Bladder exstrophy-epispadias-cloacal exstrophy complex
diseaseOn this page
Also known as BEEC
Summary
Bladder exstrophy-epispadias-cloacal exstrophy complex (MONDO:0700039) is a disease with 29 cohort genes. The dominant Reactome pathway is Class B/2 (Secretin family receptors) (4 cohort genes).
At a glance
- Cohort genes: 29
- ClinVar variants: 34
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | bladder exstrophy-epispadias-cloacal exstrophy complex |
| Mondo ID | MONDO:0700039 |
| OMIM | 600057 |
| UMLS | C1838703 |
| MedGen | 374033 |
| GARD | 0026333 |
| Is cancer (heuristic) | no |
Also known as: BEEC
Data availability: 34 ClinVar variants.
Disease family
Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › exstrophy-epispadias complex › bladder exstrophy-epispadias-cloacal exstrophy complex
Related subtypes (3): cloacal exstrophy, bladder exstrophy, epispadias
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
34 retrieved; paginated sample, class counts are floors:
22 uncertain significance, 5 conflicting classifications of pathogenicity, 3 benign, 2 benign/likely benign, 1 likely pathogenic, 1 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 189347 | NM_030753.5(WNT3):c.271T>C (p.Cys91Arg) | LRRC37A2 | Likely pathogenic | no assertion criteria provided |
| 3142105 | NM_001407.3(CELSR3):c.5875G>A (p.Ala1959Thr) | CELSR3 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 328424 | NM_173483.4(CYP4F22):c.160C>T (p.Arg54Cys) | CYP4F22 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 586256 | NM_001009944.3(PKD1):c.2192C>T (p.Pro731Leu) | PKD1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2184324 | NM_018419.3(SOX18):c.766C>T (p.Arg256Trp) | SOX18 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 189351 | NM_025216.3(WNT10A):c.487C>T (p.Arg163Trp) | WNT10A | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2245482 | NM_032208.3(ANTXR1):c.1331G>A (p.Arg444Gln) | ANTXR1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2627998 | NM_001195637.2(CCDC179):c.25G>C (p.Glu9Gln) | CCDC179 | Uncertain significance | criteria provided, single submitter |
| 2628006 | NM_005232.5(EPHA1):c.256A>T (p.Ile86Phe) | EPHA1 | Uncertain significance | criteria provided, single submitter |
| 189354 | NM_003468.4(FZD5):c.267G>A (p.Met89Ile) | FZD5 | Uncertain significance | no assertion criteria provided |
| 373894 | NM_002202.3(ISL1):c.479-4G>A | ISL1 | Uncertain significance | criteria provided, single submitter |
| 374407 | NM_002202.3(ISL1):c.137C>G (p.Ala46Gly) | ISL1 | Uncertain significance | criteria provided, single submitter |
| 2628007 | NM_006618.5(KDM5B):c.4364G>A (p.Arg1455His) | KDM5B | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2628008 | NM_001306080.2(LMO7):c.1883G>C (p.Arg628Thr) | LMO7 | Uncertain significance | criteria provided, single submitter |
| 189350 | NM_004625.4(WNT7A):c.487G>A (p.Ala163Thr) | LOC126806608 | Uncertain significance | no assertion criteria provided |
| 189356 | NM_014045.5(LRP10):c.754G>A (p.Gly252Ser) | LRP10 | Uncertain significance | no assertion criteria provided |
| 189357 | NM_030753.5(WNT3):c.638G>A (p.Gly213Asp) | LRRC37A2 | Uncertain significance | no assertion criteria provided |
| 2628009 | NM_001004749.2(OR51A7):c.64C>T (p.His22Tyr) | MMP26 | Uncertain significance | criteria provided, single submitter |
| 2628010 | NM_023014.1(PRAMEF2):c.1195C>T (p.Arg399Cys) | PRAMEF2 | Uncertain significance | criteria provided, single submitter |
| 2628011 | NM_016277.5(RAB23):c.17T>G (p.Met6Arg) | RAB23 | Uncertain significance | criteria provided, single submitter |
| 2627996 | NM_006652.2(SPINT3):c.149C>T (p.Thr50Met) | SPINT3 | Uncertain significance | criteria provided, single submitter |
| 2627992 | NM_007271.4(STK38):c.630_631del (p.His210fs) | STK38 | Uncertain significance | criteria provided, single submitter |
| 2627993 | NM_001008536.2(TCHHL1):c.1529T>C (p.Val510Ala) | TCHHL1 | Uncertain significance | criteria provided, single submitter |
| 1402802 | NM_003722.5(TP63):c.1530G>T (p.Met510Ile) | TP63 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2627994 | NM_012217.3(TPSD1):c.282G>C (p.Arg94Ser) | TPSD1 | Uncertain significance | criteria provided, single submitter |
| 2627995 | NM_000369.5(TSHR):c.263C>T (p.Thr88Ile) | TSHR | Uncertain significance | criteria provided, single submitter |
| 3236723 | NM_001371589.1(WIZ):c.4637A>G (p.Gln1546Arg) | WIZ | Uncertain significance | criteria provided, single submitter |
| 189352 | NM_004626.3(WNT11):c.947G>A (p.Arg316His) | WNT11 | Uncertain significance | no assertion criteria provided |
| 3236724 | NM_014482.3(BMP10):c.599C>G (p.Thr200Ser) | BMP10 | Benign/Likely benign | criteria provided, multiple submitters, no conflicts |
| 2672914 | NM_001378328.1(CELSR1):c.7313G>A (p.Arg2438Gln) | CELSR1 | Benign/Likely benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 36 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SOX18 | Orphanet:69735 | Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome |
| TSHR | Orphanet:424 | Familial hyperthyroidism due to mutations in TSH receptor |
| TSHR | Orphanet:90673 | Hypothyroidism due to TSH receptor mutations |
| TSHR | Orphanet:95713 | Athyreosis |
| TSHR | Orphanet:95720 | Thyroid hypoplasia |
| TSHR | Orphanet:99819 | Familial gestational hyperthyroidism |
| WNT10A | Orphanet:248 | Autosomal recessive hypohidrotic ectodermal dysplasia |
| WNT10A | Orphanet:2721 | Odonto-onycho-dermal dysplasia |
| WNT10A | Orphanet:50944 | Schöpf-Schulz-Passarge syndrome |
| WNT10A | Orphanet:99798 | Oligodontia |
| RAB23 | Orphanet:65759 | Carpenter syndrome |
| TP63 | Orphanet:1072 | Ankyloblepharon filiforme adnatum-cleft palate syndrome |
| TP63 | Orphanet:141291 | Cleft lip and alveolus |
| TP63 | Orphanet:1896 | EEC syndrome |
| TP63 | Orphanet:199302 | Isolated cleft lip |
| TP63 | Orphanet:199306 | Cleft lip/palate |
| TP63 | Orphanet:2440 | Isolated split hand-split foot malformation |
| TP63 | Orphanet:69085 | Limb-mammary syndrome |
| TP63 | Orphanet:93930 | Classic bladder exstrophy |
| TP63 | Orphanet:978 | ADULT syndrome |
| KDM5B | Orphanet:178469 | Autosomal dominant non-syndromic intellectual disability |
| KDM5B | Orphanet:88616 | Autosomal recessive non-syndromic intellectual disability |
| CELSR1 | Orphanet:569816 | CELSR1-related late-onset primary lymphedema |
| ANTXR1 | Orphanet:2067 | GAPO syndrome |
| CYP4F22 | Orphanet:313 | Lamellar ichthyosis |
| FZD5 | Orphanet:98942 | Coloboma of choroid and retina |
| FZD5 | Orphanet:98943 | Coloboma of eye lens |
| FZD5 | Orphanet:98944 | Coloboma of iris |
| FZD5 | Orphanet:98945 | Coloboma of macula |
| FZD5 | Orphanet:98946 | Coloboma of eyelid |
| FZD5 | Orphanet:98947 | Coloboma of optic disc |
| ISL1 | Orphanet:93930 | Classic bladder exstrophy |
| PKD1 | Orphanet:730 | Autosomal dominant polycystic kidney disease |
| PKD1 | Orphanet:88924 | Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis |
| PRKD1 | Orphanet:276145 | Malignant epithelial tumor of salivary glands |
| PRKD1 | Orphanet:708019 | Congenital heart defect-ectodermal dysplasia- brachydactyly-telangiectasia syndrome |
Cohort genes → proteins
29 cohort genes, 29 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 29 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| SOX18 | HGNC:11194 | ENSG00000203883 | P35713 | Transcription factor SOX-18 | clinvar |
| SPINT3 | HGNC:11248 | ENSG00000101446 | P49223 | Kunitz-type protease inhibitor 3 | clinvar |
| TSHR | HGNC:12373 | ENSG00000165409 | P16473 | Thyrotropin receptor | clinvar |
| WNT11 | HGNC:12776 | ENSG00000085741 | O96014 | Protein Wnt-11 | clinvar |
| WNT6 | HGNC:12785 | ENSG00000115596 | Q9Y6F9 | Protein Wnt-6 | clinvar |
| WNT10A | HGNC:13829 | ENSG00000135925 | Q9GZT5 | Protein Wnt-10a | clinvar |
| TPSD1 | HGNC:14118 | ENSG00000095917 | Q9BZJ3 | Tryptase delta | clinvar |
| MMP26 | HGNC:14249 | ENSG00000167346 | Q9NRE1 | Matrix metalloproteinase-26 | clinvar |
| RAB23 | HGNC:14263 | ENSG00000112210 | Q9ULC3 | Ras-related protein Rab-23 | clinvar |
| LRP10 | HGNC:14553 | ENSG00000197324 | Q7Z4F1 | Low-density lipoprotein receptor-related protein 10 | clinvar |
| TP63 | HGNC:15979 | ENSG00000073282 | Q9H3D4 | Tumor protein 63 | clinvar |
| STK38 | HGNC:17847 | ENSG00000112079 | Q15208 | Serine/threonine-protein kinase 38 | clinvar |
| KDM5B | HGNC:18039 | ENSG00000117139 | Q9UGL1 | Lysine-specific demethylase 5B | clinvar |
| CELSR1 | HGNC:1850 | ENSG00000075275 | Q9NYQ6 | Cadherin EGF LAG seven-pass G-type receptor 1 | clinvar |
| BMP10 | HGNC:20869 | ENSG00000163217 | O95393 | Bone morphogenetic protein 10 | clinvar |
| ANTXR1 | HGNC:21014 | ENSG00000169604 | Q9H6X2 | Anthrax toxin receptor 1 | clinvar |
| CYP4F22 | HGNC:26820 | ENSG00000171954 | Q6NT55 | Ultra-long-chain fatty acid omega-hydroxylase | clinvar |
| PRAMEF2 | HGNC:28841 | ENSG00000120952 | O60811 | PRAME family member 2 | clinvar |
| WIZ | HGNC:30917 | ENSG00000011451 | O95785 | Protein Wiz | clinvar |
| TCHHL1 | HGNC:31796 | ENSG00000182898 | Q5QJ38 | Trichohyalin-like protein 1 | clinvar |
| CELSR3 | HGNC:3230 | ENSG00000008300 | Q9NYQ7 | Cadherin EGF LAG seven-pass G-type receptor 3 | clinvar |
| LRRC37A2 | HGNC:32404 | ENSG00000238083 | A6NM11 | Leucine-rich repeat-containing protein 37A2 | clinvar |
| EPHA1 | HGNC:3385 | ENSG00000146904 | P21709 | Ephrin type-A receptor 1 | clinvar |
| FZD5 | HGNC:4043 | ENSG00000163251 | Q13467 | Frizzled-5 | clinvar |
| CCDC179 | HGNC:44653 | ENSG00000255359 | H3BU77 | Coiled-coil domain-containing protein 179 | clinvar |
| ISL1 | HGNC:6132 | ENSG00000016082 | P61371 | Insulin gene enhancer protein ISL-1 | clinvar |
| LMO7 | HGNC:6646 | ENSG00000136153 | Q8WWI1 | LIM domain only protein 7 | clinvar |
| PKD1 | HGNC:9008 | ENSG00000008710 | P98161 | Polycystin-1 | clinvar |
| PRKD1 | HGNC:9407 | ENSG00000184304 | Q15139 | Serine/threonine-protein kinase D1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| SOX18 | Transcription factor SOX-18 | Transcriptional activator that binds to the consensus sequence 5’-AACAAAG-3’ in the promoter of target genes and plays an essential role in embryonic cardiovascular development and lymphangiogenesis. |
| TSHR | Thyrotropin receptor | Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin. |
| WNT11 | Protein Wnt-11 | Ligand for members of the frizzled family of seven transmembrane receptors. |
| WNT6 | Protein Wnt-6 | Ligand for members of the frizzled family of seven transmembrane receptors. |
| WNT10A | Protein Wnt-10a | Ligand for members of the frizzled family of seven transmembrane receptors. |
| TPSD1 | Tryptase delta | Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type. |
| MMP26 | Matrix metalloproteinase-26 | May hydrolyze collagen type IV, fibronectin, fibrinogen, beta-casein, type I gelatin and alpha-1 proteinase inhibitor. |
| RAB23 | Ras-related protein Rab-23 | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. |
| LRP10 | Low-density lipoprotein receptor-related protein 10 | Probable receptor, which is involved in the internalization of lipophilic molecules and/or signal transduction. |
| TP63 | Tumor protein 63 | Acts as a sequence specific DNA binding transcriptional activator or repressor. |
| STK38 | Serine/threonine-protein kinase 38 | Serine/threonine-protein kinase that acts as a negative regulator of MAP3K1/2 signaling. |
| KDM5B | Lysine-specific demethylase 5B | Histone demethylase that demethylates ‘Lys-4’ of histone H3, thereby playing a central role in histone code. |
| CELSR1 | Cadherin EGF LAG seven-pass G-type receptor 1 | Receptor that may have an important role in cell/cell signaling during nervous system formation. |
| BMP10 | Bone morphogenetic protein 10 | Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expression levels of cardiogenic factors suc… |
| ANTXR1 | Anthrax toxin receptor 1 | Plays a role in cell attachment and migration. |
| CYP4F22 | Ultra-long-chain fatty acid omega-hydroxylase | A cytochrome P450 monooxygenase involved in epidermal ceramide biosynthesis. |
| WIZ | Protein Wiz | May link EHMT1 and EHMT2 histone methyltransferases to the CTBP corepressor machinery. |
| CELSR3 | Cadherin EGF LAG seven-pass G-type receptor 3 | Receptor that may have an important role in cell/cell signaling during nervous system formation. |
| EPHA1 | Ephrin type-A receptor 1 | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. |
| FZD5 | Frizzled-5 | Receptor for Wnt proteins. |
| ISL1 | Insulin gene enhancer protein ISL-1 | DNA-binding transcriptional activator. |
| PKD1 | Polycystin-1 | Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B. |
| PRKD1 | Serine/threonine-protein kinase D1 | Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and tr… |
Protein-family classification
Druggable: 11 · Difficult: 6 · Unknown: 12 · Druggable fraction: 0.38
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 |
|---|---|---|---|
| GPCR | 4 | 3.3× | 0.219 |
| Kinase | 3 | 2.9× | 0.299 |
| Transcription factor | 6 | 1.7× | 0.305 |
| Protease | 2 | 2.5× | 0.328 |
| Antibody/Immunoglobulin | 1 | 1.0× | 0.891 |
| Other/Unknown | 12 | 0.7× | 0.960 |
| Enzyme (other) | 1 | 0.4× | 0.960 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| SOX18 | Transcription factor | no | HMG_box_dom, Sox_C, Sox7/17/18_central | |
| SPINT3 | Other/Unknown | no | Kunitz_BPTI, Prtase_inh_Kunz-CS, Kunitz_BPTI_sf | |
| TSHR | GPCR | yes | GPCR_Rhodpsn, Gphrmn_rcpt_fam, TSH_rcpt | |
| WNT11 | Other/Unknown | no | Wnt, Wnt_CS, Wnt_C | |
| WNT6 | Other/Unknown | no | Wnt, Wnt6, Wnt_CS | |
| WNT10A | Other/Unknown | no | Wnt, Wnt10, Wnt_CS | |
| TPSD1 | Protease | yes | Trypsin_dom, Peptidase_S1A, Peptidase_S1_PA | |
| MMP26 | Protease | yes | 3.4.24.B7 | Pept_M10_metallopeptidase, Peptidase_Metallo, Pept_M10A |
| RAB23 | Other/Unknown | no | Small_GTPase, Small_GTP-bd, P-loop_NTPase | |
| LRP10 | Other/Unknown | no | CUB_dom, LDrepeatLR_classA_rpt, LDLR_class-A_CS | |
| TP63 | Transcription factor | no | SAM, p53_tumour_suppressor, p53-like_TF_DNA-bd_sf | |
| STK38 | Kinase | yes | 2.7.11.1 | Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS |
| KDM5B | Transcription factor | no | 1.14.11.67 | ARID_dom, Znf_PHD, JmjC_dom |
| CELSR1 | GPCR | yes | EGF-type_Asp/Asn_hydroxyl_site, GPS, EGF | |
| BMP10 | Other/Unknown | no | TGF-b_propeptide, TGF-b_C, TGF-beta-like | |
| ANTXR1 | Other/Unknown | no | VWF_A, Anthrax_toxin_rcpt_C, Anthrax_toxin_rcpt_extracel | |
| CYP4F22 | Enzyme (other) | yes | 1.14.14.177 | Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS |
| PRAMEF2 | Other/Unknown | no | PRAME, LRR_dom_sf, LRRC14/PRAME | |
| WIZ | Transcription factor | no | Znf_C2H2_type, Znf_C2H2_sf, Transcr_Reg_ZincFinger | |
| TCHHL1 | Other/Unknown | no | EF-hand-dom_pair, S100_Ca-bd_sub, S-100_dom | |
| CELSR3 | GPCR | yes | GPS, EGF, GPCR_2_secretin-like | |
| LRRC37A2 | Other/Unknown | no | Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRRC37 | |
| EPHA1 | Kinase | yes | 2.7.10.1 | Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom |
| FZD5 | GPCR | yes | Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM | |
| CCDC179 | Other/Unknown | no | ||
| ISL1 | Transcription factor | no | HD, Znf_LIM, Homeodomain-like_sf | |
| LMO7 | Transcription factor | no | PDZ, CH_dom, Znf_LIM | |
| PKD1 | Antibody/Immunoglobulin | yes | GPS, LRRNT, PC1 | |
| PRKD1 | Kinase | yes | 2.7.11.13 | Prot_kinase_dom, PH_domain, PKC_DAG/PE |
Expression context
Cohort genes with no expression data: 0.
23 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 2 |
| moderate (6-20) | 0 |
| broad (>20) | 27 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| lower esophagus mucosa | 5 |
| secondary oocyte | 3 |
| ventricular zone | 3 |
| sural nerve | 3 |
| cerebellar hemisphere | 3 |
| apex of heart | 2 |
| right lung | 2 |
| cauda epididymis | 2 |
| male germ cell | 2 |
| sperm | 2 |
| bone marrow cell | 2 |
| male germ line stem cell (sensu Vertebrata) in testis | 2 |
| decidua | 2 |
| stromal cell of endometrium | 2 |
| upper arm skin | 2 |
| palpebral conjunctiva | 2 |
| left testis | 2 |
| skin of leg | 2 |
| colonic epithelium | 2 |
| cortical plate | 2 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SOX18 | 165 | broad | marker | apex of heart, right lung, left uterine tube |
| SPINT3 | 33 | tissue_specific | marker | cauda epididymis, sperm, male germ cell |
| TSHR | 169 | broad | marker | right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland |
| WNT11 | 178 | broad | marker | omental fat pad, peritoneum, adipose tissue of abdominal region |
| WNT6 | 152 | broad | yes | endometrium epithelium, tibial nerve, Brodmann (1909) area 10 |
| WNT10A | 151 | broad | marker | primordial germ cell in gonad, lower esophagus mucosa, bone marrow cell |
| TPSD1 | 122 | tissue_specific | marker | mucosa of transverse colon, right lung, lower esophagus muscularis layer |
| MMP26 | 38 | tissue_specific | marker | buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, endometrium |
| RAB23 | 264 | ubiquitous | marker | cauda epididymis, saphenous vein, secondary oocyte |
| LRP10 | 284 | ubiquitous | marker | stromal cell of endometrium, decidua, right coronary artery |
| TP63 | 207 | broad | marker | upper leg skin, skin of hip, upper arm skin |
| STK38 | 288 | ubiquitous | marker | palpebral conjunctiva, oocyte, secondary oocyte |
| KDM5B | 272 | ubiquitous | marker | sperm, male germ cell, left testis |
| CELSR1 | 224 | ubiquitous | marker | ventricular zone, lower esophagus mucosa, bronchial epithelial cell |
| BMP10 | 90 | tissue_specific | marker | cardiac muscle of right atrium, right atrium auricular region, cardiac atrium |
| ANTXR1 | 270 | ubiquitous | marker | stromal cell of endometrium, decidua, palpebral conjunctiva |
| CYP4F22 | 103 | tissue_specific | marker | lower esophagus mucosa, upper arm skin, skin of leg |
| PRAMEF2 | 0 | yes | colonic epithelium, sural nerve, ventricular zone | |
| WIZ | 259 | ubiquitous | marker | cortical plate, ganglionic eminence, right testis |
| TCHHL1 | 4 | tissue_specific | marker | sural nerve, bone marrow cell, colonic epithelium |
| CELSR3 | 209 | broad | yes | right hemisphere of cerebellum, cortical plate, cerebellar hemisphere |
| LRRC37A2 | 134 | yes | right uterine tube, right testis, cerebellar hemisphere | |
| EPHA1 | 160 | broad | yes | lower esophagus mucosa, esophagus mucosa, skin of leg |
| FZD5 | 256 | ubiquitous | marker | jejunal mucosa, mucosa of sigmoid colon, colonic mucosa |
| CCDC179 | 47 | tissue_specific | yes | male germ line stem cell (sensu Vertebrata) in testis, left testis, testis |
| ISL1 | 148 | broad | marker | secondary oocyte, cervix squamous epithelium, islet of Langerhans |
| LMO7 | 214 | ubiquitous | marker | sural nerve, lower esophagus mucosa, apex of heart |
| PKD1 | 290 | marker | right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex | |
| PRKD1 | 239 | ubiquitous | marker | ventricular zone, seminal vesicle, thoracic aorta |
Protein interactions among cohort
Intra-cohort edges: 4.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| KDM5B | 3,722 |
| EPHA1 | 2,975 |
| TP63 | 2,893 |
| STK38 | 2,465 |
| PRAMEF2 | 2,317 |
| PRKD1 | 2,131 |
| ANTXR1 | 2,039 |
| WNT11 | 2,017 |
| LMO7 | 1,976 |
| TSHR | 1,672 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| FZD5 | WNT10A | string_interaction |
| FZD5 | WNT11 | string_interaction |
| FZD5 | WNT6 | string_interaction |
| PKD1 | PRKD1 | string_interaction |
Structural data
PDB: 13 · AlphaFold-only: 16 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| KDM5B | Q9UGL1 | 56 |
| TP63 | Q9H3D4 | 26 |
| PKD1 | P98161 | 13 |
| TSHR | P16473 | 9 |
| BMP10 | O95393 | 8 |
| RAB23 | Q9ULC3 | 6 |
| ANTXR1 | Q9H6X2 | 5 |
| EPHA1 | P21709 | 4 |
| FZD5 | Q13467 | 4 |
| WIZ | O95785 | 3 |
| STK38 | Q15208 | 2 |
| CELSR1 | Q9NYQ6 | 2 |
| LMO7 | Q8WWI1 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| CYP4F22 | Q6NT55 | 93.59 |
| SPINT3 | P49223 | 93.13 |
| WNT11 | O96014 | 90.35 |
| TPSD1 | Q9BZJ3 | 85.89 |
| WNT6 | Q9Y6F9 | 83.62 |
| WNT10A | Q9GZT5 | 82.36 |
| PRAMEF2 | O60811 | 81.46 |
| CCDC179 | H3BU77 | 80.41 |
| MMP26 | Q9NRE1 | 79.33 |
| ISL1 | P61371 | 72.57 |
| PRKD1 | Q15139 | 68.99 |
| LRP10 | Q7Z4F1 | 67.84 |
| SOX18 | P35713 | 63.44 |
| LRRC37A2 | A6NM11 | 42.32 |
| TCHHL1 | Q5QJ38 | 42.28 |
| CELSR3 | Q9NYQ7 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 87. Enrichment computed across 29 evidence-associated genes (18 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 18 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Class B/2 (Secretin family receptors) | 4 | 42.3× | 2e-04 | WNT11, WNT6, WNT10A, FZD5 |
| WNT ligand biogenesis and trafficking | 3 | 70.5× | 4e-04 | WNT11, WNT6, WNT10A |
| Defective CYP4F22 causes ARCI5 | 1 | 634.4× | 0.046 | CYP4F22 |
| TFAP2 (AP-2) family regulates transcription of cell cycle factors | 1 | 126.9× | 0.094 | KDM5B |
| Signaling by RNF43 mutants | 1 | 70.5× | 0.094 | FZD5 |
| Activation of PUMA and translocation to mitochondria | 1 | 63.4× | 0.094 | TP63 |
| Incretin synthesis, secretion, and inactivation | 1 | 57.7× | 0.094 | ISL1 |
| Miscellaneous substrates | 1 | 52.9× | 0.094 | CYP4F22 |
| Eicosanoids | 1 | 52.9× | 0.094 | CYP4F22 |
| Hormone ligand-binding receptors | 1 | 52.9× | 0.094 | TSHR |
| Uptake and function of anthrax toxins | 1 | 52.9× | 0.094 | ANTXR1 |
| TP53 Regulates Transcription of Caspase Activators and Caspases | 1 | 52.9× | 0.094 | TP63 |
| TP53 Regulates Transcription of Death Receptors and Ligands | 1 | 52.9× | 0.094 | TP63 |
| POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation | 1 | 48.8× | 0.094 | EPHA1 |
| Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) | 1 | 48.8× | 0.094 | ISL1 |
| WNT5A-dependent internalization of FZD2, FZD5 and ROR2 | 1 | 48.8× | 0.094 | FZD5 |
| Regulation of TP53 Activity through Association with Co-factors | 1 | 45.3× | 0.094 | TP63 |
| RHOBTB GTPase Cycle | 1 | 45.3× | 0.094 | STK38 |
| TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain | 1 | 42.3× | 0.094 | TP63 |
| Developmental Lineage of Mammary Stem Cells | 1 | 42.3× | 0.094 | TP63 |
| Fatty acids | 1 | 39.6× | 0.094 | CYP4F22 |
| Maternal to zygotic transition (MZT) | 1 | 39.6× | 0.094 | KDM5B |
| Ca2+ pathway | 2 | 19.8× | 0.094 | WNT11, FZD5 |
| Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 1 | 35.2× | 0.101 | KDM5B |
| Synthesis of Leukotrienes (LT) and Eoxins (EX) | 1 | 31.7× | 0.101 | CYP4F22 |
| TP53 Regulates Transcription of Genes Involved in Cytochrome C Release | 1 | 30.2× | 0.101 | TP63 |
| Developmental Lineage of Mammary Gland Myoepithelial Cells | 1 | 30.2× | 0.101 | TP63 |
| Regulation of FZD by ubiquitination | 1 | 28.8× | 0.101 | FZD5 |
| VxPx cargo-targeting to cilium | 1 | 28.8× | 0.101 | PKD1 |
| Formation of the ureteric bud | 1 | 27.6× | 0.101 | WNT11 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 25 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| canonical Wnt signaling pathway | 5 | 30.6× | 2e-04 | WNT11, WNT6, WNT10A, FZD5, ISL1 |
| cloacal septation | 2 | 674.1× | 4e-04 | WNT11, TP63 |
| mesonephric duct development | 2 | 269.6× | 0.002 | WNT11, PKD1 |
| positive regulation of sarcomere organization | 2 | 224.7× | 0.002 | BMP10, PRKD1 |
| negative regulation of mesenchymal cell proliferation | 2 | 224.7× | 0.002 | WNT11, ISL1 |
| Wnt signaling pathway, planar cell polarity pathway | 3 | 54.7× | 0.002 | WNT11, CELSR1, CELSR3 |
| outflow tract morphogenesis | 3 | 36.8× | 0.004 | SOX18, WNT11, ISL1 |
| cell fate commitment | 3 | 35.5× | 0.004 | WNT11, WNT6, WNT10A |
| neuron differentiation | 4 | 16.1× | 0.004 | WNT11, WNT6, WNT10A, FZD5 |
| secondary heart field specification | 2 | 122.6× | 0.004 | WNT11, ISL1 |
| negative regulation of intracellular estrogen receptor signaling pathway | 2 | 89.9× | 0.007 | TP63, ISL1 |
| establishment of planar polarity | 2 | 84.3× | 0.008 | TP63, CELSR1 |
| positive regulation of gene expression | 5 | 7.8× | 0.011 | WNT6, WNT10A, KDM5B, BMP10, PRKD1 |
| axonogenesis | 3 | 19.3× | 0.013 | CELSR1, CELSR3, ISL1 |
| ventricular cardiac muscle tissue morphogenesis | 2 | 56.2× | 0.014 | BMP10, ISL1 |
| angiogenesis | 4 | 10.0× | 0.015 | SOX18, EPHA1, FZD5, PRKD1 |
| homophilic cell-cell adhesion | 3 | 16.9× | 0.016 | CELSR1, CELSR3, PKD1 |
| ectoderm and mesoderm interaction | 1 | 674.1× | 0.019 | TP63 |
| axis specification | 1 | 674.1× | 0.019 | WNT6 |
| epidermal cell division | 1 | 674.1× | 0.019 | TP63 |
| thyroid-stimulating hormone signaling pathway | 1 | 674.1× | 0.019 | TSHR |
| metanephric distal tubule morphogenesis | 1 | 674.1× | 0.019 | PKD1 |
| positive regulation of macrophage colony-stimulating factor production | 1 | 674.1× | 0.019 | ISL1 |
| cellular response to thyrotropin-releasing hormone | 1 | 674.1× | 0.019 | TSHR |
| regulation of estradiol secretion | 1 | 674.1× | 0.019 | KDM5B |
| hair follicle morphogenesis | 2 | 39.6× | 0.019 | WNT10A, TP63 |
| skin development | 2 | 35.5× | 0.019 | WNT10A, PKD1 |
| positive regulation of angiogenesis | 3 | 13.8× | 0.019 | EPHA1, ISL1, PRKD1 |
| positive regulation of transcription by RNA polymerase II | 7 | 4.2× | 0.019 | SOX18, TP63, FZD5, ISL1, LMO7, PKD1, PRKD1 |
| cell-cell adhesion mediated by cadherin | 2 | 32.9× | 0.021 | CELSR1, CELSR3 |
Therapeutics
Drug target analysis
Approved (phase 4): 4 · Phase ≥3: 6 · Phased (≥1): 6 · Undrugged: 23
Druggability breadth: 12 of 29 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 |
|---|---|
| TSHR | LEVOSALBUTAMOL |
| STK38 | FEDRATINIB |
| EPHA1 | PONATINIB |
| PRKD1 | INGENOL MEBUTATE |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| TSHR | 354 | 4 |
| EPHA1 | 37 | 4 |
| PRKD1 | 26 | 4 |
| STK38 | 9 | 4 |
| MMP26 | 2 | 3 |
| KDM5B | 2 | 3 |
| SOX18 | 0 | 0 |
| SPINT3 | 0 | 0 |
| WNT11 | 0 | 0 |
| WNT6 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| LEVOSALBUTAMOL | 4 | TSHR |
| PROGESTERONE | 4 | TSHR |
| DICLOFENAC SODIUM | 4 | TSHR |
| CLOTRIMAZOLE | 4 | TSHR |
| DAPSONE | 4 | TSHR |
| COLCHICINE | 4 | TSHR |
| OXAPROZIN | 4 | TSHR |
| BUMETANIDE | 4 | TSHR |
| GLIPIZIDE | 4 | TSHR |
| CARBAMAZEPINE | 4 | TSHR |
| METHYL SALICYLATE | 4 | TSHR |
| PHENELZINE | 4 | TSHR |
| EDROPHONIUM | 4 | TSHR |
| SULFAPHENAZOLE | 4 | TSHR |
| AMOXAPINE | 4 | TSHR |
| PYRIDOSTIGMINE | 4 | TSHR |
| ACETAMINOPHEN | 4 | TSHR |
| DICYCLOMINE | 4 | TSHR |
| IODIPAMIDE | 4 | TSHR |
| TESTOSTERONE PROPIONATE | 4 | TSHR |
| TETRABENAZINE | 4 | TSHR |
| CELECOXIB | 4 | TSHR |
| PROPANTHELINE | 4 | TSHR |
| BENOXINATE | 4 | TSHR |
| NICARDIPINE HYDROCHLORIDE | 4 | TSHR |
| PYRITHIONE ZINC | 4 | TSHR |
| GUANABENZ ACETATE | 4 | TSHR |
| PROPIOLACTONE | 4 | TSHR |
| CHLOROTRIANISENE | 4 | TSHR |
| PHENOXYBENZAMINE HYDROCHLORIDE | 4 | TSHR |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 6.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| PRKD1 | 660 | Binding:650, Functional:10 |
| EPHA1 | 284 | Binding:284 |
| STK38 | 153 | Binding:153 |
| KDM5B | 146 | Binding:146 |
| TPSD1 | 35 | Binding:35 |
| TSHR | 33 | Functional:24, Binding:9 |
| PKD1 | 27 | Binding:27 |
| WIZ | 15 | Binding:10, Functional:5 |
| SOX18 | 11 | Binding:11 |
| MMP26 | 8 | Binding:8 |
| FZD5 | 8 | Functional:6, Binding:2 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| MMP26 | 3.4.24.B7 | |
| STK38 | 2.7.11.1 | non-specific serine/threonine protein kinase |
| KDM5B | 1.14.11.67 | [histone H3]-trimethyl-L-lysine4 demethylase |
| CYP4F22 | 1.14.14.177 | ultra-long-chain fatty acid omega-hydroxylase |
| EPHA1 | 2.7.10.1 | receptor protein-tyrosine kinase |
| PRKD1 | 2.7.11.13 | protein kinase C |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| STK38 | 153 |
| KDM5B | 146 |
| EPHA1 | 284 |
| PRKD1 | 660 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 29; 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) |
|---|---|---|
| LEVOSALBUTAMOL | 4 | TSHR |
| PROGESTERONE | 4 | TSHR |
| DICLOFENAC SODIUM | 4 | TSHR |
| CLOTRIMAZOLE | 4 | TSHR |
| DAPSONE | 4 | TSHR |
| COLCHICINE | 4 | TSHR |
| OXAPROZIN | 4 | TSHR |
| BUMETANIDE | 4 | TSHR |
| GLIPIZIDE | 4 | TSHR |
| CARBAMAZEPINE | 4 | TSHR |
| METHYL SALICYLATE | 4 | TSHR |
| PHENELZINE | 4 | TSHR |
| EDROPHONIUM | 4 | TSHR |
| SULFAPHENAZOLE | 4 | TSHR |
| AMOXAPINE | 4 | TSHR |
| PYRIDOSTIGMINE | 4 | TSHR |
| ACETAMINOPHEN | 4 | TSHR |
| DICYCLOMINE | 4 | TSHR |
| IODIPAMIDE | 4 | TSHR |
| TESTOSTERONE PROPIONATE | 4 | TSHR |
| TETRABENAZINE | 4 | TSHR |
| CELECOXIB | 4 | TSHR |
| PROPANTHELINE | 4 | TSHR |
| BENOXINATE | 4 | TSHR |
| NICARDIPINE HYDROCHLORIDE | 4 | TSHR |
| PYRITHIONE ZINC | 4 | TSHR |
| GUANABENZ ACETATE | 4 | TSHR |
| PROPIOLACTONE | 4 | TSHR |
| CHLOROTRIANISENE | 4 | TSHR |
| PHENOXYBENZAMINE HYDROCHLORIDE | 4 | TSHR |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 4 | TSHR, STK38, EPHA1, PRKD1 |
| B | Phased (≥1) drug, not yet approved | 2 | MMP26, KDM5B |
| C | Druggable family + PDB, no drug | 3 | CELSR1, FZD5, PKD1 |
| D | Druggable family + AlphaFold only, no drug | 3 | TPSD1, CYP4F22, CELSR3 |
| E | Difficult family or no structure, no drug | 17 | SOX18, SPINT3, WNT11, WNT6, WNT10A, RAB23, LRP10, TP63, BMP10, ANTXR1 (+7 more) |
Undrugged target profiles
23 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| PKD1 | 27 | PRKD1 |
| SOX18 | 11 | — |
| SPINT3 | 0 | — |
| WNT11 | 0 | — |
| WNT6 | 0 | — |
| WNT10A | 0 | — |
| TPSD1 | 35 | — |
| RAB23 | 0 | — |
| LRP10 | 0 | — |
| TP63 | 0 | — |
| CELSR1 | 0 | — |
| BMP10 | 0 | — |
| ANTXR1 | 0 | — |
| CYP4F22 | 0 | — |
| PRAMEF2 | 0 | — |
| WIZ | 15 | — |
| TCHHL1 | 0 | — |
| CELSR3 | 0 | — |
| LRRC37A2 | 0 | — |
| FZD5 | 8 | — |
| CCDC179 | 0 | — |
| ISL1 | 0 | — |
| LMO7 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.