Hemorrhoid

Summary

Hemorrhoid (MONDO:0004872) is a disease with 75 cohort genes (132 GWAS associations across 52 studies) and 159 clinical trials. The dominant Reactome pathway is Formation of the ureteric bud (3 cohort genes). Top therapeutic interventions include bupivacaine, lidocaine, and diosmin.

At a glance

• Cohort genes: 75
• GWAS associations: 132
• Clinical trials: 159

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hemorrhoid
Mondo ID	MONDO:0004872
EFO	EFO:0009552
MeSH	D006484
DOID	DOID:9746
ICD-11	1352501137
NCIT	C26792
SNOMED CT	70153002
UMLS	C0019112
MedGen	5507
Is cancer (heuristic)	no

Also known as: Haemorrhoids · hemorrhoid · Hemorrhoids

Data availability: 132 GWAS associations (52 studies).

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › vein disorder › varicose disease › pelvic varices › hemorrhoid

Related subtypes (2): varicocele, vulval varices

Subtypes (2): perianal hematoma, internal hemorrhoid

Genetics & variants

GWAS landscape

132 GWAS associations across 52 studies. Top hits map to 38 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs11176001	2e-46	HMGA2 - MIR6074	A	0.92
rs676996	5e-43	ABO	T	0.94
rs1838392	5e-39	XKR9	T	1.05
rs11585073	4e-33	LINC02811	A	1.06
rs17293632	7e-32	SMAD3	T	1.06
rs722587	2e-31	GMDS	A	0.95
rs145163454	6e-28	ATP1B1	T	0.87
rs1333047	8e-28	CDKN2B-AS1	A	1.04
rs9847710	1e-23	SFMBT1	T	1.04
rs4556017	1e-22	MUC12	T	1.06
chr9:133274084	2e-18		T	0.08
rs11770437	3e-18	TMEM270 - ELN	?	0.96
rs900400	5e-18	LINC00880	?	0.97
rs7778418	6e-18	FAM185A	?	1.04
rs847148	1e-17	HOXD11	?	0.96
rs7994724	2e-17	RNASEH2B-AS1, DLEU1	?	1.04
rs2912053	2e-17	AGPAT5 - XKR5	?	1.04
chr9:133270637	8e-17		A	0.06
rs4910165	4e-16	IRAG1	?	1.03
rs8176746	2e-15	ABO	G	0.08
rs62368263	6e-15	HMGB1P47 - RNA5SP182	?	0.96
rs7594056	7e-15	GDF7	?	0.97
rs6792493	1e-14	PLCXD2, PHLDB2	?	1.03
chr12:66015587	1e-14		A	0.1
rs2421206	2e-14	SPC24	?	1.03
chr12:65999976	3e-14		C	0.08
rs2597301	6e-14	RNU6-281P - FOXP1	?	1.03
rs4345978	1e-13	CLMP	?	0.97
rs7183672	1e-13	LINC00924	?	1.03
rs2218793	1e-13	AMPD3	?	1.03

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90014033	Zheng T	2021	218,920	725,213	Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease.
GCST90476015	Verma A	2024	55,499	325,007	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473861	UK Biobank Whole-Genome Sequencing Consortium	2025	46,852	411,588	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667824	UK Biobank Whole-Genome Sequencing Consortium	2025	46,852	411,588	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90473614	UK Biobank Whole-Genome Sequencing Consortium	2025	28,829	429,611	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667888	UK Biobank Whole-Genome Sequencing Consortium	2025	28,829	429,611	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90080074	Backman JD	2021	27,106	360,824	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084060	Backman JD	2021	27,106	360,824	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90436180	Zhou W	2018	23,896	369,592	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90478043	Verma A	2024	17,547	85,099	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	1
Tier 3: regulatory	2
Tier 4: intronic/intergenic	45

MAF distribution

Bucket	Variants
common (>=0.05)	45
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	4

Functional consequences

Consequence	Count
intron_variant	32
intergenic_variant	6
unknown	4
non_coding_transcript_exon_variant	3
regulatory_region_variant	2
missense_variant	2
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs11176001	12	66015587	C>A	0.129	intergenic_variant	HMGA2 - MIR6074	2e-46	Tier 4: intronic/intergenic
rs676996	9	133270647	G>A,T	0.341	intron_variant	ABO	5e-43	Tier 4: intronic/intergenic
rs1838392	8	70770348	T>A,G	0.39	intron_variant	XKR9	5e-39	Tier 4: intronic/intergenic
rs11585073	1	39809417	A>T	0.245	non_coding_transcript_exon_variant	LINC02811	4e-33	Tier 4: intronic/intergenic
rs17293632	15	67150258	C>A,T	0.237	intron_variant	SMAD3	7e-32	Tier 4: intronic/intergenic
rs722587	6	1775480	A>T	0.283	intron_variant	GMDS	2e-31	Tier 4: intronic/intergenic
rs145163454	1	169121510	T>A,C	0.025	intron_variant	ATP1B1	6e-28	Tier 4: intronic/intergenic
rs1333047	9	22124505	A>C,G,T	0.5	intergenic_variant	CDKN2B-AS1	8e-28	Tier 4: intronic/intergenic
rs9847710	3	53028645	T>A,C	0.415	intron_variant	SFMBT1	1e-23	Tier 4: intronic/intergenic
rs4556017	7	100989509	C>T	0.144	intron_variant	MUC12	1e-22	Tier 4: intronic/intergenic
chr9:133274084							2e-18	Tier 4: intronic/intergenic
rs11770437	7	73905479	C>A,T	0.359	intergenic_variant	TMEM270 - ELN	3e-18	Tier 4: intronic/intergenic
rs900400	3	157080986	T>C,G	0.412	intron_variant	LINC00880	5e-18	Tier 4: intronic/intergenic
rs7778418	7	102789257	T>A,C	0.341	intron_variant	FAM185A	6e-18	Tier 4: intronic/intergenic
rs847148	2	176105728	A>C,T	0.32	regulatory_region_variant	HOXD11	1e-17	Tier 3: regulatory
rs7994724	13	50871424	A>C,G,T	0.371	intergenic_variant	RNASEH2B-AS1, DLEU1	2e-17	Tier 4: intronic/intergenic
rs2912053	8	6788272	G>C	0.398	non_coding_transcript_exon_variant	AGPAT5 - XKR5	2e-17	Tier 4: intronic/intergenic
chr9:133270637							8e-17	Tier 4: intronic/intergenic
rs4910165	11	10652497	C>G	0.321	intron_variant	IRAG1	4e-16	Tier 4: intronic/intergenic
rs8176746	9	133255935	G>A,C,T	0.091	missense_variant	ABO	2e-15	Tier 1: coding
rs62368263	5	51430193	T>C	0.143	intron_variant	HMGB1P47 - RNA5SP182	6e-15	Tier 4: intronic/intergenic
rs7594056	2	20667984	A>C,G,T	0.314	intron_variant	GDF7	7e-15	Tier 4: intronic/intergenic
rs6792493	3	111758501	A>G	0.412	intron_variant	PLCXD2, PHLDB2	1e-14	Tier 4: intronic/intergenic
chr12:66015587							1e-14	Tier 4: intronic/intergenic
rs2421206	19	11151801	T>G	0.347	intron_variant	SPC24	2e-14	Tier 4: intronic/intergenic
chr12:65999976							3e-14	Tier 4: intronic/intergenic
rs2597301	3	70860343	C>G	0.321	intergenic_variant	RNU6-281P - FOXP1	6e-14	Tier 4: intronic/intergenic
rs4345978	11	123139043	G>T	0.247	intron_variant	CLMP	1e-13	Tier 4: intronic/intergenic
rs7183672	15	95557789	A>G	0.32	regulatory_region_variant	LINC00924	1e-13	Tier 3: regulatory
rs2218793	11	10359281	C>A,G,T	0.287	intron_variant	AMPD3	1e-13	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 75 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BMPR1B	Orphanet:2098	Acromesomelic dysplasia, Grebe type
BMPR1B	Orphanet:2639	Fibular aplasia-complex brachydactyly syndrome
BMPR1B	Orphanet:93384	Brachydactyly type C
BMPR1B	Orphanet:93388	Brachydactyly type A1
BMPR1B	Orphanet:93396	Brachydactyly type A2
TMPRSS4	Orphanet:363969	Autosomal recessive cerebral atrophy
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
ZBTB20	Orphanet:3042	Intellectual disability-cataracts-calcified pinnae-myopathy syndrome
SUGCT	Orphanet:35706	Glutaric acidemia type 3
BICD2	Orphanet:363454	BICD2-related autosomal dominant childhood-onset proximal spinal muscular atrophy
MAP3K20	Orphanet:2020	Congenital fiber-type disproportion myopathy
MAP3K20	Orphanet:488232	Split-foot malformation-mesoaxial polydactyly syndrome
CDKN2B	Orphanet:618	Familial melanoma
CDKN2B	Orphanet:652	Multiple endocrine neoplasia type 1
GREM1	Orphanet:157794	Hereditary mixed polyposis syndrome
COL5A2	Orphanet:287	Classical Ehlers-Danlos syndrome
TMEM270	Orphanet:904	Williams syndrome
CLMP	Orphanet:2301	Congenital short bowel syndrome
TET2	Orphanet:100019	Myelodysplastic neoplasm with increased blasts type 1
TET2	Orphanet:100020	Myelodysplastic neoplasm with increased blasts type 2
TET2	Orphanet:3318	Essential thrombocythemia
TET2	Orphanet:664729	EBV-induced lymphoproliferative disease due to TET2 deficiency
TET2	Orphanet:75564	Acquired idiopathic sideroblastic anemia
TET2	Orphanet:824	Primary myelofibrosis
TET2	Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features
TET2	Orphanet:98826	Myelodysplastic neoplasm with low blasts
TET2	Orphanet:98849	Systemic mastocytosis with associated hematologic neoplasm
TET2	Orphanet:98850	Aggressive systemic mastocytosis
KIAA0825	Orphanet:93334	Postaxial polydactyly type A
CHRDL1	Orphanet:91489	Isolated congenital megalocornea
EGFR	Orphanet:251576	Gliosarcoma

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BMP8B	HGNC:1075	ENSG00000116985	P34820	Bone morphogenetic protein 8B	gwas
BMPR1B	HGNC:1077	ENSG00000138696	O00238	Bone morphogenetic protein receptor type-1B	gwas
BTC	HGNC:1121	ENSG00000174808	P35070	Probetacellulin	gwas
SRPX	HGNC:11309	ENSG00000101955	P78539	Sushi repeat-containing protein SRPX	gwas
TCF21	HGNC:11632	ENSG00000118526	O43680	Transcription factor 21	gwas
THBS2	HGNC:11786	ENSG00000186340	P35442	Thrombospondin-2	gwas
TMPRSS4	HGNC:11878	ENSG00000137648	Q9NRS4	Transmembrane protease serine 4	gwas
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	gwas
ACOX3	HGNC:121	ENSG00000087008	O15254	Peroxisomal acyl-coenzyme A oxidase 3	gwas
UGDH	HGNC:12525	ENSG00000109814	O60701	UDP-glucose 6-dehydrogenase	gwas
ZBTB20	HGNC:13503	ENSG00000181722	Q9HC78	Zinc finger and BTB domain-containing protein 20	gwas
FBXL7	HGNC:13604	ENSG00000183580	Q9UJT9	F-box/LRR-repeat protein 7	gwas
HDAC7	HGNC:14067	ENSG00000061273	Q8WUI4	Histone deacetylase 7	gwas
HHIP	HGNC:14866	ENSG00000164161	Q96QV1	Hedgehog-interacting protein	gwas
RBM38	HGNC:15818	ENSG00000132819	Q9H0Z9	RNA-binding protein 38	gwas
SUGCT	HGNC:16001	ENSG00000175600	Q9HAC7	Succinyl-CoA:glutarate CoA-transferase	gwas
TRIM31	HGNC:16289	ENSG00000204616	Q9BZY9	E3 ubiquitin-protein ligase TRIM31	gwas
BICD2	HGNC:17208	ENSG00000185963	Q8TD16	Protein bicaudal D homolog 2	gwas
ACVR2A	HGNC:173	ENSG00000121989	P27037	Activin receptor type-2A	gwas
DLEU7	HGNC:17567	ENSG00000186047	Q6UYE1	Leukemia-associated protein 7	gwas
MTCH2	HGNC:17587	ENSG00000109919	Q9Y6C9	Mitochondrial carrier homolog 2	gwas
MAP3K20	HGNC:17797	ENSG00000091436	Q9NYL2	Mitogen-activated protein kinase kinase kinase 20	gwas
CDKN2B	HGNC:1788	ENSG00000147883	P42772	Cyclin-dependent kinase 4 inhibitor B	gwas
FGD5	HGNC:19117	ENSG00000154783	Q6ZNL6	FYVE, RhoGEF and PH domain-containing protein 5	gwas
ZNF404	HGNC:19417	ENSG00000176222	Q494X3	Zinc finger protein 404	gwas
GREM1	HGNC:2001	ENSG00000166923	O60565	Gremlin-1	gwas
SFMBT1	HGNC:20255	ENSG00000163935	Q9UHJ3	Scm-like with four MBT domains protein 1	gwas
XKR9	HGNC:20937	ENSG00000221947	Q5GH70	XK-related protein 9	gwas
DCBLD1	HGNC:21479	ENSG00000164465	Q8N8Z6	Discoidin, CUB and LCCL domain-containing protein 1	gwas
ANO1	HGNC:21625	ENSG00000131620	Q5XXA6	Anoctamin-1	gwas
COL5A2	HGNC:2210	ENSG00000204262	P05997	Collagen alpha-2(V) chain	gwas
FAM185A	HGNC:22412	ENSG00000222011	Q8N0U4	Protein FAM185A	gwas
TMEM270	HGNC:23018	ENSG00000175877	Q6UE05	Transmembrane protein 270	gwas
CCAR2	HGNC:23360	ENSG00000158941	Q8N163	Cell cycle and apoptosis regulator protein 2	gwas
CLMP	HGNC:24039	ENSG00000166250	Q9H6B4	CXADR-like membrane protein	gwas
TPPP	HGNC:24164	ENSG00000171368	O94811	Tubulin polymerization-promoting protein	gwas
CTBP2	HGNC:2495	ENSG00000175029	P56545	C-terminal-binding protein 2	gwas
EXOC2	HGNC:24968	ENSG00000112685	Q96KP1	Exocyst complex component 2	gwas
KIAA1217	HGNC:25428	ENSG00000120549	Q5T5P2	Sickle tail protein homolog	gwas
SRBD1	HGNC:25521	ENSG00000068784	Q8N5C6	S1 RNA-binding domain-containing protein 1	gwas
TET2	HGNC:25941	ENSG00000168769	Q6N021	Methylcytosine dioxygenase TET2	gwas
TTC27	HGNC:25986	ENSG00000018699	Q6P3X3	Tetratricopeptide repeat protein 27	gwas
PLCXD2	HGNC:26462	ENSG00000240891	Q0VAA5	PI-PLC X domain-containing protein 2	gwas
SPC24	HGNC:26913	ENSG00000161888	Q8NBT2	Kinetochore protein Spc24	gwas
PIAS1	HGNC:2752	ENSG00000033800	O75925	E3 SUMO-protein ligase PIAS1	gwas
KIAA0825	HGNC:28532	ENSG00000185261	Q8IV33	Uncharacterized protein KIAA0825	gwas
SLC44A3	HGNC:28689	ENSG00000143036	Q8N4M1	Choline transporter-like protein 3	gwas
EHBP1	HGNC:29144	ENSG00000115504	Q8NDI1	EH domain-binding protein 1	gwas
CHRDL1	HGNC:29861	ENSG00000101938	Q9BU40	Chordin-like protein 1	gwas
SND1	HGNC:30646	ENSG00000197157	Q7KZF4	Staphylococcal nuclease domain-containing protein 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BMP8B	Bone morphogenetic protein 8B	Induces cartilage and bone formation.
BMPR1B	Bone morphogenetic protein receptor type-1B	On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.
BTC	Probetacellulin	Growth factor that binds to EGFR, ERBB4 and other EGF receptor family members.
SRPX	Sushi repeat-containing protein SRPX	May be involved in phagocytosis during disk shedding, cell adhesion to cells other than the pigment epithelium or signal transduction.
TCF21	Transcription factor 21	Involved in epithelial-mesenchymal interactions in kidney and lung morphogenesis that include epithelial differentiation and branching morphogenesis.
THBS2	Thrombospondin-2	Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions.
TMPRSS4	Transmembrane protease serine 4	Plasma membrane-anchored serine protease that directly induces processing of pro-uPA/PLAU into the active form through proteolytic activity.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
ACOX3	Peroxisomal acyl-coenzyme A oxidase 3	Oxidizes the CoA-esters of 2-methyl-branched fatty acids.
UGDH	UDP-glucose 6-dehydrogenase	Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans.
ZBTB20	Zinc finger and BTB domain-containing protein 20	May be a transcription factor that may be involved in hematopoiesis, oncogenesis, and immune responses.
FBXL7	F-box/LRR-repeat protein 7	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex.
HDAC7	Histone deacetylase 7	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
HHIP	Hedgehog-interacting protein	Modulates hedgehog signaling in several cell types including brain and lung through direct interaction with members of the hedgehog family.
RBM38	RNA-binding protein 38	RNA-binding protein that specifically bind the 3’-UTR of CDKN1A transcripts, leading to maintain the stability of CDKN1A transcripts, thereby acting as a mediator of the p53/TP53 family to regulate CDKN1A.
SUGCT	Succinyl-CoA:glutarate CoA-transferase	Coenzyme A (CoA) transferase that reversibly catalyzes the transfer of a CoA moiety from a dicarboxyl-CoA to a dicarboxylate in a metabolite recycling process.
TRIM31	E3 ubiquitin-protein ligase TRIM31	E3 ubiquitin-protein ligase that acts as a regulator of antiviral immune response and inflammation by mediating ubiquitination of substrates.
BICD2	Protein bicaudal D homolog 2	Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin.
ACVR2A	Activin receptor type-2A	On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.
MTCH2	Mitochondrial carrier homolog 2	Protein insertase that mediates insertion of transmembrane proteins into the mitochondrial outer membrane.
MAP3K20	Mitogen-activated protein kinase kinase kinase 20	Stress-activated component of a protein kinase signal transduction cascade that promotes programmed cell death in response to various stress, such as ribosomal stress, osmotic shock and ionizing radiation.
CDKN2B	Cyclin-dependent kinase 4 inhibitor B	Interacts strongly with CDK4 and CDK6.
FGD5	FYVE, RhoGEF and PH domain-containing protein 5	Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP.
ZNF404	Zinc finger protein 404	May be involved in transcriptional regulation.
GREM1	Gremlin-1	Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as a BMP antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH feedback loop.
SFMBT1	Scm-like with four MBT domains protein 1	Histone-binding protein, which is part of various corepressor complexes.
XKR9	XK-related protein 9	Phospholipid scramblase that promotes phosphatidylserine exposure on apoptotic cell surface.
ANO1	Anoctamin-1	Calcium-activated chloride channel (CaCC).
COL5A2	Collagen alpha-2(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).
CCAR2	Cell cycle and apoptosis regulator protein 2	Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD c…
CLMP	CXADR-like membrane protein	May be involved in the cell-cell adhesion.
TPPP	Tubulin polymerization-promoting protein	Regulator of microtubule dynamics that plays a key role in myelination by promoting elongation of the myelin sheath.
CTBP2	C-terminal-binding protein 2	Corepressor targeting diverse transcription regulators.
EXOC2	Exocyst complex component 2	Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
KIAA1217	Sickle tail protein homolog	Required for normal development of intervertebral disks.
SRBD1	S1 RNA-binding domain-containing protein 1	DNA- and histone-binding protein that localizes to the central axes of mitotic chromosomes.
TET2	Methylcytosine dioxygenase TET2	Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation.
PLCXD2	PI-PLC X domain-containing protein 2	Catalyzes the hydrolysis of inositol from phosphatidylinositol (1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol), PI).
SPC24	Kinetochore protein Spc24	Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity.
PIAS1	E3 SUMO-protein ligase PIAS1	Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor.
EHBP1	EH domain-binding protein 1	May play a role in actin reorganization.
CHRDL1	Chordin-like protein 1	Antagonizes the function of BMP4 by binding to it and preventing its interaction with receptors.
SND1	Staphylococcal nuclease domain-containing protein 1	Endonuclease that mediates miRNA decay of both protein-free and AGO2-loaded miRNAs.
SERTAD2	SERTA domain-containing protein 2	Acts at E2F-responsive promoters as coregulator to integrate signals provided by PHD- and/or bromodomain-containing transcription factors.
EGFR	Epidermal growth factor receptor	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.
ESR1	Estrogen receptor	Nuclear hormone receptor.
FEZ2	Fasciculation and elongation protein zeta-2	Involved in axonal outgrowth and fasciculation.
FOXL1	Forkhead box protein L1	Transcription factor required for proper proliferation and differentiation in the gastrointestinal epithelium.
FOXP1	Forkhead box protein P1	Transcriptional repressor.
GDF7	Growth/differentiation factor 7	May play an active role in the motor area of the primate neocortex.

Protein-family classification

Druggable: 18 · Difficult: 16 · Unknown: 41 · Druggable fraction: 0.24

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
Nuclear receptor	1	5.2×	0.460
Complement	1	3.6×	0.460
Kinase	5	1.9×	0.460
Antibody/Immunoglobulin	4	1.6×	0.460
Transcription factor	13	1.4×	0.460
Other/Unknown	41	1.0×	0.805
Enzyme (other)	6	1.0×	0.805
Scaffold/PPI	3	0.7×	0.875
Protease	1	0.5×	0.875

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BMP8B	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
BMPR1B	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_dom
BTC	Other/Unknown	no		EGF
SRPX	Complement	yes		Sushi_SCR_CCP_dom, HYR_dom, DUF4174
TCF21	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, E-box_TF_Regulators
THBS2	Other/Unknown	no		EGF, TSP1_rpt, VWF_dom
TMPRSS4	Protease	yes		SRCR, Trypsin_dom, Peptidase_S1A
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
ACOX3	Other/Unknown	no		Acyl-CoA_oxidase_C, AcylCoA_DH/ox_M, AcylCoA_DH/oxidase_NM_dom_sf
UGDH	Enzyme (other)	yes	1.1.1.22	UDP-Glc/GDP-Man_DH_N, 6-PGluconate_DH-like_C_sf, UDP-Glc/GDP-Man_DH_dimer
ZBTB20	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
FBXL7	Other/Unknown	no		F-box_dom, Leu-rich_rpt_Cys-con_subtyp, LRR_dom_sf
HDAC7	Enzyme (other)	yes	3.5.1.98	HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
HHIP	Other/Unknown	no		EGF, Quinoprot_gluc/sorb_DH_b-prop, 6-blade_b-propeller_TolB-like
RBM38	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf
SUGCT	Enzyme (other)	yes	2.8.3.13	CoA-Trfase_fam_III, CoA-Trfase_III_dom_1_sf, CoA-Trfase_III_dom3_sf
TRIM31	Transcription factor	no		Znf_B-box, Znf_RING, Znf_RING/FYVE/PHD
BICD2	Other/Unknown	no		BICD
ACVR2A	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_dom
DLEU7	Other/Unknown	no		DLEU7
MTCH2	Other/Unknown	no		MCP_transmembrane, MCP_dom_sf
MAP3K20	Kinase	yes		Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, SAM
CDKN2B	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor
FGD5	Transcription factor	no		DH_dom, Znf_FYVE, PH_domain
ZNF404	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
GREM1	Other/Unknown	no		DAN_dom, Cys_knot_C, Gremlin-1/2
SFMBT1	Other/Unknown	no		SAM, Mbt, SAM/pointed_sf
XKR9	Other/Unknown	no		XK-rel, XK-related_scramblase
DCBLD1	Other/Unknown	no		FA58C, CUB_dom, LCCL
ANO1	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM
COL5A2	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
FAM185A	Other/Unknown	no		Toastrack_DUF4097
TMEM270	Other/Unknown	no		WBS28
CCAR2	Other/Unknown	no		EF-hand-dom_pair, S1-like_RNA-bd_dom, CCAR1/CCAR2
CLMP	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
TPPP	Other/Unknown	no		TPP/p25, EF-hand-dom_pair
CTBP2	Other/Unknown	no		D-isomer_2_OHA_DH_cat_dom, D-isomer_DH_NAD-bd, D-isomer_DH_CS
EXOC2	Antibody/Immunoglobulin	yes		IPT_dom, Ig-like_fold, Ig_E-set
KIAA1217	Other/Unknown	no		AIP3-like_C, SRCIN1
SRBD1	Other/Unknown	no		S1_domain, YqgF/RNaseH-like_dom, RuvA_2-like
TET2	Other/Unknown	no		2OGFeDO_JBP1/TET_oxygenase_dom, TET1/2/3, TET_oxygenase
TTC27	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC27/Emw1
PLCXD2	Other/Unknown	no		PLipase_C_PInositol-sp_X_dom, PLC-like_Pdiesterase_TIM-brl, PLCXD1/2/3
SPC24	Other/Unknown	no		Ndc80_Spc24
PIAS1	Transcription factor	no		SAP_dom, Znf_MIZ, Znf_RING/FYVE/PHD
KIAA0825	Other/Unknown	no		DUF4495
SLC44A3	Other/Unknown	no		Choline_transptr-like
EHBP1	Other/Unknown	no		CH_dom, NT-C2, bMERB_dom
CHRDL1	Other/Unknown	no		VWF_dom, CHRDL_1/2_C, CHRDL1/2
SND1	Enzyme (other)	yes	3.1.31.1	Thermonucl_AS, Tudor, Staphylococal_nuclease_OB-fold

Expression context

Cohort genes with no expression data: 0.

70 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)	75
unknown	0

Top tissues across cohort

Tissue	Cohort genes
stromal cell of endometrium	9
male germ line stem cell (sensu Vertebrata) in testis	6
primordial germ cell in gonad	5
lower esophagus mucosa	5
mucosa of transverse colon	5
tendon of biceps brachii	5
ventricular zone	5
islet of Langerhans	5
oocyte	5
secondary oocyte	5
calcaneal tendon	4
right coronary artery	4
ganglionic eminence	4
sural nerve	4
cortical plate	4
colonic mucosa	3
mucosa of stomach	3
endothelial cell	3
cervix squamous epithelium	3
left testis	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BMP8B	218	broad	marker	tibia, dorsal root ganglion, trigeminal ganglion
BMPR1B	239	broad	marker	calcaneal tendon, bronchial epithelial cell, cauda epididymis
BTC	201	broad	marker	muscle layer of sigmoid colon, upper leg skin, lower esophagus muscularis layer
SRPX	274	ubiquitous	marker	pericardium, peritoneum, omental fat pad
TCF21	175	broad	marker	primordial germ cell in gonad, right lung, upper lobe of left lung
THBS2	272	ubiquitous	marker	pericardium, right coronary artery, stromal cell of endometrium
TMPRSS4	195	broad	marker	mucosa of transverse colon, lower esophagus mucosa, nasal cavity epithelium
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
ACOX3	235	ubiquitous	marker	lower esophagus mucosa, esophagus mucosa, esophagus squamous epithelium
UGDH	278	ubiquitous	marker	colonic mucosa, mucosa of sigmoid colon, islet of Langerhans
ZBTB20	292	ubiquitous	marker	corpus epididymis, caput epididymis, cauda epididymis
FBXL7	277	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
HDAC7	282	ubiquitous	marker	sural nerve, mucosa of stomach, metanephros cortex
HHIP	206	ubiquitous	marker	corpus callosum, endothelial cell, globus pallidus
RBM38	274	ubiquitous	marker	hindlimb stylopod muscle, gastrocnemius, blood
SUGCT	191	ubiquitous	marker	right adrenal gland cortex, oocyte, right coronary artery
TRIM31	124	tissue_specific	marker	mucosa of transverse colon, rectum, duodenum
BICD2	290	ubiquitous	marker	gingival epithelium, gingiva, hair follicle
ACVR2A	282	ubiquitous	marker	buccal mucosa cell, cervix squamous epithelium, cortical plate
DLEU7	125	tissue_specific	marker	prefrontal cortex, superior frontal gyrus, frontal cortex
MTCH2	142	ubiquitous	marker	left testis, right testis, testis
MAP3K20	267	ubiquitous	marker	heart right ventricle, skeletal muscle tissue of rectus abdominis, biceps brachii
CDKN2B	219	ubiquitous	marker	jejunal mucosa, colonic mucosa, lower esophagus mucosa
FGD5	220	broad	marker	synovial joint, layer of synovial tissue, tendon of biceps brachii
ZNF404	198		yes	right uterine tube, C1 segment of cervical spinal cord, adenohypophysis
GREM1	126	ubiquitous	marker	stromal cell of endometrium, gall bladder, mucosa of stomach
SFMBT1	235	ubiquitous	marker	sperm, male germ cell, sural nerve
XKR9	129	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, duodenum
DCBLD1	218	ubiquitous	marker	secondary oocyte, islet of Langerhans, stromal cell of endometrium
ANO1	214	broad	marker	caput epididymis, seminal vesicle, corpus epididymis

Protein interactions among cohort

Intra-cohort edges: 23.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
ESR1	12,382
SMAD3	6,440
NCAM1	5,075
CTBP2	4,399
MYH11	3,818
CDKN2B	3,431
MDM4	3,431
THBS2	3,405

Intra-cohort edges

A	B	Sources
ACVR2A	GDF7	string_interaction
AP1B1	EGFR	intact
BTC	EGFR	string_interaction
CCAR2	TP53	string_interaction
CDKN2B	TP53	string_interaction
CHRDL1	GREM1	string_interaction
CHRDL1	IRAG1	string_interaction
COL5A2	THBS2	string_interaction
CTBP2	FOXP1	biogrid_interaction, intact
EGFR	FGD5	biogrid_interaction
EGFR	HDAC7	intact
EGFR	HMGA2	intact
EGFR	SLC44A3	string_interaction
FEZ2	SRBD1	string_interaction
FOXP1	TP53	biogrid_interaction
GMDS	UGDH	string_interaction
HMGA2	TP53	biogrid_interaction
HOXC11	SMAD3	biogrid_interaction, intact
KIAA1217	TMEM270	string_interaction
MDM4	TP53	biogrid_interaction, intact, string_interaction
MYO15A	TMPRSS4	string_interaction
PIAS1	TP53	biogrid_interaction
RBM38	TP53	string_interaction

Structural data

PDB: 37 · AlphaFold-only: 38 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ESR1	P03372	478
EGFR	P00533	388
TP53	P04637	313
MERTK	Q12866	42
MDM4	O15151	39
UGDH	O60701	20
AP1B1	Q10567	20
ITGB6	P18564	14
SMAD3	P84022	12
HHIP	Q96QV1	11
SND1	Q7KZF4	11
MAP3K20	Q9NYL2	8
GMDS	O60547	7
NCAM1	P13591	7
HDAC7	Q8WUI4	6
TET2	Q6N021	6
ACVR2A	P27037	5
CTBP2	P56545	5
BTC	P35070	4
SPC24	Q8NBT2	4
EHBP1	Q8NDI1	4
RBM38	Q9H0Z9	3
MTCH2	Q9Y6C9	3
TPPP	O94811	3
THBS2	P35442	2
ZBTB20	Q9HC78	2
SUGCT	Q9HAC7	2
TRIM31	Q9BZY9	2
BICD2	Q8TD16	2
GREM1	O60565	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACOX3	O15254	94.43
TTC27	Q6P3X3	90.66
CDKN2B	P42772	90.12
TMPRSS4	Q9NRS4	88.01
AMPD3	Q01432	85.74
SRPX	P78539	85.37
XKR9	Q5GH70	84.78
FBXL7	Q9UJT9	82.67
SLC44A3	Q8N4M1	81.32
EXOC2	Q96KP1	80.82
PLCXD2	Q0VAA5	80.31
NEMP2	A6NFY4	80.21
FAM185A	Q8N0U4	78.62
CLMP	Q9H6B4	77.52
ANO1	Q5XXA6	77.20
BMP8B	P34820	76.96
SRBD1	Q8N5C6	75.68
DLEU7	Q6UYE1	75.45
SFMBT1	Q9UHJ3	74.62
GSDMC	Q9BYG8	74.59
KIAA0825	Q8IV33	74.33
ZNF404	Q494X3	73.17
ISL1	P61371	72.57
GDF7	Q7Z4P5	72.03
FEZ2	Q9UHY8	71.78
CHRDL1	Q9BU40	69.79
DCBLD1	Q8N8Z6	68.00
TMEM270	Q6UE05	66.82
TCF21	O43680	66.67
HMGA2	P52926	65.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 392. Enrichment computed across 82 evidence-associated genes (51 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 51 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the ureteric bud	3	29.2×	0.021	GREM1, HOXC11, HOXD11
SHC1 events in ERBB2 signaling	3	28.0×	0.021	BTC, EGFR, PRKCA
Signaling by TGFB family members	5	11.3×	0.021	BMPR1B, ACVR2A, CDKN2B, ITGB6, SMAD3
RUNX3 regulates CDKN1A transcription	2	64.0×	0.026	TP53, SMAD3
Signaling by BMP	3	21.0×	0.026	BMPR1B, ACVR2A, CHRDL1
Signaling by ERBB2	3	20.4×	0.026	BTC, EGFR, PRKCA
Oncogene Induced Senescence	3	19.8×	0.026	TP53, CDKN2B, MDM4
Inhibition of Signaling by Overexpressed EGFR	2	49.8×	0.034	BTC, EGFR
EGFR interacts with phospholipase C-gamma	2	44.8×	0.034	BTC, EGFR
EGFR Transactivation by Gastrin	2	44.8×	0.034	EGFR, PRKCA
ERBB2 Activates PTK6 Signaling	2	32.0×	0.049	BTC, EGFR
Signaling by Activin	2	29.9×	0.049	ACVR2A, SMAD3
GRB2 events in EGFR signaling	2	29.9×	0.049	BTC, EGFR
Stabilization of p53	2	29.9×	0.049	TP53, MDM4
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	2	29.9×	0.049	EGFR, ESR1
SHC1 events in EGFR signaling	2	28.0×	0.049	BTC, EGFR
ERBB2 Regulates Cell Motility	2	28.0×	0.049	BTC, EGFR
Signaling by TGF-beta Receptor Complex	3	11.8×	0.049	CDKN2B, ITGB6, SMAD3
PI3K events in ERBB2 signaling	2	26.3×	0.050	BTC, EGFR
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	2	26.3×	0.050	TP53, HMGA2
GAB1 signalosome	2	24.9×	0.051	BTC, EGFR
GRB2 events in ERBB2 signaling	2	24.9×	0.051	BTC, EGFR
Extra-nuclear estrogen signaling	3	10.0×	0.056	BTC, EGFR, ESR1
SUMOylation of transcription factors	2	22.4×	0.058	TP53, PIAS1
Regulation of TP53 Activity through Methylation	2	21.3×	0.059	TP53, MDM4
Developmental Lineage of Mammary Gland Myoepithelial Cells	2	21.3×	0.059	EGFR, MYH11
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	223.9×	0.061	TP53
Signal transduction by L1	2	20.4×	0.061	EGFR, NCAM1
Signaling by NODAL	2	19.5×	0.061	ACVR2A, SMAD3
ECM proteoglycans	3	8.8×	0.061	COL5A2, ITGB6, NCAM1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 74 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
fibroblast proliferation	4	21.2×	0.017	TP53, ESR1, HMGA2, NF1
BMP signaling pathway	5	13.6×	0.017	BMP8B, BMPR1B, ACVR2A, CHRDL1, GDF7
reproductive structure development	2	113.9×	0.017	TCF21, GDF7
morphogenesis of an epithelial fold	2	113.9×	0.017	EGFR, GDF7
activin receptor signaling pathway	3	36.0×	0.017	ACVR2A, GDF7, SMAD3
positive regulation of fibroblast proliferation	4	16.0×	0.017	BTC, EGFR, ESR1, HMGA2
bronchiole development	2	91.1×	0.021	TCF21, ITGB6
adrenal gland development	3	27.3×	0.021	HMGA2, SMAD3, NF1
regulation of mitochondrial membrane permeability involved in apoptotic process	2	75.9×	0.028	TP53, MTCH2
wound healing	4	12.3×	0.028	ITGB6, SMAD3, NF1, PLEC
positive regulation of transcription by RNA polymerase II	14	2.8×	0.029	BMPR1B, TCF21, TP53, ACVR2A, GREM1, CTBP2, TET2, PIAS1 (+6 more)
mesenchymal cell differentiation	2	56.9×	0.039	HMGA2, ISL1
ERBB2-EGFR signaling pathway	2	45.5×	0.039	BTC, EGFR
negative regulation of osteoblast proliferation	2	41.4×	0.039	GREM1, SMAD3
negative regulation of astrocyte differentiation	2	41.4×	0.039	HMGA2, NF1
vagina development	2	41.4×	0.039	ESR1, MERTK
embryonic skeletal joint morphogenesis	2	41.4×	0.039	HOXC11, HOXD11
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	2	41.4×	0.039	SRPX, NF1
forebrain morphogenesis	2	38.0×	0.039	GDF7, NF1
cardiac muscle cell myoblast differentiation	2	38.0×	0.039	GREM1, ISL1
dorsal/ventral pattern formation	3	17.1×	0.039	BMPR1B, HHIP, HOXD11
positive regulation of bone mineralization	3	15.9×	0.039	BMPR1B, ACVR2A, SMAD3
positive regulation of SMAD protein signal transduction	3	15.5×	0.039	ACVR2A, GDF7, SMAD3
neuroblast proliferation	3	14.8×	0.039	TP53, HHIP, NF1
negative regulation of protein catabolic process	3	14.8×	0.039	EGFR, SMAD3, MDM4
DNA damage response, signal transduction by p53 class mediator	3	14.5×	0.039	TP53, RBM38, MDM4
transforming growth factor beta receptor signaling pathway	4	8.6×	0.039	TP53, CDKN2B, ITGB6, SMAD3
cell morphogenesis	4	8.5×	0.039	GREM1, EGFR, ITGB6, PLEC
negative regulation of transcription by RNA polymerase II	12	2.9×	0.039	TCF21, TP53, ZBTB20, HDAC7, CTBP2, PIAS1, ESR1, HMGA2 (+4 more)
negative regulation of neuroblast proliferation	2	32.5×	0.049	TP53, NF1

Therapeutics

Drugs indicated for this disease

22 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Benzocaine	Approved (phase 4)
Betamethasone	Approved (phase 4)
Dexamethasone	Approved (phase 4)
Dibucaine	Approved (phase 4)
Diltiazem	Approved (phase 4)
Fluocinolone Acetonide	Approved (phase 4)
Fluocinonide	Approved (phase 4)
Fluocortolone	Approved (phase 4)
Fluorometholone	Approved (phase 4)
Glycerin	Approved (phase 4)
Hydrocortisone	Approved (phase 4)
Isosorbide Dinitrate	Approved (phase 4)
Lidocaine	Approved (phase 4)
Menthol	Approved (phase 4)
Nitroglycerin	Approved (phase 4)
Phenylephrine	Approved (phase 4)
Pramoxine	Approved (phase 4)
Prednisolone	Approved (phase 4)
Procaine	Approved (phase 4)
Tetracaine	Approved (phase 4)
Triamcinolone	Approved (phase 4)
Zinc Oxide	Approved (phase 4)
Bupivacaine	Phase 3 (in late-stage trials)
Iferanserin	Phase 3 (in late-stage trials)
Metronidazole	Phase 3 (in late-stage trials)
Oxethazaine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Hydrocortisone Acetate, Polidocanol.

Drug target analysis

Approved (phase 4): 13 · Phase ≥3: 14 · Phased (≥1): 19 · Undrugged: 56

Druggability breadth: 31 of 82 evidence-associated genes (38%) 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
BMPR1B	MOMELOTINIB
TP53	NITROFURANTOIN
ACOX3	ALECTINIB
HDAC7	CELECOXIB
ACVR2A	DASATINIB
MAP3K20	PONATINIB
ANO1	NITAZOXANIDE
TET2	VADADUSTAT
EGFR	LEVODOPA
ESR1	CANDESARTAN CILEXETIL
SMAD3	FLUORESCEIN
MDM4	DIOSMIN
MERTK	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
EGFR	175	4
ESR1	162	4
MAP3K20	53	4
MERTK	48	4
BMPR1B	28	4
HDAC7	28	4
MDM4	7	4
ITGB6	5	3
ACVR2A	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	BMPR1B
FEDRATINIB	4	BMPR1B, EGFR, MAP3K20, MERTK
AXITINIB	4	BMPR1B, EGFR, MAP3K20, MERTK
RUXOLITINIB	4	BMPR1B
VANDETANIB	4	BMPR1B, EGFR, MAP3K20, MERTK
GILTERITINIB	4	BMPR1B, EGFR
PAZOPANIB	4	BMPR1B, MERTK
SUNITINIB	4	BMPR1B, EGFR, MERTK
DASATINIB	4	ACVR2A, BMPR1B, EGFR, MAP3K20
QUIZARTINIB	4	BMPR1B, MAP3K20, MERTK
CRIZOTINIB	4	BMPR1B, EGFR, MERTK
NITROFURANTOIN	4	TP53
DIOSMIN	4	MDM4, TP53
VERTEPORFIN	4	MDM4, TP53
CANDESARTAN CILEXETIL	4	ESR1, TP53
DIENESTROL	4	ESR1, TP53
CLOTRIMAZOLE	4	EGFR, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	ESR1, TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 10.

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

Symbol	Assays	Type breakdown
EGFR	6,531	Binding:6211, Functional:173, ADMET:138, Toxicity:9
ESR1	2,435	Binding:2037, Functional:363, ADMET:35
HDAC7	1,710	Binding:1695, ADMET:10, Functional:4, Toxicity:1
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
MERTK	443	Binding:442, Functional:1
MAP3K20	245	Binding:244, Functional:1
BMPR1B	166	Binding:164, ADMET:2
MDM4	149	Binding:148, Functional:1
ACVR2A	98	Binding:98
ITGB6	79	Binding:75, ADMET:2, Functional:2
ANO1	32	Binding:32
TET2	24	Binding:24
SMAD3	24	Binding:18, Functional:6
TMPRSS4	21	Binding:21
CTBP2	10	Binding:10
CCAR2	8	Binding:8
GMDS	8	Binding:8
SND1	7	Binding:7
SFMBT1	6	Binding:6
AMPD3	4	Binding:4
MTCH2	3	Binding:3
ACOX3	2	Binding:2
NCAM1	2	Binding:2
UGDH	1	Binding:1
AP1B1	1	Binding:1
MYO15A	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BMPR1B	2.7.10.2	non-specific protein-tyrosine kinase
UGDH	1.1.1.22	UDP-glucose 6-dehydrogenase
HDAC7	3.5.1.98	histone deacetylase
SUGCT	2.8.3.13	succinate-hydroxymethylglutarate CoA-transferase
ACVR2A	2.7.10.2	non-specific protein-tyrosine kinase
SND1	3.1.31.1	micrococcal nuclease
EGFR	2.7.10.1	receptor protein-tyrosine kinase
GMDS	4.2.1.47	GDP-mannose 4,6-dehydratase
AMPD3	3.5.4.6	AMP deaminase
MERTK	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BMPR1B	166
TP53	869
HDAC7	1,710
MAP3K20	245
EGFR	6,531
ESR1	2,435
MDM4	149
MERTK	443

Pharmacogenomics

Cohort genes with a PharmGKB record: 74; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

29 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	BMPR1B
FEDRATINIB	4	BMPR1B, EGFR, MAP3K20, MERTK
AXITINIB	4	BMPR1B, EGFR, MAP3K20, MERTK
RUXOLITINIB	4	BMPR1B
VANDETANIB	4	BMPR1B, EGFR, MAP3K20, MERTK
GILTERITINIB	4	BMPR1B, EGFR
PAZOPANIB	4	BMPR1B, MERTK
SUNITINIB	4	BMPR1B, EGFR, MERTK
DASATINIB	4	ACVR2A, BMPR1B, EGFR, MAP3K20
QUIZARTINIB	4	BMPR1B, MAP3K20, MERTK
CRIZOTINIB	4	BMPR1B, EGFR, MERTK
NITROFURANTOIN	4	TP53
VERTEPORFIN	4	MDM4, TP53
CANDESARTAN CILEXETIL	4	ESR1, TP53
DIENESTROL	4	ESR1, TP53
CLOTRIMAZOLE	4	EGFR, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	ESR1, TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	13	BMPR1B, TP53, ACOX3, HDAC7, ACVR2A, MAP3K20, ANO1, TET2, EGFR, ESR1 (+3 more)
B	Phased (≥1) drug, not yet approved	6	TMPRSS4, CCAR2, CTBP2, GMDS, AMPD3, ITGB6
C	Druggable family + PDB, no drug	5	UGDH, SUGCT, SND1, AP1B1, NCAM1
D	Druggable family + AlphaFold only, no drug	3	SRPX, CLMP, EXOC2
E	Difficult family or no structure, no drug	48	BMP8B, BTC, TCF21, THBS2, ZBTB20, FBXL7, HHIP, RBM38, TRIM31, BICD2 (+38 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BTC	0	EGFR
CDKN2B	0	TP53
GDF7	0	ACVR2A
HMGA2	0	EGFR
AP1B1	1	EGFR
BMP8B	0	—
SRPX	0	—
TCF21	0	—
THBS2	0	—
UGDH	1	—
ZBTB20	0	—
FBXL7	0	—
HHIP	0	—
RBM38	0	—
SUGCT	0	—
TRIM31	0	—
BICD2	0	—
DLEU7	0	—
MTCH2	3	—
FGD5	0	—
ZNF404	0	—
GREM1	0	—
SFMBT1	6	—
XKR9	0	—
DCBLD1	0	—
COL5A2	0	—
FAM185A	0	—
TMEM270	0	—
CLMP	0	—
TPPP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 159.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	115
PHASE4	17
PHASE3	8
PHASE2/PHASE3	7
PHASE2	7
PHASE1	2
EARLY_PHASE1	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04248205	PHASE4	RECRUITING	Ketamine for Post-operative Analgesia in Hemorrhoidectomy
NCT07128979	PHASE4	RECRUITING	Efficacy and Safety Evaluation of Ruscus Aculeatus L in Patients With Hemorrhoids
NCT00160290	PHASE4	TERMINATED	Trial to Evaluate Effect of Lactulose on Hard Stools in Patients With Hemorrhoids or Anal Fissures
NCT00354029	PHASE4	COMPLETED	Effect of Perioperative i.v. Low-dose S(+) Ketamine
NCT00512044	PHASE4	WITHDRAWN	Local Versus General Anaesthesia in Stapled Hemorrhoidectomy
NCT00841620	PHASE4	COMPLETED	Symptom Control 1-year After Circular Stapler Anopexy or Diathermy Excision for Prolapsed Haemorhoids
NCT01880775	PHASE4	COMPLETED	Discharge Conditions of Spinal Anesthesia With Heavy Prilocaine-Fentanyl and Heavy Bupivacaine-Fentanyl
NCT01881282	PHASE4	COMPLETED	A Comparative Efficacy and Safety Study of Compound Carraghenates Cream With Mayinglong Musk Hemorrhoid Ointment in the Treatment of Hemorrhoids
NCT02104414	PHASE4	TERMINATED	Efficacy of Rectal Infiltration of Exparel for Analgesic Benefit Following Hemorrhoidectomy
NCT02782455	PHASE4	COMPLETED	Calcium Dobesilate vs Flavonoids for the Treatment of Early Hemorrhoidal Disease
NCT02961855	PHASE4	COMPLETED	Efficacy and Safety of CLIFE1 Gel in Benign Anorectal Surgery
NCT03105674	PHASE4	WITHDRAWN	Multi-Drug Analgesia vs. Standard Solution for Anal Surgery
NCT03343509	PHASE4	COMPLETED	Topical Versus Oral Metronidazole Following Excisional Haemorrhoidectomy
NCT03405922	PHASE4	COMPLETED	Perianal Nerval Block in Proctological Interventions
NCT03569930	PHASE4	UNKNOWN	Irritation and Anal Bleeding in Patients Affected by Hemorrhoids.
NCT05519189	PHASE4	COMPLETED	Evaluation of the Value of Perianal Infiltration During Thermodestruction of Haemorrhoidal Disease by Radiofrequency
NCT06872151	PHASE4	COMPLETED	Evaluation of the Effectiveness of a Topical Medical Device in Wound Healing and Symptom Relief in the Postoperative Period of Open Excisional Hemorrhoidectomy (The Emor Study)
NCT00744848	PHASE3	COMPLETED	Study to Evaluate Postoperative Analgesia in Subjects Undergoing Hemorrhoidectomy
NCT00823784	PHASE3	UNKNOWN	Prospective Randomized Trial Comparing THD Versus Stapler Operation for 3rd Degree Hemorrhoids
NCT00861562	PHASE3	UNKNOWN	Clinical Efficacy and Safety Evaluation of the Drug Imescard Compound Water Smartweed Pills
NCT00890721	PHASE3	COMPLETED	Study of Pain Control in Hemorrhoidectomy
NCT01039051	PHASE2/PHASE3	UNKNOWN	Diet and Lifestyle Intervention Study in Postpartum Women in China
NCT01321619	PHASE3	UNKNOWN	Efficacy and Tolerability of the Use of Varicell Compared With Daflon
NCT01961739	PHASE2/PHASE3	UNKNOWN	Topical 2% Lidocaine for the Treatment of Symptomatic Hemorrhoids
NCT02130830	PHASE3	COMPLETED	Topical Anesthesia Versus Placebo to Decrease Pain in Rubber Band Ligation for Treatment of Internal Hemorrhoids
NCT02328144	PHASE3	COMPLETED	Effectiveness of Metronidazole in Pain Control Posthemorrhoidectomy
NCT04188171	PHASE2/PHASE3	UNKNOWN	Sclerotherapy With Polidocanol Foam In The Treatment Of Hemorrhoidal Disease In Patients With Bleeding Disorders
NCT04276298	PHASE2/PHASE3	COMPLETED	Topical Analgesia Post-Haemorrhoidectomy
NCT04329364	PHASE2/PHASE3	UNKNOWN	RCT Comparing Conventional Haemorrhoidectomy With Laser Haemorrhoidoplasty
NCT04675177	PHASE2/PHASE3	COMPLETED	Polidocanol Foam VS Artery Ligation in Hemorrhoidal Disease
NCT05157711	PHASE3	COMPLETED	Clinical Trial of Anusol Ointment for Symptom Relief in Patients With Haemorrhoids
NCT05807425	PHASE2/PHASE3	UNKNOWN	Polidocanol Foam in Hemorrhoidal Disease in Patients With Liver Cirrhosis
NCT07399860	PHASE2	RECRUITING	Botulinum Toxin A Before Hemorrhoidectomy to Prevent Postoperative Pain
NCT01041911	PHASE2	COMPLETED	To Evaluate the Dose Response of 3 Doses of Euphorbia Prostrata in Patients With First and Second Degree Hemorrhoids
NCT01483833	PHASE2	COMPLETED	Efficacy Study of Iferanserin to Treat Hemorrhoids
NCT02301052	PHASE1/PHASE2	UNKNOWN	Evaluation of Allium Ampeloprasum Spp.Iranicum Cream Effect for the Management of Hemorrhoids Symptoms
NCT02353156	PHASE2	UNKNOWN	Posthemorrhoidectomy Pain Management With Electronic Bidet or Sitz Bath
NCT02689856	PHASE2	COMPLETED	Safety and Efficacy of Hydrocortisone and Lidocaine Treatment of Grade I and II Hemorrhoids
NCT04031131	PHASE2	COMPLETED	The Use of Topical Anaesthetic in the Banding of Internal Haemorrhoids
NCT05348200	PHASE2	COMPLETED	Safety and Efficacy of CITI-002 in Adult Patients With Moderate Grade Hemorrhoids

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BUPIVACAINE	4	7
LIDOCAINE	4	3
DIOSMIN	4	2
HYALURONIC ACID	4	1
HYDROCORTISONE ACETATE	4	1
LACTULOSE	4	1
METRONIDAZOLE	4	1
NIFEDIPINE	4	1
PRILOCAINE	4	1
SULFADIAZINE, SILVER	4	1
ZINC OXIDE	4	1
TRIMEBUTINE	3	3
IFERANSERIN	3	1
CHEMBL306147	0	1
CHEMBL4557433	0	1
CHEMBL3039392	0	1