERBB4
AFATINIB DIMALEATE	4	ERBB4
DACOMITINIB	4	ERBB4
DACOMITINIB ANHYDROUS	4	ERBB4
VANDETANIB	4	ERBB4
BOSUTINIB	4	ERBB4
BRIGATINIB	4	ERBB4
ACALABRUTINIB	4	ERBB4
ZANUBRUTINIB	4	ERBB4
TIRABRUTINIB	4	ERBB4
RITLECITINIB	4	ERBB4
DASATINIB	4	ERBB4, LIMK2
ERLOTINIB	4	ERBB4
LAPATINIB	4	ERBB4
MIDOSTAURIN	4	ERBB4
GEFITINIB	4	ERBB4
LINDANE	4	GABRR1
AMINOLEVULINIC ACID	4	GABRR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	6	RPS12, FTO, ERBB4, GABRR1, GUCY1A1, LIMK2
B	Phased (≥1) drug, not yet approved	5	ELMO1, CHAT, KDM4D, MSRB3, MYH9
C	Druggable family + PDB, no drug	6	SUCLG2, KCNH7, ITGA6, MAT1A, AUH, PTPN13
D	Druggable family + AlphaFold only, no drug	4	SORCS3, IGSF22, COQ5, ITPR1
E	Difficult family or no structure, no drug	38	RNF10, SNCAIP, SOX11, STAC, TNFRSF19, XRCC2, CNTNAP2, SORBS1, NAV3, COLEC11 (+28 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
APOL1	4	MYH9
NRG3	0	ERBB4
RNF10	1	—
SNCAIP	1	—
SOX11	0	—
STAC	0	—
SUCLG2	1	—
TNFRSF19	0	—
XRCC2	0	—
CNTNAP2	0	—
SORBS1	1	—
NAV3	0	—
SORCS3	0	—
COLEC11	0	—
ALLC	0	—
KCNH7	21	—
SASH1	0	—
SCAF8	0	—
COL4A3	0	—
MED13L	0	—
CNKSR3	0	—
ABTB3	0	—
GRAMD2B	0	—
MCTP2	0	—
TTC21B	0	—
CGNL1	0	—
TTC39C	0	—
IGSF22	0	—
SMIM13	0	—
COQ5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 446.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	204
PHASE2	94
PHASE4	58
PHASE3	37
PHASE1	18
PHASE2/PHASE3	15
PHASE1/PHASE2	15
EARLY_PHASE1	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03625648	PHASE4	ACTIVE_NOT_RECRUITING	Pentoxifylline in Diabetic Kidney Disease
NCT06291155	PHASE4	RECRUITING	Mechanism of SGLT2 Inhibition in the Kidney
NCT06431477	PHASE4	RECRUITING	Efficacy and Safety of Telmisartan Compared With Losartan
NCT06532682	PHASE4	ACTIVE_NOT_RECRUITING	Efficacy of Dapagliflozin in Early Diabetic Nephropathy in Type 1 Diabetes
NCT06660940	PHASE4	NOT_YET_RECRUITING	Clinical Trial of Keluoxin Capsules in the Treatment of Diabetic Kidney Disease with Diabetic Retinopathy
NCT06954090	PHASE4	ENROLLING_BY_INVITATION	Urinary Proteomics to Guide Early Intervention to Prevent Complications in Type 2 Diabetes - a Feasibility Study
NCT07155694	PHASE4	NOT_YET_RECRUITING	Role of Finerenone in African American Veterans With Diabetic Kidney Disease
NCT07187713	PHASE4	RECRUITING	ACE Reno, Pico Cell Matrix and Its Effect on eGFR in Chronic Kidney Diseases
NCT07523867	PHASE4	NOT_YET_RECRUITING	Spironolactone Alternate Dosing vs Finerenone in Elevated Potassium - K Safety Study
NCT00130312	PHASE4	TERMINATED	Effect of Sulodexide in Overt Diabetic Nephropathy
NCT00153023	PHASE4	COMPLETED	1 Year Trial Telmisartan 80 mg Versus Valsartan 160 mg in Hypertensive Type 2 Diabetic Patients With Overt Nephropathy
NCT00153088	PHASE4	COMPLETED	INNOVATION Study - Telmisartan (Micardis) in Incipient Diabetic Nephropathy
NCT00168857	PHASE4	COMPLETED	A Prospective, Randomised, Double-blind, Double-dummy, Forced-titration, Multicentre, Parallel Group, One Year Treatment Trial to Compare Telmisartan (MICARDIS) 80 mg Versus Losartan (COZAAR) 100 mg, in Hypertensive Type 2 Diabetic Patients With Overt Nephropathy (AMADEO Study)
NCT00171119	PHASE4	TERMINATED	A Study in Patients With Diabetes Mellitus Type II of the Effect on Albuminuria of 24 Week Treatment With Valsartan, Benazepril, and Valsartan+Benazepril
NCT00171574	PHASE4	COMPLETED	Antiproteinuric Effect of Valsartan and Lisinopril
NCT00171600	PHASE4	TERMINATED	Antialbuminuric Effects of Valsartan and Lisinopril
NCT00296296	PHASE4	COMPLETED	Immunosuppression Impact on the Metabolic Control of Kidney Transplant With Pre-Existing Type 2 Diabetes (DM)
NCT00311870	PHASE4	COMPLETED	Renoprotective Effect of Nisoldipine and Lisinopril in Type 1 Diabetic Nephropathy
NCT00317954	PHASE4	COMPLETED	Spironolactone in Diabetic Nephropathy
NCT00363987	PHASE4	COMPLETED	Controlled Study to Evaluate Efficacy and Safety of α-KA Tab With Low Protein Diet (LPD) in Delaying the Progress of Type 2 Diabetic Nephropathy (DN)
NCT00438503	PHASE4	COMPLETED	Glucose in Dialysis Water in Diabetics With Chronic Renal Failure
NCT00535925	PHASE4	COMPLETED	Nephropathy In Type 2 Diabetes and Cardio-renal Events
NCT00565318	PHASE4	COMPLETED	Benfotiamine in Diabetic Nephropathy
NCT00870402	PHASE4	UNKNOWN	Aldosterone in Diabetic Nephropathy
NCT00893425	PHASE4	COMPLETED	Effect of Renin Angiotensin System Blockade on the Fas Antigen (CD95) and Asymmetric Dimethylarginine (ADMA) Levels in Type-2 Diabetic Patients With Proteinuria
NCT01028287	PHASE4	COMPLETED	Adrenocorticotropic Hormone (ACTH) Treatment of Nephrotic Range Proteinuria in Diabetic Nephropathy (NRDN)
NCT01094769	PHASE4	COMPLETED	Sympathetic Nervous System Inhibition for the Treatment of Diabetic Kidney Disease
NCT01129557	PHASE4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT01252056	PHASE4	COMPLETED	A Clinical Study to Evaluate the Efficacy and Safety of Cilostazol and Probucol in Combination on Patients With Diabetic Nephropathy
NCT01316068	PHASE4	UNKNOWN	Effect of Sulodexide on Albuminuria in Chinese Type 2 Diabetic Patients
NCT01331317	PHASE4	COMPLETED	Effect of a Vitamin D Analogue vs Placebo on p-NT-proBNP in Patients With Type 1 DM and Diabetic Nephropathy
NCT01588795	PHASE4	COMPLETED	Renal Denervation in Diabetic Nephropathy
NCT01673204	PHASE4	UNKNOWN	Clinical Trial Technology Development for the Validation of Surrogate Prognostic Markers in Patients With Diabetic Nephropathy
NCT01703234	PHASE4	COMPLETED	FGF-23 and Endothelial Dysfunction in Diabetic Proteinuric Patients
NCT01725412	PHASE4	UNKNOWN	Prevention of Renal Complications of Diabetes With Thiamine
NCT01743014	PHASE4	UNKNOWN	Ramipril and Clopidogrel in Oxidative Stress, Vascular Inflammation and Endothelial Dysfunction in Type 2 Diabetes and Diabetic Nephropathy
NCT01869881	PHASE4	COMPLETED	Effect of Sarpogrelate On the Nephropathy in Type 2 Diabetes (SONATA Study)
NCT02276196	PHASE4	COMPLETED	Effect of LIXIsenatide on the Renal System
NCT02502071	PHASE4	COMPLETED	Effect of Urinary Alkalinization on Urine Uric Acid Precipitation and Crystallization in Adults With Type 1 Diabetes
NCT02545738	PHASE4	COMPLETED	Antiproteinuric Effects of Liraglutide Treatment

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LISINOPRIL ANHYDROUS	4	12
LOSARTAN	4	10
CANAGLIFLOZIN ANHYDROUS	4	9
ENALAPRIL	4	9
AMINOHIPPURIC ACID	4	8
FINERENONE	4	8
RAMIPRIL	4	5
SPIRONOLACTONE	4	5
TELMISARTAN	4	5
VALSARTAN	4	5
ERTUGLIFLOZIN	4	4
IRBESARTAN	4	4
CALCITRIOL	4	3
EMPAGLIFLOZIN	4	3
FENOFIBRATE	4	3
OLMESARTAN MEDOXOMIL	4	3
PENTOXIFYLLINE	4	3
PIRFENIDONE	4	3
ALLOPURINOL	4	2
CALCIUM CARBONATE	4	2
CLONIDINE	4	2
EPLERENONE	4	2
PARICALCITOL	4	2
PROBUCOL	4	2
SEVELAMER CARBONATE	4	2
SIMVASTATIN	4	2
SOTAGLIFLOZIN	4	2
TACROLIMUS ANHYDROUS	4	2
ACETYLCYSTEINE	4	1
ALISKIREN	4	1

Cohort genes: RNF10, RPS12, SNCAIP, SOX11, STAC, SUCLG2, TNFRSF19, XRCC2, CNTNAP2, SORBS1, NAV3, ELMO1, SORCS3, COLEC11, ALLC, KCNH7, CHAT, SASH1, SCAF8, COL4A3, MED13L, CNKSR3, ABTB3, FTO, GRAMD2B, KDM4D, MCTP2, TTC21B, CGNL1, TTC39C, IGSF22, SMIM13, MSRB3, COQ5, WWC1, RGMA, TBC1D31, PRCD, ERBB4, GABRR1, TRABD2B, GUCY1A1, PRNCR1, HMGA2, LINC01266, ANXA11, ITGA6, APOL1, ITPR1, AFF3, LIMK2, LRP8, MAT1A, MUC7, MYH9, NRG3, AUH, PTPN13, RAD51B
Drugs: Lisinopril, Losartan, Canagliflozin, Enalapril, Aminohippuric Acid, Finerenone, Ramipril, Spironolactone, Telmisartan, Valsartan, Ertugliflozin, Irbesartan, Calcitriol, Empagliflozin, Fenofibrate, Olmesartan Medoxomil, Pentoxifylline, Pirfenidone, Allopurinol, Calcium Carbonate, Clonidine, Eplerenone, Paricalcitol, Probucol, Sevelamer Carbonate, Simvastatin, Sotagliflozin, Tacrolimus, Acetylcysteine, Aliskiren