Non-immune hydrops fetalis

Summary

Non-immune hydrops fetalis (MONDO:0009369) is a disease caused by variants in THSD1 and EHBP1L1, with 43 cohort genes and 2 clinical trials.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal genes: THSD1 (GenCC Definitive), EHBP1L1 (GenCC Strong)
• Cohort genes: 43
• ClinVar variants: 63
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	>1 / 1000	300	Thailand	Validated
Prevalence at birth	1-5 / 10 000	42	Worldwide	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	non-immune hydrops fetalis
Mondo ID	MONDO:0009369
OMIM	236750
Orphanet	363999
ICD-11	1182287637
NCIT	C111905
SNOMED CT	276509008
UMLS	C0455988
MedGen	105327
GARD	0017580
Is cancer (heuristic)	no

Also known as: Haemoglobin H hydrops fetalis syndrome · hydrops fetalis, nonimmune · NIHF · non-immune fetal edema · non-immune fetal hydrops · non-immune foetal hydrops · non-immune foetal oedema · non-immune HF

Data availability: 63 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › hydrops fetalis › non-immune hydrops fetalis

Related subtypes (1): immune hydrops fetalis

Subtypes (1): Hb Bart’s hydrops fetalis

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

63 retrieved; paginated sample, class counts are floors:

16 pathogenic, 15 uncertain significance, 12 pathogenic/likely pathogenic, 10 likely pathogenic, 9 conflicting classifications of pathogenicity, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065494	NM_001100.4(ACTA1):c.226G>C (p.Gly76Arg)	ACTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065491	NM_006015.6(ARID1A):c.175G>T (p.Glu59Ter)	ARID1A	Pathogenic	criteria provided, single submitter
1065507	NM_014762.4(DHCR24):c.1218+1G>A	DHCR24	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065498	NM_001372.4(DNAH9):c.2984del (p.Arg995fs)	DNAH9	Pathogenic	criteria provided, multiple submitters, no conflicts
692043	NM_182925.5(FLT4):c.3121C>T (p.Arg1041Trp)	FLT4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7257	NM_005251.3(FOXC2):c.914_921del (p.Tyr305fs)	FOXC2	Pathogenic	criteria provided, multiple submitters, no conflicts
190462	NM_024572.4(GALNT14):c.1273C>T (p.Arg425Ter)	GALNT14	Pathogenic	criteria provided, single submitter
894	NM_000181.4(GUSB):c.1144C>T (p.Arg382Cys)	GUSB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
908	NM_000181.4(GUSB):c.1069C>T (p.Arg357Ter)	GUSB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
439112	NM_000517.6(HBA2):c.179G>A (p.Gly60Asp)	HBA2	Pathogenic	criteria provided, multiple submitters, no conflicts
12604	NM_005343.4(HRAS):c.38G>A (p.Gly13Asp)	HRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
12612	NM_005343.4(HRAS):c.35G>A (p.Gly12Asp)	HRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
35554	NM_005343.4(HRAS):c.37G>C (p.Gly13Arg)	HRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065463	NM_001142864.4(PIEZO1):c.1792G>A (p.Val598Met)	HSALR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1252051	NM_153209.4(KIF19):c.788G>A (p.Arg263His)	KIF19	Pathogenic	no assertion criteria provided
373089	NM_006767.4(LZTR1):c.1234C>T (p.Arg412Cys)	LZTR1	Pathogenic	reviewed by expert panel
817718	NM_001127392.3(MYRF):c.789dup (p.Ser264fs)	MYRF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190457	NM_001164508.2(NEB):c.21076C>T (p.Arg7026Ter)	NEB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
218331	NM_000434.4(NEU1):c.353-2A>G	NEU1	Pathogenic	no assertion criteria provided
218332	NM_000434.4(NEU1):c.1170C>G (p.Tyr390Ter)	NEU1	Pathogenic	no assertion criteria provided
1065474	NM_022455.5(NSD1):c.3364dup (p.Ile1122fs)	NSD1	Pathogenic	criteria provided, single submitter
55806	NM_001142864.4(PIEZO1):c.7367G>A (p.Arg2456His)	PIEZO1	Pathogenic	criteria provided, multiple submitters, no conflicts
13330	NM_002834.5(PTPN11):c.182A>G (p.Asp61Gly)	PTPN11	Pathogenic	criteria provided, multiple submitters, no conflicts
13335	NM_002834.5(PTPN11):c.854T>C (p.Phe285Ser)	PTPN11	Pathogenic	criteria provided, multiple submitters, no conflicts
265307	NM_002834.5(PTPN11):c.1520C>A (p.Thr507Lys)	PTPN11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065464	NM_006912.6(RIT1):c.280G>T (p.Glu94Ter)	RIT1	Pathogenic	criteria provided, single submitter
181522	NM_006912.6(RIT1):c.246T>G (p.Phe82Leu)	RIT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
181528	NM_007373.4(SHOC2):c.519G>A (p.Met173Ile)	SHOC2	Pathogenic	reviewed by expert panel
190452	NM_000079.4(CHRNA1):c.687C>T (p.Arg229=)	CHRNA1	Likely pathogenic	criteria provided, single submitter
190458	NM_000308.4(CTSA):c.595del (p.Leu199fs)	CTSA	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 86 · 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
THSD1	Definitive	Autosomal recessive	non-immune hydrops fetalis	8
EHBP1L1	Strong	Autosomal recessive	non-immune hydrops fetalis

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
THSD1	Orphanet:231160	Familial cerebral saccular aneurysm
THSD1	Orphanet:363999	Non-immune hydrops fetalis
RIT1	Orphanet:648	Noonan syndrome
ARID1A	Orphanet:1465	Coffin-Siris syndrome
MYRF	Orphanet:647811	Cardiac-urogenital syndrome
ACTA1	Orphanet:171430	Severe congenital nemaline myopathy
ACTA1	Orphanet:171433	Intermediate nemaline myopathy
ACTA1	Orphanet:171436	Typical nemaline myopathy
ACTA1	Orphanet:171439	Childhood-onset nemaline myopathy
ACTA1	Orphanet:2020	Congenital fiber-type disproportion myopathy
ACTA1	Orphanet:447977	Progressive scapulohumeroperoneal distal myopathy
ACTA1	Orphanet:97240	Zebra body myopathy
ACTA1	Orphanet:97244	Rigid spine syndrome
ACTA1	Orphanet:98904	Congenital myopathy with excess of thin filaments
NSD1	Orphanet:1627	Deletion 5q35 syndrome
NSD1	Orphanet:228415	5q35 microduplication syndrome
NSD1	Orphanet:3447	Weaver syndrome
NSD1	Orphanet:821	Sotos syndrome
SHOC2	Orphanet:2701	Noonan syndrome-like disorder with loose anagen hair
SUZ12	Orphanet:213711	Endometrial stromal sarcoma
SUZ12	Orphanet:3447	Weaver syndrome
SUZ12	Orphanet:659463	Imagawa-Matsumoto syndrome
CHRNA1	Orphanet:33108	Lethal multiple pterygium syndrome
CHRNA1	Orphanet:98913	Postsynaptic congenital myasthenic syndrome
VPS13D	Orphanet:95434	Autosomal recessive cerebellar ataxia-movement disorder syndrome
DHCR24	Orphanet:35107	Desmosterolosis
PIEZO1	Orphanet:3202	Dehydrated hereditary stomatocytosis
PIEZO1	Orphanet:568062	PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis
ANKS3	Orphanet:101063	Situs inversus totalis
DNAH9	Orphanet:101063	Situs inversus totalis
DNAH9	Orphanet:157769	Situs ambiguus
DNAH9	Orphanet:244	Primary ciliary dyskinesia
EPHB4	Orphanet:1053	Vein of Galen malformation
EPHB4	Orphanet:568065	EPHB4-related lymphatic-related hydrops fetalis
EPHB4	Orphanet:693912	EPHB4-related capillary malformation-arteriovenous malformation
EPHB4	Orphanet:90186	Meige disease
FLT4	Orphanet:3303	Tetralogy of Fallot
FLT4	Orphanet:79452	Milroy disease
FOXC2	Orphanet:33001	Lymphedema-distichiasis syndrome
FZD6	Orphanet:280654	Autosomal recessive nail dysplasia
GUSB	Orphanet:584	Mucopolysaccharidosis type 7
HBA2	Orphanet:163596	Hemoglobin Bart’s fetalis syndrome
HBA2	Orphanet:247511	Autosomal dominant secondary polycythemia
HBA2	Orphanet:330041	Hemoglobin M disease
HBA2	Orphanet:707789	Unstable alpha globin chain variant disease
HBA2	Orphanet:715143	Heterozygous beta-thalassemia intermedia with supernumerary alpha-globin gene
HBA2	Orphanet:715154	Low oxygen affinity alpha chain hemoglobin disease
HBA2	Orphanet:93616	Hemoglobin H disease
HBA2	Orphanet:98791	Alpha-thalassemia-intellectual disability syndrome linked to chromosome 16
HRAS	Orphanet:146	Differentiated thyroid carcinoma

Cohort genes → proteins

43 cohort genes, 42 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	43

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
THSD1	HGNC:17754	ENSG00000136114	Q9NS62	Thrombospondin type-1 domain-containing protein 1	gencc,clinvar
EHBP1L1	HGNC:30682	ENSG00000173442	Q8N3D4	EH domain-binding protein 1-like protein 1	gencc,clinvar
RIT1	HGNC:10023	ENSG00000143622	Q92963	GTP-binding protein Rit1	clinvar
ROCK2	HGNC:10252	ENSG00000134318	O75116	Rho-associated protein kinase 2	clinvar
ARID1A	HGNC:11110	ENSG00000117713	O14497	AT-rich interactive domain-containing protein 1A	clinvar
MYRF	HGNC:1181	ENSG00000124920	Q9Y2G1	Myelin regulatory factor	clinvar
UBN1	HGNC:12506	ENSG00000118900	Q9NPG3	Ubinuclein-1	clinvar
ACTA1	HGNC:129	ENSG00000143632	P68133	Actin, alpha skeletal muscle	clinvar
NSD1	HGNC:14234	ENSG00000165671	Q96L73	Histone-lysine N-methyltransferase, H3 lysine-36 specific	clinvar
SHOC2	HGNC:15454	ENSG00000108061	Q9UQ13	Leucine-rich repeat protein SHOC-2	clinvar
MOCS3	HGNC:15765	ENSG00000124217	O95396	Adenylyltransferase and sulfurtransferase MOCS3	clinvar
SUZ12	HGNC:17101	ENSG00000178691	Q15022	Polycomb protein SUZ12	clinvar
PRPF19	HGNC:17896	ENSG00000110107	Q9UMS4	Pre-mRNA-processing factor 19	clinvar
FCRL4	HGNC:18507	ENSG00000163518	Q96PJ5	Fc receptor-like protein 4	clinvar
SERPINA11	HGNC:19193	ENSG00000186910	Q86U17	Serpin A11	clinvar
CHRNA1	HGNC:1955	ENSG00000138435	P02708	Acetylcholine receptor subunit alpha	clinvar
GALNT14	HGNC:22946	ENSG00000158089	Q96FL9	Polypeptide N-acetylgalactosaminyltransferase 14	clinvar
VPS13D	HGNC:23595	ENSG00000048707	Q5THJ4	Intermembrane lipid transfer protein VPS13D	clinvar
KIF19	HGNC:26735	ENSG00000196169	Q2TAC6	Kinesin-like protein KIF19	clinvar
SVOPL	HGNC:27034	ENSG00000157703	Q8N434	Putative transporter SVOPL	clinvar
DHCR24	HGNC:2859	ENSG00000116133	Q15392	Delta(24)-sterol reductase	clinvar
PIEZO1	HGNC:28993	ENSG00000103335	Q92508	Piezo-type mechanosensitive ion channel component 1	clinvar
ANKS3	HGNC:29422	ENSG00000168096	Q6ZW76	Ankyrin repeat and SAM domain-containing protein 3	clinvar
DNAH14	HGNC:2945	ENSG00000185842	Q0VDD8	Dynein axonemal heavy chain 14	clinvar
DNAH9	HGNC:2953	ENSG00000007174	Q9NYC9	Dynein axonemal heavy chain 9	clinvar
C1orf105	HGNC:29591	ENSG00000180999	O95561	Uncharacterized protein C1orf105	clinvar
MYBPHL	HGNC:30434	ENSG00000221986	A2RUH7	Myosin-binding protein H-like	clinvar
EPHB4	HGNC:3395	ENSG00000196411	P54760	Ephrin type-B receptor 4	clinvar
FEN1	HGNC:3650	ENSG00000168496	P39748	Flap endonuclease 1	clinvar
FLT4	HGNC:3767	ENSG00000037280	P35916	Vascular endothelial growth factor receptor 3	clinvar
FOXC2	HGNC:3801	ENSG00000176692	Q99958	Forkhead box protein C2	clinvar
FZD6	HGNC:4044	ENSG00000164930	O60353	Frizzled-6	clinvar
GUSB	HGNC:4696	ENSG00000169919	P08236	Beta-glucuronidase	clinvar
HBA2	HGNC:4824	ENSG00000188536	P69905	Hemoglobin subunit alpha	clinvar
HRAS	HGNC:5173	ENSG00000174775	P01112	GTPase HRas	clinvar
HSALR1	HGNC:56095	ENSG00000224888		HSP90AB1 associated lncRNA 1	clinvar
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar
LZTR1	HGNC:6742	ENSG00000099949	Q8N653	Leucine-zipper-like transcriptional regulator 1	clinvar
MYOM1	HGNC:7613	ENSG00000101605	P52179	Myomesin-1	clinvar
NEB	HGNC:7720	ENSG00000183091	P20929	Nebulin	clinvar
NEU1	HGNC:7758	ENSG00000204386	Q99519	Sialidase-1	clinvar
CTSA	HGNC:9251	ENSG00000064601	P10619	Lysosomal protective protein	clinvar
PTPN11	HGNC:9644	ENSG00000179295	Q06124	Tyrosine-protein phosphatase non-receptor type 11	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
THSD1	Thrombospondin type-1 domain-containing protein 1	Is a positive regulator of nascent focal adhesion assembly, involved in the modulation of endothelial cell attachment to the extracellular matrix.
EHBP1L1	EH domain-binding protein 1-like protein 1	May act as Rab effector protein and play a role in vesicle trafficking.
RIT1	GTP-binding protein Rit1	Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation.
ROCK2	Rho-associated protein kinase 2	Protein kinase which is a key regulator of actin cytoskeleton and cell polarity.
ARID1A	AT-rich interactive domain-containing protein 1A	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
MYRF	Myelin regulatory factor	Constitutes a precursor of the transcription factor.
UBN1	Ubinuclein-1	Acts as a novel regulator of senescence.
ACTA1	Actin, alpha skeletal muscle	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
NSD1	Histone-lysine N-methyltransferase, H3 lysine-36 specific	Histone methyltransferase that dimethylates Lys-36 of histone H3 (H3K36me2).
SHOC2	Leucine-rich repeat protein SHOC-2	Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates activation of the MAPK pathway.
MOCS3	Adenylyltransferase and sulfurtransferase MOCS3	Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln).
SUZ12	Polycomb protein SUZ12	Polycomb group (PcG) protein.
PRPF19	Pre-mRNA-processing factor 19	Ubiquitin-protein ligase which is a core component of several complexes mainly involved pre-mRNA splicing and DNA repair.
FCRL4	Fc receptor-like protein 4	May function as an inhibitor of the B-cell receptor signaling.
CHRNA1	Acetylcholine receptor subunit alpha	Upon acetylcholine binding, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
GALNT14	Polypeptide N-acetylgalactosaminyltransferase 14	Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor.
VPS13D	Intermembrane lipid transfer protein VPS13D	Mediates the transfer of lipids between membranes at organelle contact sites.
KIF19	Kinesin-like protein KIF19	Plus end-directed microtubule-dependent motor protein that regulates the length of motile cilia by mediating depolymerization of microtubules at ciliary tips.
DHCR24	Delta(24)-sterol reductase	Catalyzes the reduction of the delta-24 double bond of sterol intermediates during cholesterol biosynthesis.
PIEZO1	Piezo-type mechanosensitive ion channel component 1	Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain.
ANKS3	Ankyrin repeat and SAM domain-containing protein 3	May be involved in vasopressin signaling in the kidney.
DNAH14	Dynein axonemal heavy chain 14	Force generating protein of respiratory cilia.
DNAH9	Dynein axonemal heavy chain 9	Force generating protein required for cilia beating in respiratory epithelia.
MYBPHL	Myosin-binding protein H-like	Myosin-binding protein which plays a role in cardiac function.
EPHB4	Ephrin type-B receptor 4	Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.
FEN1	Flap endonuclease 1	Structure-specific nuclease with 5’-flap endonuclease and 5’-3’ exonuclease activities involved in DNA replication and repair.
FLT4	Vascular endothelial growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic developm…
FOXC2	Forkhead box protein C2	Transcriptional activator.
FZD6	Frizzled-6	Receptor for Wnt proteins.
GUSB	Beta-glucuronidase	Plays an important role in the degradation of dermatan and keratan sulfates.
HBA2	Hemoglobin subunit alpha	Involved in oxygen transport from the lung to the various peripheral tissues.
HRAS	GTPase HRas	Involved in the activation of Ras protein signal transduction.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
LZTR1	Leucine-zipper-like transcriptional regulator 1	Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates ubiquitination of Ras (K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS).
MYOM1	Myomesin-1	Major component of the vertebrate myofibrillar M band.
NEB	Nebulin	This giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils.
NEU1	Sialidase-1	Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids.
CTSA	Lysosomal protective protein	Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity.
PTPN11	Tyrosine-protein phosphatase non-receptor type 11	Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus.

Protein-family classification

Druggable: 18 · Difficult: 7 · Unknown: 18 · Druggable fraction: 0.42

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	4	2.7×	0.316
Enzyme (other)	7	1.9×	0.316
Kinase	3	1.9×	0.673
Phosphatase	1	1.9×	0.854
Transporter	1	1.8×	0.854
Transcription factor	5	1.0×	0.899
Protease	1	0.8×	0.899
Scaffold/PPI	2	0.8×	0.899
GPCR	1	0.6×	0.934
Other/Unknown	18	0.8×	0.977

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
THSD1	Other/Unknown	no		TSP1_rpt, TSP1_rpt_sf, THSD1
EHBP1L1	Other/Unknown	no		CH_dom, NT-C2, bMERB_dom
RIT1	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
ROCK2	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, PH_domain
ARID1A	Other/Unknown	no		ARID_dom, ARM-like, ARM-type_fold
MYRF	Transcription factor	no		p53-like_TF_DNA-bd_sf, NDT80_DNA-bd_dom, MYRF_C2
UBN1	Other/Unknown	no		HRD, UBN_middle_dom
ACTA1	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
NSD1	Transcription factor	no	2.1.1.357	PWWP_dom, SET_dom, Znf_PHD
SHOC2	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRR_dom_sf
MOCS3	Enzyme (other)	yes	2.7.7.80	ThiF_NAD_FAD-bd, Rhodanese-like_dom, MOCS3/Uba4
SUZ12	Transcription factor	no		Polycomb_protein_VEFS-Box, Znf_SUZ12
PRPF19	Transcription factor	no		WD40_rpt, Ubox_domain, Znf_RING/FYVE/PHD
FCRL4	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
SERPINA11	Other/Unknown	no		Serpin_fam, Serpin_dom, Serpin_sf
CHRNA1	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
GALNT14	Enzyme (other)	yes	2.4.1.41	Ricin_B_lectin, Glyco_trans_2-like, Nucleotide-diphossugar_trans
VPS13D	Other/Unknown	no		UBA-like_sf, VPS13_VAB, UBA
KIF19	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
SVOPL	Transporter	yes		MFS_sugar_transport-like, MFS, MFS_dom
DHCR24	Enzyme (other)	yes	1.3.1.72	Oxid_FAD_bind_N, FAD-bd_PCMH, FAD-bd_PCMH_sub2
PIEZO1	Other/Unknown	no		Piezo, Piezo_cap_dom, Piezo_TM25-28
ANKS3	Scaffold/PPI	no		SAM, Ankyrin_rpt, SAM/pointed_sf
DNAH14	Other/Unknown	no		Dhc_D4, Dynein_HC_stalk, DHC
DNAH9	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
C1orf105	Other/Unknown	no		DUF4548
MYBPHL	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
EPHB4	Kinase	yes	2.7.10.1	Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom
FEN1	Enzyme (other)	yes	3.1.99.B1	XPG/Rad2, XPG_DNA_repair_N, XPG-I_dom
FLT4	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
FOXC2	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
FZD6	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM
GUSB	Antibody/Immunoglobulin	yes	3.2.1.31	Glyco_hydro_2, Ig-like_GH2, Glyco_hydro_2_cat
HBA2	Other/Unknown	no		Globin, Hemoglobin_a-typ, Hemoglobin_pi
HRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
HSALR1	Other/Unknown	no
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
LZTR1	Other/Unknown	no		BTB/POZ_dom, Kelch_1, SKP1/BTB/POZ_sf
MYOM1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
NEB	Scaffold/PPI	no		Nebulin_repeat, SH3_domain, Nebulin-like
NEU1	Enzyme (other)	yes	3.2.1.18	Sialidase, Sialidase_fam, Sialidase_sf
CTSA	Protease	yes	3.4.16.5	Peptidase_S10, Ser_caboxypep_ser_AS, AB_hydrolase_fold
PTPN11	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, SH2

Expression context

Cohort genes with no expression data: 0.

37 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)	43
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	6
gluteal muscle	4
calcaneal tendon	3
colonic epithelium	3
lower esophagus mucosa	3
male germ line stem cell (sensu Vertebrata) in testis	3
right adrenal gland	3
right adrenal gland cortex	3
ventricular zone	2
monocyte	2
bone marrow cell	2
secondary oocyte	2
tendon of biceps brachii	2
male germ cell	2
sperm	2
buccal mucosa cell	2
skin of abdomen	2
skin of leg	2
right uterine tube	2
oocyte	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
THSD1	138	broad	marker	ventricular zone, right lung, apex of heart
EHBP1L1	233	ubiquitous	marker	granulocyte, lower esophagus, lower esophagus muscularis layer
RIT1	268	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
ROCK2	290	ubiquitous	marker	calcaneal tendon, colonic epithelium, middle temporal gyrus
ARID1A	286	ubiquitous	marker	bone marrow cell, ventricular zone, embryo
MYRF	223	ubiquitous	marker	middle frontal gyrus, C1 segment of cervical spinal cord, inferior vagus X ganglion
UBN1	296	ubiquitous	marker	lower esophagus mucosa, tendon of biceps brachii, secondary oocyte
ACTA1	203	broad	marker	gluteal muscle, skeletal muscle tissue of biceps brachii, diaphragm
NSD1	235	ubiquitous	marker	sural nerve, colonic epithelium, calcaneal tendon
SHOC2	299	ubiquitous	marker	calcaneal tendon, sural nerve, bone marrow
MOCS3	188	ubiquitous	yes	sperm, male germ cell, male germ line stem cell (sensu Vertebrata) in testis
SUZ12	288	ubiquitous	marker	trabecular bone tissue, mucosa of paranasal sinus, buccal mucosa cell
PRPF19	286	ubiquitous	marker	pons, right frontal lobe, Brodmann (1909) area 9
FCRL4	49	tissue_specific	marker	buccal mucosa cell, epithelium of nasopharynx, male germ line stem cell (sensu Vertebrata) in testis
SERPINA11	50	tissue_specific	yes	right lobe of liver, liver, minor salivary gland
CHRNA1	149	broad	marker	gastrocnemius, gluteal muscle, muscle of leg
GALNT14	194	broad	marker	lower esophagus mucosa, adult mammalian kidney, nephron tubule
VPS13D	299	ubiquitous	marker	skin of leg, skin of abdomen, sural nerve
KIF19	159	broad	marker	right uterine tube, sural nerve, tibial nerve
SVOPL	135	tissue_specific	marker	secondary oocyte, oocyte, olfactory segment of nasal mucosa
DHCR24	281	ubiquitous	marker	adrenal tissue, right adrenal gland cortex, right adrenal gland
PIEZO1	142	ubiquitous	marker	muscle layer of sigmoid colon, lower esophagus mucosa, upper lobe of left lung
ANKS3	195	ubiquitous	yes	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex
DNAH14	172	ubiquitous	marker	left testis, right testis, adrenal tissue
DNAH9	184	broad	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
C1orf105	139	tissue_specific	marker	sperm, male germ cell, left testis
MYBPHL	123	tissue_specific	yes	right atrium auricular region, male germ line stem cell (sensu Vertebrata) in testis, Ammon’s horn
EPHB4	282	ubiquitous	marker	olfactory bulb, type B pancreatic cell, body of uterus
FEN1	281	ubiquitous	marker	endometrium epithelium, oocyte, cervix squamous epithelium
FLT4	172	broad	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland

Protein interactions among cohort

Intra-cohort edges: 17.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRAS	14,509
HRAS	8,064
PTPN11	6,009
FEN1	4,897
PRPF19	4,658
SUZ12	4,349
ROCK2	4,121
GUSB	3,659
ARID1A	3,476
RIT1	3,298

Intra-cohort edges

A	B	Sources
CTSA	NEU1	string_interaction
DHCR24	HRAS	biogrid_interaction
DNAH9	THSD1	string_interaction
FCRL4	PTPN11	string_interaction
FEN1	MYRF	string_interaction
FLT4	FOXC2	string_interaction
HRAS	LZTR1	biogrid_interaction
HRAS	SHOC2	intact, string_interaction
KRAS	LZTR1	string_interaction
KRAS	SHOC2	intact, string_interaction
LZTR1	RIT1	biogrid_interaction, intact, string_interaction
LZTR1	SHOC2	string_interaction
MYBPHL	PRPF19	string_interaction
MYOM1	NEB	string_interaction
PRPF19	PTPN11	string_interaction
PTPN11	SHOC2	string_interaction
RIT1	SHOC2	string_interaction

Structural data

PDB: 29 · AlphaFold-only: 13 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
HBA2	P69905	356
HRAS	P01112	246
PTPN11	Q06124	115
SUZ12	Q15022	30
FEN1	P39748	28
PRPF19	Q9UMS4	23
EPHB4	P54760	23
ROCK2	O75116	21
CHRNA1	P02708	15
SHOC2	Q9UQ13	13
CTSA	P10619	12
MYOM1	P52179	9
ARID1A	O14497	7
PIEZO1	Q92508	6
FOXC2	Q99958	6
ACTA1	P68133	5
NSD1	Q96L73	4
RIT1	Q92963	3
LZTR1	Q8N653	3
NEB	P20929	3
MYRF	Q9Y2G1	2
ANKS3	Q6ZW76	2
FLT4	P35916	2
FZD6	O60353	2
GUSB	P08236	2
UBN1	Q9NPG3	1
MOCS3	O95396	1
DNAH9	Q9NYC9	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DHCR24	Q15392	92.40
GALNT14	Q96FL9	89.23
NEU1	Q99519	89.12
MYBPHL	A2RUH7	86.64
SVOPL	Q8N434	84.29
SERPINA11	Q86U17	83.27
FCRL4	Q96PJ5	78.56
KIF19	Q2TAC6	65.40
THSD1	Q9NS62	59.46
C1orf105	O95561	57.57
EHBP1L1	Q8N3D4	49.98
VPS13D	Q5THJ4
DNAH14	Q0VDD8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 286. Enrichment computed across 43 evidence-associated genes (29 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 29 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by RAS GAP mutants	2	262.5×	9e-04	HRAS, KRAS
Signaling by RAS GTPase mutants	2	262.5×	9e-04	HRAS, KRAS
Activated NTRK2 signals through FRS2 and FRS3	3	98.5×	9e-04	HRAS, KRAS, PTPN11
Signaling by FLT3 ITD and TKD mutants	3	78.8×	9e-04	HRAS, KRAS, PTPN11
Tie2 Signaling	3	62.2×	9e-04	HRAS, KRAS, PTPN11
FRS-mediated FGFR3 signaling	3	56.3×	9e-04	HRAS, KRAS, PTPN11
FRS-mediated FGFR4 signaling	3	51.4×	0.001	HRAS, KRAS, PTPN11
Defective NEU1 causes sialidosis	2	196.9×	0.001	NEU1, CTSA
FRS-mediated FGFR1 signaling	3	47.3×	0.001	HRAS, KRAS, PTPN11
FRS-mediated FGFR2 signaling	3	45.4×	0.001	HRAS, KRAS, PTPN11
Activation of RAS in B cells	2	157.5×	0.001	HRAS, KRAS
Downstream signal transduction	3	39.4×	0.001	HRAS, KRAS, PTPN11
FLT3 Signaling	3	35.8×	0.002	HRAS, KRAS, PTPN11
RAF activation	3	34.8×	0.002	SHOC2, HRAS, KRAS
RAS signaling downstream of NF1 loss-of-function variants	2	112.5×	0.002	HRAS, KRAS
Estrogen-stimulated signaling through PRKCZ	2	112.5×	0.002	HRAS, KRAS
SOS-mediated signalling	2	98.5×	0.003	HRAS, KRAS
EPHB-mediated forward signaling	3	27.5×	0.003	ROCK2, EPHB4, HRAS
Signaling by SCF-KIT	3	25.7×	0.003	HRAS, KRAS, PTPN11
Activated NTRK3 signals through RAS	2	87.5×	0.003	HRAS, KRAS
EGFR Transactivation by Gastrin	2	78.8×	0.003	HRAS, KRAS
SHC-related events triggered by IGF1R	2	78.8×	0.003	HRAS, KRAS
Activated NTRK2 signals through RAS	2	78.8×	0.003	HRAS, KRAS
MET activates RAS signaling	2	71.6×	0.004	HRAS, KRAS
Signaling by FGFR4 in disease	2	65.6×	0.004	HRAS, KRAS
Constitutive Signaling by Overexpressed ERBB2	2	65.6×	0.004	HRAS, KRAS
p38MAPK events	2	60.6×	0.005	HRAS, KRAS
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	2	60.6×	0.005	HRAS, KRAS
Signaling by PDGFRA extracellular domain mutants	2	60.6×	0.005	HRAS, KRAS
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases	2	56.3×	0.005	HRAS, KRAS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 37 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
Ras protein signal transduction	4	22.2×	0.012	RIT1, DHCR24, HRAS, KRAS
positive regulation of connective tissue growth factor production	1	455.5×	0.059	ROCK2
regulation of peptidyl-serine phosphorylation	1	455.5×	0.059	NSD1
response to mineralocorticoid	1	455.5×	0.059	KRAS
negative regulation of cortisol secretion	1	455.5×	0.059	PTPN11
negative regulation of growth hormone secretion	1	455.5×	0.059	PTPN11
axonemal microtubule depolymerization	1	455.5×	0.059	KIF19
plus-end specific microtubule depolymerization	1	455.5×	0.059	KIF19
cellular response to growth hormone stimulus	1	455.5×	0.059	SHOC2
regulation of RNA polymerase II regulatory region sequence-specific DNA binding	1	455.5×	0.059	NSD1
lymphangiogenesis	2	65.1×	0.059	FLT4, FOXC2
regulation of long-term neuronal synaptic plasticity	2	53.6×	0.059	HRAS, KRAS
cilium movement involved in cell motility	2	36.4×	0.059	DNAH14, DNAH9
blood vessel diameter maintenance	2	33.7×	0.059	ROCK2, FOXC2
cardiac muscle cell proliferation	2	31.4×	0.059	FOXC2, KRAS
apoptotic process involved in outflow tract morphogenesis	1	227.7×	0.064	FOXC2
growth plate cartilage morphogenesis	1	227.7×	0.064	GUSB
microvillus organization	1	227.7×	0.064	PTPN11
paraxial mesodermal cell fate commitment	1	227.7×	0.064	FOXC2
intestinal epithelial cell migration	1	227.7×	0.064	PTPN11
regulation of angiotensin-activated signaling pathway	1	227.7×	0.064	ROCK2
negative regulation of protein localization to lysosome	1	227.7×	0.064	ROCK2
negative regulation of apoptotic process involved in outflow tract morphogenesis	1	227.7×	0.064	FOXC2
vascular endothelial growth factor receptor signaling pathway	2	26.0×	0.064	FLT4, FOXC2
homeostasis of number of cells within a tissue	2	24.0×	0.064	KRAS, PTPN11
response to hormone	2	23.4×	0.064	DHCR24, FOXC2
oligodendrocyte differentiation	2	22.8×	0.064	MYRF, SUZ12
DNA damage checkpoint signaling	2	21.2×	0.064	PRPF19, PTPN11
cerebellar cortex formation	1	151.8×	0.065	PTPN11
forebrain astrocyte development	1	151.8×	0.065	KRAS

Therapeutics

Drug target analysis

Approved (phase 4): 12 · Phase ≥3: 12 · Phased (≥1): 12 · Undrugged: 31

Druggability breadth: 21 of 43 evidence-associated genes (49%) 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
ROCK2	MOMELOTINIB
NSD1	VENETOCLAX
SUZ12	TAZEMETOSTAT
CHRNA1	VARENICLINE
DHCR24	GILTERITINIB
EPHB4	PONATINIB
FLT4	FEDRATINIB
GUSB	PRASTERONE
HRAS	LONAFARNIB
KRAS	VEMURAFENIB
CTSA	ISOFLUROPHATE
PTPN11	ESTRAMUSTINE PHOSPHATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FLT4	72	4
ROCK2	52	4
EPHB4	46	4
CHRNA1	12	4
KRAS	11	4
PTPN11	8	4
NSD1	7	4
HRAS	4	4
SUZ12	2	4
GUSB	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	ROCK2
FEDRATINIB	4	EPHB4, FLT4, ROCK2
RUXOLITINIB	4	ROCK2
PALBOCICLIB	4	ROCK2
BELUMOSUDIL	4	ROCK2
TOFACITINIB CITRATE	4	ROCK2
BARICITINIB	4	ROCK2
TOFACITINIB	4	ROCK2
CAPIVASERTIB	4	ROCK2
CERITINIB	4	ROCK2
VANDETANIB	4	EPHB4, FLT4, ROCK2
BOSUTINIB	4	EPHB4, ROCK2
UPADACITINIB	4	ROCK2
NETARSUDIL	4	ROCK2
SUNITINIB	4	EPHB4, FLT4, ROCK2
CRIZOTINIB	4	EPHB4, ROCK2
MIDOSTAURIN	4	FLT4, ROCK2
VENETOCLAX	4	NSD1
PRIMAQUINE	4	NSD1
CHLOROQUINE PHOSPHATE	4	NSD1
TAZEMETOSTAT	4	SUZ12
VARENICLINE	4	CHRNA1
NICOTINE	4	CHRNA1
TROPISETRON	4	CHRNA1
BUPROPION	4	CHRNA1
MECAMYLAMINE	4	CHRNA1
GILTERITINIB	4	DHCR24
PONATINIB	4	EPHB4
TIVOZANIB	4	EPHB4, FLT4
SORAFENIB	4	EPHB4, FLT4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 13.

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

Symbol	Assays	Type breakdown
KRAS	861	Binding:829, Functional:32
ROCK2	788	Binding:783, Functional:3, ADMET:1, Toxicity:1
FLT4	717	Binding:683, Functional:32, ADMET:2
PTPN11	588	Binding:585, Functional:2, ADMET:1
EPHB4	437	Binding:437
CHRNA1	157	Binding:107, Functional:47, ADMET:2, Toxicity:1
NSD1	90	Binding:90
HBA2	59	Binding:46, Functional:13
SUZ12	51	Binding:51
HRAS	48	Binding:45, Functional:3
GUSB	41	Binding:38, ADMET:3
NEU1	27	Binding:27
CTSA	19	Binding:13, ADMET:6
PIEZO1	17	Binding:17
FEN1	15	Binding:12, Functional:3
DHCR24	10	Binding:10
PRPF19	7	Binding:7
ARID1A	6	Binding:6
MOCS3	2	Binding:2
FOXC2	2	Binding:2
GALNT14	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NSD1	2.1.1.357, 2.1.1.362	[histone H3]-lysine36 N-dimethyltransferase, [histone H4]-N-methyl-L-lysine20 N-methyltransferase
MOCS3	2.7.7.80, 2.8.1.11	molybdopterin-synthase adenylyltransferase, molybdopterin synthase sulfurtransferase
GALNT14	2.4.1.41	polypeptide N-acetylgalactosaminyltransferase
DHCR24	1.3.1.72	DELTA24-sterol reductase
EPHB4	2.7.10.1	receptor protein-tyrosine kinase
FEN1	3.1.99.B1
FLT4	2.7.10.1	receptor protein-tyrosine kinase
GUSB	3.2.1.31	beta-glucuronidase
HRAS	3.6.5.2	small monomeric GTPase
KRAS	3.6.5.2	small monomeric GTPase
NEU1	3.2.1.18	exo-alpha-sialidase
CTSA	3.4.16.5	carboxypeptidase C
PTPN11	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
ROCK2	788
CHRNA1	157
EPHB4	437
FLT4	717
KRAS	861
PTPN11	588

Pharmacogenomics

Cohort genes with a PharmGKB record: 42; 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)
MOMELOTINIB	4	ROCK2
FEDRATINIB	4	EPHB4, FLT4, ROCK2
RUXOLITINIB	4	ROCK2
PALBOCICLIB	4	ROCK2
BELUMOSUDIL	4	ROCK2
TOFACITINIB CITRATE	4	ROCK2
BARICITINIB	4	ROCK2
TOFACITINIB	4	ROCK2
CAPIVASERTIB	4	ROCK2
CERITINIB	4	ROCK2
VANDETANIB	4	EPHB4, FLT4, ROCK2
BOSUTINIB	4	EPHB4, ROCK2
UPADACITINIB	4	ROCK2
NETARSUDIL	4	ROCK2
SUNITINIB	4	EPHB4, FLT4, ROCK2
CRIZOTINIB	4	EPHB4, ROCK2
MIDOSTAURIN	4	FLT4, ROCK2
VENETOCLAX	4	NSD1
PRIMAQUINE	4	NSD1
CHLOROQUINE PHOSPHATE	4	NSD1
TAZEMETOSTAT	4	SUZ12
VARENICLINE	4	CHRNA1
NICOTINE	4	CHRNA1
TROPISETRON	4	CHRNA1
BUPROPION	4	CHRNA1
MECAMYLAMINE	4	CHRNA1
GILTERITINIB	4	DHCR24
PONATINIB	4	EPHB4
TIVOZANIB	4	EPHB4, FLT4
SORAFENIB	4	EPHB4, FLT4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	12	ROCK2, NSD1, SUZ12, CHRNA1, DHCR24, EPHB4, FLT4, GUSB, HRAS, KRAS (+2 more)
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	4	MOCS3, FEN1, FZD6, MYOM1
D	Druggable family + AlphaFold only, no drug	5	FCRL4, GALNT14, SVOPL, MYBPHL, NEU1
E	Difficult family or no structure, no drug	22	THSD1, EHBP1L1, RIT1, ARID1A, MYRF, UBN1, ACTA1, SHOC2, PRPF19, SERPINA11 (+12 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PRPF19	7	PTPN11
FCRL4	0	PTPN11
FOXC2	2	FLT4
NEU1	27	CTSA
THSD1	0	—
EHBP1L1	0	—
RIT1	0	—
ARID1A	6	—
MYRF	0	—
UBN1	0	—
ACTA1	0	—
SHOC2	0	—
MOCS3	2	—
SERPINA11	0	—
GALNT14	1	—
VPS13D	0	—
KIF19	0	—
SVOPL	0	—
PIEZO1	17	—
ANKS3	0	—
DNAH14	0	—
DNAH9	0	—
C1orf105	0	—
MYBPHL	0	—
FEN1	15	—
FZD6	0	—
HBA2	59	—
HSALR1	0	—
LZTR1	0	—
MYOM1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05528796	Not specified	ENROLLING_BY_INVITATION	Uncovering the Etiologies of Non-immune Hydrops Fetalis
NCT04308603	Not specified	COMPLETED	Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing