Summary
Renal agenesis, unilateral (MONDO:0019636) is a disease with 13 cohort genes (32 GWAS associations across 2 studies) and 1 clinical trial.
At a glance
- Prevalence: 1-5 / 10 000 (Worldwide) [Orphanet-validated]
- Cohort genes: 13
- GWAS associations: 32
- ClinVar variants: 7
- Clinical trials: 1
Clinical features
Epidemiology
Prevalence records
1 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|
| Prevalence at birth | 1-5 / 10 000 | 50 | Worldwide | Validated |
Identifiers
Disease identifiers
| Field | Value |
|---|
| Canonical name | renal agenesis, unilateral |
| Mondo ID | MONDO:0019636 |
| Orphanet | 93100 |
| ICD-10-CM | Q60.0 |
| ICD-11 | 760295498 |
| NCIT | C101220 |
| UMLS | C0266294 |
| MedGen | 75607 |
| GARD | 0016804 |
| MedDRA | 10053624 |
| Is cancer (heuristic) | no |
Also known as: congenital single kidney · congenital solitary kidney · unilateral renal agenesis
Data availability: 7 ClinVar variants · 32 GWAS associations (2 studies) · 8 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › renal agenesis › renal agenesis, unilateral
Related subtypes (5): renal hypodysplasia/aplasia 2, bilateral renal agenesis, renal hypodysplasia/aplasia 1, renal hypodysplasia/aplasia 3, renal hypodysplasia/aplasia 4
Genetics & variants
GWAS landscape
32 GWAS associations across 2 studies. Top hits map to 15 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|
| rs184382636 | 1e-10 | LINC01898 - LINC01893 | ? | 12.9 |
| rs140804918 | 1e-08 | CDHR17P | ? | 3.1 |
| rs73282857 | 6e-08 | C5orf24 - TXNDC15 | ? | 7 |
| rs182382581 | 9e-08 | HMGB1P5 - FCRL4P1 | ? | 5.04 |
| rs192152837 | 4e-07 | LNCRNA-IUR - FAM76B | ? | 6.35 |
| rs146557102 | 6e-07 | PPM1A | ? | 2.96 |
| rs181072352 | 1e-06 | LINC02450 - MRPS36P5 | ? | 10.4 |
| rs181945740 | 1e-06 | CAST | ? | 5.9 |
| rs148413365 | 2e-06 | KCTD20 | ? | 0.51 |
| rs190937828 | 2e-06 | CPAMD8P1 - U3 | ? | 2.3 |
| rs11229723 | 2e-06 | GLYATL1-AS1, GLYATL1 | ? | 4.41 |
| rs9547854 | 2e-06 | RPS12P24 - LINC01048 | ? | 1.97 |
| rs201841698 | 2e-06 | TNNC2 | ? | 3.4 |
| rs190397903 | 2e-06 | RNU6-351P - TET2 | ? | 5.23 |
| rs144419778 | 3e-06 | TBC1D4 | ? | 1.71 |
| rs145922969 | 3e-06 | CYSTM1, PFDN1 | ? | 3.2 |
| rs10433490 | 4e-06 | P3H2-AS1 | ? | 0.53 |
| rs1325019515 | 5e-06 | MIR4686 - ASCL2 | ? | 1.61 |
| rs148251525 | 5e-06 | LINC01550 - LINC02295 | ? | 2.08 |
| rs2830456 | 5e-06 | CYYR1 - ADAMTS1 | ? | 0.63 |
| rs6126804 | 6e-06 | TSHZ2 | ? | 3.3 |
| rs60001082 | 7e-06 | ZNF485 - ZNF32-AS2 | ? | 2 |
| rs554290784 | 7e-06 | SLC6A13 - KDM5A | ? | 5.59 |
| rs73172143 | 7e-06 | SYN3 | ? | 1.88 |
| rs146356251 | 7e-06 | CSN2 - STATH | ? | 4.84 |
| rs138487999 | 7e-06 | HOMER1 | ? | 2.84 |
| rs11406716 | 8e-06 | BTBD8 - C1orf146 | ? | 1.64 |
| rs10112722 | 8e-06 | ST3GAL1-DT - LINC03024 | ? | 1.55 |
| rs111283115 | 8e-06 | ISG20 - ACAN | ? | 0.65 |
| rs140198115 | 8e-06 | IFI44 - ADGRL4 | ? | 3.79 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|
| GCST90244791 | Groen In ’t Woud S | 2022 | 403 | 0 | A Genome-Wide Association Study into the Aetiology of Congenital Solitary Functioning Kidney. |
| GCST90244792 | Groen In ’t Woud S | 2022 | 403 | 4,366 | A Genome-Wide Association Study into the Aetiology of Congenital Solitary Functioning Kidney. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|
| Tier 1: coding | 0 |
| Tier 2: splice/UTR | 0 |
| Tier 3: regulatory | 0 |
| Tier 4: intronic/intergenic | 32 |
MAF distribution
| Bucket | Variants |
|---|
| common (>=0.05) | 21 |
| low_freq (0.01-0.05) | 0 |
| rare (<0.01) | 0 |
| unknown | 11 |
Functional consequences
| Consequence | Count |
|---|
| intron_variant | 16 |
| intergenic_variant | 14 |
| non_coding_transcript_exon_variant | 2 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|
| rs184382636 | 18 | 75924335 | C>T | | intergenic_variant | LINC01898 - LINC01893 | 1e-10 | Tier 4: intronic/intergenic |
| rs140804918 | 7 | 81599574 | C>G,T | 0.05 | intron_variant | CDHR17P | 1e-08 | Tier 4: intronic/intergenic |
| rs73282857 | 5 | 134863368 | A>G | 0.05 | non_coding_transcript_exon_variant | C5orf24 - TXNDC15 | 6e-08 | Tier 4: intronic/intergenic |
| rs182382581 | 3 | 22447149 | T>C | | intergenic_variant | HMGB1P5 - FCRL4P1 | 9e-08 | Tier 4: intronic/intergenic |
| rs192152837 | 11 | 95428080 | C>T | | intergenic_variant | LNCRNA-IUR - FAM76B | 4e-07 | Tier 4: intronic/intergenic |
| rs146557102 | 14 | 60261390 | CTGAATTTTGAATTTTA>C | 0.05 | intron_variant | PPM1A | 6e-07 | Tier 4: intronic/intergenic |
| rs181072352 | 12 | 42862584 | T>A | | intergenic_variant | LINC02450 - MRPS36P5 | 1e-06 | Tier 4: intronic/intergenic |
| rs181945740 | 5 | 96680198 | A>T | | intron_variant | CAST | 1e-06 | Tier 4: intronic/intergenic |
| rs148413365 | 6 | 36483940 | ATTTT>A,AT,ATT,ATTT,ATTTTT,ATTTTTT,ATTTTTTT,ATTTTTTTT | 0.05 | intron_variant | KCTD20 | 2e-06 | Tier 4: intronic/intergenic |
| rs190937828 | 7 | 9975029 | T>A,C | 0.05 | intron_variant | CPAMD8P1 - U3 | 2e-06 | Tier 4: intronic/intergenic |
| rs11229723 | 11 | 59000032 | A>G,T | 0.05 | intron_variant | GLYATL1-AS1, GLYATL1 | 2e-06 | Tier 4: intronic/intergenic |
| rs9547854 | 13 | 37426454 | C>A,T | 0.05 | intergenic_variant | RPS12P24 - LINC01048 | 2e-06 | Tier 4: intronic/intergenic |
| rs201841698 | 20 | 45825152 | AT>A,ATT | 0.05 | intron_variant | TNNC2 | 2e-06 | Tier 4: intronic/intergenic |
| rs190397903 | 4 | 105130719 | G>A | | intergenic_variant | RNU6-351P - TET2 | 2e-06 | Tier 4: intronic/intergenic |
| rs144419778 | 13 | 75375767 | AC>A,ACC,ACCC,ACCCC,ACCCCC,ACCCCCC,ACCCCCCC,ACCCCCCCC | 0.05 | intron_variant | TBC1D4 | 3e-06 | Tier 4: intronic/intergenic |
| rs145922969 | 5 | 140266491 | C>A,T | | intron_variant | CYSTM1, PFDN1 | 3e-06 | Tier 4: intronic/intergenic |
| rs10433490 | 3 | 190194433 | G>A,C | 0.05 | intron_variant | P3H2-AS1 | 4e-06 | Tier 4: intronic/intergenic |
| rs1325019515 | 11 | 2254658 | C>T | | intergenic_variant | MIR4686 - ASCL2 | 5e-06 | Tier 4: intronic/intergenic |
| rs148251525 | 14 | 98048188 | A>G,T | 0.05 | intergenic_variant | LINC01550 - LINC02295 | 5e-06 | Tier 4: intronic/intergenic |
| rs2830456 | 21 | 26749827 | T>C | 0.05 | intergenic_variant | CYYR1 - ADAMTS1 | 5e-06 | Tier 4: intronic/intergenic |
| rs6126804 | 20 | 53268773 | T>A | 0.05 | intron_variant | TSHZ2 | 6e-06 | Tier 4: intronic/intergenic |
| rs60001082 | 10 | 43621602 | TA>T | 0.05 | intergenic_variant | ZNF485 - ZNF32-AS2 | 7e-06 | Tier 4: intronic/intergenic |
| rs554290784 | 12 | 276680 | G>A | | non_coding_transcript_exon_variant | SLC6A13 - KDM5A | 7e-06 | Tier 4: intronic/intergenic |
| rs73172143 | 22 | 32549626 | C>A,T | 0.05 | intron_variant | SYN3 | 7e-06 | Tier 4: intronic/intergenic |
| rs146356251 | 4 | 69970431 | A>G | | intergenic_variant | CSN2 - STATH | 7e-06 | Tier 4: intronic/intergenic |
| rs138487999 | 5 | 79378563 | T>C | 0.05 | intron_variant | HOMER1 | 7e-06 | Tier 4: intronic/intergenic |
| rs11406716 | 1 | 92197720 | CAAAAAAA>C,CAA,CAAA,CAAAA,CAAAAA,CAAAAAA,CAAAAAAAA,CAAAAAAAAA,CAAAAAAAAAA,CAAAAAAAAAAA,CAAAAAAAAAAAA,CAAAAAAAAAAAAA,CAAAAAAAAAAAAAA,CAAAAAAAAAAAAAAAA,CAAAAAAAAAAAAAAAAA | 0.05 | intergenic_variant | BTBD8 - C1orf146 | 8e-06 | Tier 4: intronic/intergenic |
| rs10112722 | 8 | 133582989 | T>G | 0.05 | intergenic_variant | ST3GAL1-DT - LINC03024 | 8e-06 | Tier 4: intronic/intergenic |
| rs111283115 | 15 | 88801632 | A>C,G,T | 0.05 | intron_variant | ISG20 - ACAN | 8e-06 | Tier 4: intronic/intergenic |
| rs140198115 | 1 | 78851320 | G>A,T | | intergenic_variant | IFI44 - ADGRL4 | 8e-06 | Tier 4: intronic/intergenic |
ClinVar germline variants
7 retrieved; paginated sample, class counts are floors:
2 pathogenic/likely pathogenic, 2 pathogenic, 2 likely pathogenic, 1 uncertain significance
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|
| 267833 | 46;XY;t(6;12)(q14;q24);20p+dn | | Pathogenic | criteria provided, single submitter |
| 16340 | NM_000142.5(FGFR3):c.749C>G (p.Pro250Arg) | FGFR3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 523570 | NM_207361.6(FREM2):c.6727C>T (p.Arg2243Ter) | FREM2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 997059 | GRCh37/hg19 Xp22.13-22.12(chrX:19183657-20215858) | SH3KBP1 | Pathogenic | criteria provided, single submitter |
| 691940 | NM_014681.6(DHX34):c.1322A>G (p.Asn441Ser) | DHX34 | Likely pathogenic | no assertion criteria provided |
| 586980 | NM_153332.4(ERI1):c.627del (p.Lys209_Val210insTer) | ERI1 | Likely pathogenic | criteria provided, single submitter |
| 1704348 | GRCh37/hg19 22q11.23(chr22:23652519-25059631)x3 | ADORA2A | Uncertain significance | no assertion criteria provided |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 73 · Orphanet: 43 · 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 |
|---|
| GREB1L | Definitive | Autosomal dominant | renal hypodysplasia/aplasia 3 | 10 |
| BMP4 | Supportive | Autosomal dominant | renal agenesis, unilateral | 10 |
| DSTYK | Supportive | Autosomal dominant | renal agenesis, unilateral | 8 |
| FRAS1 | Supportive | Autosomal dominant | renal agenesis, unilateral | 5 |
| FREM1 | Supportive | Autosomal dominant | renal agenesis, unilateral | 15 |
| FREM2 | Supportive | Autosomal dominant | renal agenesis, unilateral | 6 |
| RET | Supportive | Autosomal recessive | bilateral renal agenesis | 16 |
| UPK3A | Supportive | Autosomal dominant | renal agenesis, unilateral | 3 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|
| FREM2 | Orphanet:2052 | Fraser syndrome |
| FREM2 | Orphanet:93100 | Renal agenesis, unilateral |
| FREM2 | Orphanet:98949 | Complete cryptophthalmia |
| BMP4 | Orphanet:139471 | Microphthalmia with brain and digit anomalies |
| BMP4 | Orphanet:199306 | Cleft lip/palate |
| BMP4 | Orphanet:828 | Stickler syndrome |
| BMP4 | Orphanet:93100 | Renal agenesis, unilateral |
| UPK3A | Orphanet:93100 | Renal agenesis, unilateral |
| FRAS1 | Orphanet:2052 | Fraser syndrome |
| FRAS1 | Orphanet:93100 | Renal agenesis, unilateral |
| FREM1 | Orphanet:217266 | BNAR syndrome |
| FREM1 | Orphanet:2717 | Oculotrichoanal syndrome |
| FREM1 | Orphanet:3366 | Non-syndromic metopic craniosynostosis |
| FREM1 | Orphanet:93100 | Renal agenesis, unilateral |
| DSTYK | Orphanet:101003 | Autosomal recessive spastic paraplegia type 23 |
| DSTYK | Orphanet:93100 | Renal agenesis, unilateral |
| GREB1L | Orphanet:1848 | Renal agenesis, bilateral |
| GREB1L | Orphanet:93100 | Renal agenesis, unilateral |
| RET | Orphanet:146 | Differentiated thyroid carcinoma |
| RET | Orphanet:1848 | Renal agenesis, bilateral |
| RET | Orphanet:247698 | Multiple endocrine neoplasia type 2A |
| RET | Orphanet:247709 | Multiple endocrine neoplasia type 2B |
| RET | Orphanet:276621 | Sporadic pheochromocytoma/secreting paraganglioma |
| RET | Orphanet:29072 | Hereditary pheochromocytoma-paraganglioma |
| RET | Orphanet:388 | Hirschsprung disease |
| RET | Orphanet:93100 | Renal agenesis, unilateral |
| RET | Orphanet:99361 | Isolated familial medullary thyroid carcinoma |
| RET | Orphanet:99803 | Haddad syndrome |
| SH3KBP1 | Orphanet:696945 | X-linked common variable immunodeficiency phenotype due to SH3KBP1 deficiency |
| ADORA2A | Orphanet:363549 | Acute encephalopathy with biphasic seizures and late reduced diffusion |
| FGFR3 | Orphanet:15 | Achondroplasia |
| FGFR3 | Orphanet:1860 | Thanatophoric dysplasia type 1 |
| FGFR3 | Orphanet:2363 | Lacrimoauriculodentodigital syndrome |
| FGFR3 | Orphanet:251576 | Gliosarcoma |
| FGFR3 | Orphanet:251579 | Giant cell glioblastoma |
| FGFR3 | Orphanet:35099 | Non-syndromic bicoronal craniosynostosis |
| FGFR3 | Orphanet:429 | Hypochondroplasia |
| FGFR3 | Orphanet:53271 | Muenke syndrome |
| FGFR3 | Orphanet:794 | Saethre-Chotzen syndrome |
| FGFR3 | Orphanet:85164 | Camptodactyly-tall stature-scoliosis-hearing loss syndrome |
| FGFR3 | Orphanet:85165 | Severe achondroplasia-developmental delay-acanthosis nigricans syndrome |
| FGFR3 | Orphanet:93262 | Crouzon syndrome-acanthosis nigricans syndrome |
| FGFR3 | Orphanet:93274 | Thanatophoric dysplasia type 2 |
Cohort genes → proteins
13 cohort genes, 13 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|
| multi_evidence | 13 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|
| FREM2 | HGNC:25396 | ENSG00000150893 | Q5SZK8 | FRAS1-related extracellular matrix protein 2 | gencc,clinvar |
| BMP4 | HGNC:1071 | ENSG00000125378 | P12644 | Bone morphogenetic protein 4 | gencc |
| UPK3A | HGNC:12580 | ENSG00000100373 | O75631 | Uroplakin-3a | gencc |
| FRAS1 | HGNC:19185 | ENSG00000138759 | Q86XX4 | Extracellular matrix organizing protein FRAS1 | gencc |
| FREM1 | HGNC:23399 | ENSG00000164946 | Q5H8C1 | FRAS1-related extracellular matrix protein 1 | gencc |
| DSTYK | HGNC:29043 | ENSG00000133059 | Q6XUX3 | Dual serine/threonine and tyrosine protein kinase | gencc |
| GREB1L | HGNC:31042 | ENSG00000141449 | Q9C091 | GREB1-like protein | gencc |
| RET | HGNC:9967 | ENSG00000165731 | P07949 | Proto-oncogene tyrosine-protein kinase receptor Ret | gencc |
| SH3KBP1 | HGNC:13867 | ENSG00000147010 | Q96B97 | SH3 domain-containing kinase-binding protein 1 | clinvar |
| DHX34 | HGNC:16719 | ENSG00000134815 | Q14147 | Probable ATP-dependent RNA helicase DHX34 | clinvar |
| ERI1 | HGNC:23994 | ENSG00000104626 | Q8IV48 | 3’-5’ exoribonuclease 1 | clinvar |
| ADORA2A | HGNC:263 | ENSG00000128271 | P29274 | Adenosine receptor A2a | clinvar |
| FGFR3 | HGNC:3690 | ENSG00000068078 | P22607 | Fibroblast growth factor receptor 3 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|
| FREM2 | FRAS1-related extracellular matrix protein 2 | Extracellular matrix protein required for maintenance of the integrity of the skin epithelium and for maintenance of renal epithelia. |
| BMP4 | Bone morphogenetic protein 4 | Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including neurogenesis, vascular development, angiogenesis and osteogenesis. |
| UPK3A | Uroplakin-3a | Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells. |
| FRAS1 | Extracellular matrix organizing protein FRAS1 | Involved in extracellular matrix organization. |
| FREM1 | FRAS1-related extracellular matrix protein 1 | Extracellular matrix protein that plays a role in epidermal differentiation and is required for epidermal adhesion during embryonic development. |
| DSTYK | Dual serine/threonine and tyrosine protein kinase | Acts as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor-receptor activation. |
| GREB1L | GREB1-like protein | Plays a major role in early metanephros and genital development. |
| RET | Proto-oncogene tyrosine-protein kinase receptor Ret | Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN,… |
| SH3KBP1 | SH3 domain-containing kinase-binding protein 1 | Adapter protein involved in regulating diverse signal transduction pathways. |
| DHX34 | Probable ATP-dependent RNA helicase DHX34 | Probable ATP-binding RNA helicase required for nonsense-mediated decay (NMD) degradation of mRNA transcripts containing premature stop codons. |
| ERI1 | 3’-5’ exoribonuclease 1 | RNA exonuclease that binds to the 3’-end of histone mRNAs and degrades them, suggesting that it plays an essential role in histone mRNA decay after replication. |
| ADORA2A | Adenosine receptor A2a | Receptor for adenosine. |
| FGFR3 | Fibroblast growth factor receptor 3 | Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. |
Protein-family classification
Druggable: 4 · Difficult: 2 · Unknown: 7 · Druggable fraction: 0.31
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 |
|---|
| Kinase | 3 | 6.4× | 0.051 |
| GPCR | 1 | 1.8× | 0.813 |
| Scaffold/PPI | 1 | 1.3× | 0.813 |
| Other/Unknown | 7 | 1.0× | 0.813 |
| Transcription factor | 1 | 0.6× | 0.813 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|
| FREM2 | Other/Unknown | no | | Calx_beta, CalX-like_sf, CSPG_rpt |
| BMP4 | Other/Unknown | no | | TGF-b_propeptide, TGF-b_C, TGF-beta-like |
| UPK3A | Other/Unknown | no | | Uroplakin-3a, Uroplakin-3 |
| FRAS1 | Other/Unknown | no | | EGF, VWF_dom, Calx_beta |
| FREM1 | Other/Unknown | no | | C-type_lectin-like, Calx_beta, C-type_lectin-like/link_sf |
| DSTYK | Kinase | yes | | Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf |
| GREB1L | Other/Unknown | no | | GREB1, GREB1_N, GREB1-like_C |
| RET | Kinase | yes | 2.7.10.1 | Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Cadherin-like_dom |
| SH3KBP1 | Scaffold/PPI | no | | SH3_domain, CIN85_SH3_1, CIN85_SH3_2 |
| DHX34 | Transcription factor | no | 3.6.4.13 | Helicase_C-like, Helicase-assoc_dom, DEAD/DEAH_box_helicase_dom |
| ERI1 | Other/Unknown | no | | SAP_dom, RNaseH-like_sf, Ribonucl_H |
| ADORA2A | GPCR | yes | | GPCR_Rhodpsn, Adeno_A2A_rcpt, Adenosn_rcpt |
| FGFR3 | Kinase | yes | 2.7.10.1 | Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2 |
Expression context
Cohort genes with no expression data: 0.
12 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 13 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|
| kidney epithelium | 2 |
| renal medulla | 2 |
| gastrocnemius | 2 |
| secondary oocyte | 2 |
| adrenal tissue | 1 |
| pigmented layer of retina | 1 |
| rectum | 1 |
| retina | 1 |
| mucosa of urinary bladder | 1 |
| muscle of leg | 1 |
| germinal epithelium of ovary | 1 |
| parietal pleura | 1 |
| metanephros | 1 |
| smooth muscle tissue | 1 |
| lateral nuclear group of thalamus | 1 |
| medial globus pallidus | 1 |
| superior vestibular nucleus | 1 |
| buccal mucosa cell | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| dorsal root ganglion | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|
| FREM2 | 160 | broad | marker | adrenal tissue, kidney epithelium, renal medulla |
| BMP4 | 189 | ubiquitous | marker | pigmented layer of retina, retina, rectum |
| UPK3A | 126 | broad | marker | gastrocnemius, mucosa of urinary bladder, muscle of leg |
| FRAS1 | 212 | ubiquitous | marker | germinal epithelium of ovary, parietal pleura, renal medulla |
| FREM1 | 171 | broad | marker | kidney epithelium, smooth muscle tissue, metanephros |
| DSTYK | 287 | ubiquitous | marker | lateral nuclear group of thalamus, medial globus pallidus, superior vestibular nucleus |
| GREB1L | 184 | broad | marker | buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, gastrocnemius |
| RET | 193 | broad | marker | substantia nigra pars reticulata, dorsal root ganglion, substantia nigra pars compacta |
| SH3KBP1 | 254 | ubiquitous | marker | secondary oocyte, left ventricle myocardium, ileal mucosa |
| DHX34 | 217 | ubiquitous | marker | right testis, blood, left testis |
| ERI1 | 211 | ubiquitous | yes | secondary oocyte, primordial germ cell in gonad, oocyte |
| ADORA2A | 132 | broad | marker | putamen, caudate nucleus, nucleus accumbens |
| FGFR3 | 262 | broad | marker | upper leg skin, skin of hip, upper arm skin |
Protein interactions among cohort
Intra-cohort edges: 4.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|
| FGFR3 | 4,510 |
| BMP4 | 4,425 |
| RET | 4,203 |
| SH3KBP1 | 2,825 |
| FRAS1 | 2,552 |
| DHX34 | 2,501 |
| ADORA2A | 2,108 |
| FREM2 | 1,652 |
| FREM1 | 1,541 |
| DSTYK | 1,487 |
Intra-cohort edges
| A | B | Sources |
|---|
| FRAS1 | FREM1 | string_interaction |
| FRAS1 | FREM2 | string_interaction |
| FREM1 | FREM2 | intact, string_interaction |
| RET | UPK3A | string_interaction |
Structural data
PDB: 5 · AlphaFold-only: 8 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|
| ADORA2A | P29274 | 188 |
| RET | P07949 | 34 |
| FGFR3 | P22607 | 15 |
| SH3KBP1 | Q96B97 | 7 |
| ERI1 | Q8IV48 | 5 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|
| DSTYK | Q6XUX3 | 81.02 |
| DHX34 | Q14147 | 80.85 |
| BMP4 | P12644 | 79.12 |
| UPK3A | O75631 | 78.77 |
| FREM1 | Q5H8C1 | 75.75 |
| GREB1L | Q9C091 | 72.90 |
| FREM2 | Q5SZK8 | |
| FRAS1 | Q86XX4 | |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 75. Enrichment computed across 13 evidence-associated genes (6 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 6 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 nephric duct | 2 | 211.5× | 0.002 | BMP4, RET |
| Formation of the ureteric bud | 2 | 165.5× | 0.002 | BMP4, RET |
| Activation of TRKA receptors | 1 | 1903.3× | 0.008 | ADORA2A |
| t(4;14) translocations of FGFR3 | 1 | 1903.3× | 0.008 | FGFR3 |
| Signaling by FGFR3 fusions in cancer | 1 | 1903.3× | 0.008 | FGFR3 |
| Adenosine P1 receptors | 1 | 475.8× | 0.024 | ADORA2A |
| NGF-independant TRKA activation | 1 | 380.7× | 0.024 | ADORA2A |
| Formation of lateral plate mesoderm | 1 | 380.7× | 0.024 | BMP4 |
| Nucleotide-like (purinergic) receptors | 1 | 317.2× | 0.024 | ADORA2A |
| Reelin signalling pathway | 1 | 317.2× | 0.024 | SH3KBP1 |
| FGFR3b ligand binding and activation | 1 | 271.9× | 0.024 | FGFR3 |
| RAF/MAP kinase cascade | 2 | 20.4× | 0.024 | FGFR3, RET |
| Formation of intermediate mesoderm | 1 | 237.9× | 0.024 | BMP4 |
| Listeria monocytogenes entry into host cells | 1 | 173.0× | 0.027 | SH3KBP1 |
| Signaling by activated point mutants of FGFR3 | 1 | 158.6× | 0.027 | FGFR3 |
| FGFR3c ligand binding and activation | 1 | 146.4× | 0.027 | FGFR3 |
| Phospholipase C-mediated cascade; FGFR3 | 1 | 146.4× | 0.027 | FGFR3 |
| Specification of primordial germ cells | 1 | 146.4× | 0.027 | BMP4 |
| Signaling by Receptor Tyrosine Kinases | 2 | 17.2× | 0.027 | SH3KBP1, ADORA2A |
| Kidney development | 1 | 135.9× | 0.028 | BMP4 |
| InlB-mediated entry of Listeria monocytogenes into host cell | 1 | 126.9× | 0.028 | SH3KBP1 |
| Germ layer formation at gastrulation | 1 | 112.0× | 0.029 | BMP4 |
| PI-3K cascade:FGFR3 | 1 | 105.7× | 0.029 | FGFR3 |
| Specification of the neural plate border | 1 | 105.7× | 0.029 | BMP4 |
| SHC-mediated cascade:FGFR3 | 1 | 100.2× | 0.030 | FGFR3 |
| FRS-mediated FGFR3 signaling | 1 | 90.6× | 0.031 | FGFR3 |
| Negative regulation of MET activity | 1 | 86.5× | 0.031 | SH3KBP1 |
| Signaling by FGFR3 in disease | 1 | 82.8× | 0.031 | FGFR3 |
| NPAS4 regulates expression of target genes | 1 | 82.8× | 0.031 | RET |
| Negative regulation of FGFR3 signaling | 1 | 73.2× | 0.034 | FGFR3 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|
| cell communication | 3 | 194.4× | 1e-04 | FREM2, FRAS1, FREM1 |
| kidney development | 4 | 43.2× | 2e-04 | FREM2, BMP4, UPK3A, GREB1L |
| morphogenesis of an epithelium | 3 | 79.4× | 6e-04 | FREM2, FRAS1, GREB1L |
| positive regulation of ERK1 and ERK2 cascade | 4 | 26.2× | 8e-04 | BMP4, ADORA2A, DSTYK, FGFR3 |
| anatomical structure morphogenesis | 3 | 32.1× | 0.005 | FREM2, FRAS1, FREM1 |
| cardiac muscle cell differentiation | 2 | 103.7× | 0.008 | BMP4, GREB1L |
| positive regulation of circadian sleep/wake cycle, sleep | 1 | 1296.3× | 0.009 | ADORA2A |
| intermediate mesodermal cell differentiation | 1 | 1296.3× | 0.009 | BMP4 |
| negative regulation of developmental growth | 1 | 1296.3× | 0.009 | FGFR3 |
| positive regulation of cardiac muscle fiber development | 1 | 1296.3× | 0.009 | BMP4 |
| bronchus development | 1 | 1296.3× | 0.009 | BMP4 |
| bud dilation involved in lung branching | 1 | 1296.3× | 0.009 | BMP4 |
| mammary gland formation | 1 | 1296.3× | 0.009 | BMP4 |
| negative regulation of mesenchymal cell proliferation involved in ureter development | 1 | 1296.3× | 0.009 | BMP4 |
| negative regulation of glomerulus development | 1 | 1296.3× | 0.009 | BMP4 |
| regulation of mesodermal cell differentiation | 1 | 1296.3× | 0.009 | BMP4 |
| negative regulation of metanephric S-shaped body morphogenesis | 1 | 1296.3× | 0.009 | BMP4 |
| negative regulation of metanephric comma-shaped body morphogenesis | 1 | 1296.3× | 0.009 | BMP4 |
| endochondral ossification | 2 | 83.6× | 0.009 | BMP4, FGFR3 |
| metanephros development | 2 | 78.6× | 0.009 | BMP4, GREB1L |
| ureteric bud development | 2 | 70.1× | 0.009 | BMP4, RET |
| branching involved in ureteric bud morphogenesis | 2 | 56.4× | 0.009 | BMP4, GREB1L |
| chondrocyte differentiation | 2 | 46.3× | 0.009 | BMP4, FGFR3 |
| embryonic digit morphogenesis | 2 | 46.3× | 0.009 | FREM2, BMP4 |
| cell-cell signaling | 3 | 16.1× | 0.009 | SH3KBP1, ADORA2A, FGFR3 |
| embryonic epithelial tube formation | 1 | 648.1× | 0.013 | RET |
| posterior midgut development | 1 | 648.1× | 0.013 | RET |
| tendon cell differentiation | 1 | 648.1× | 0.013 | BMP4 |
| positive regulation of branching involved in lung morphogenesis | 1 | 648.1× | 0.013 | BMP4 |
| negative regulation of glomerular mesangial cell proliferation | 1 | 648.1× | 0.013 | BMP4 |
Therapeutics
Drug target analysis
Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 4 · Undrugged: 9
Druggability breadth: 5 of 13 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.
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|
| RET | 135 | 4 |
| ADORA2A | 81 | 4 |
| FGFR3 | 64 | 4 |
| DSTYK | 15 | 4 |
| FREM2 | 0 | 0 |
| BMP4 | 0 | 0 |
| UPK3A | 0 | 0 |
| FRAS1 | 0 | 0 |
| FREM1 | 0 | 0 |
| GREB1L | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|
| FEDRATINIB | 4 | ADORA2A, DSTYK, FGFR3, RET |
| NERATINIB | 4 | DSTYK |
| DABRAFENIB | 4 | DSTYK |
| BOSUTINIB | 4 | DSTYK, RET |
| SUNITINIB | 4 | ADORA2A, DSTYK, FGFR3, RET |
| CRIZOTINIB | 4 | DSTYK, FGFR3, RET |
| MIDOSTAURIN | 4 | DSTYK, FGFR3, RET |
| PONATINIB | 4 | FGFR3, RET |
| AFATINIB | 4 | RET |
| VEMURAFENIB | 4 | RET |
| TIVOZANIB | 4 | RET |
| LENVATINIB | 4 | FGFR3, RET |
| AXITINIB | 4 | FGFR3, RET |
| SORAFENIB | 4 | FGFR3, RET |
| DASATINIB ANHYDROUS | 4 | RET |
| ALECTINIB | 4 | RET |
| RUXOLITINIB | 4 | RET |
| INFIGRATINIB PHOSPHATE | 4 | FGFR3, RET |
| INFIGRATINIB | 4 | FGFR3, RET |
| IBRUTINIB | 4 | ADORA2A, RET |
| PALBOCICLIB | 4 | RET |
| REGORAFENIB | 4 | RET |
| ENTRECTINIB | 4 | FGFR3, RET |
| TOFACITINIB CITRATE | 4 | RET |
| FOSTAMATINIB | 4 | RET |
| CABOZANTINIB | 4 | RET |
| BARICITINIB | 4 | RET |
| TOFACITINIB | 4 | RET |
| CAPIVASERTIB | 4 | RET |
| CERITINIB | 4 | FGFR3, RET |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 3.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|
| ADORA2A | 1,679 | Binding:1372, Functional:301, ADMET:6 |
| RET | 1,586 | Binding:1573, Functional:10, ADMET:3 |
| FGFR3 | 975 | Binding:948, Functional:18, ADMET:9 |
| DSTYK | 90 | Binding:90 |
| BMP4 | 2 | Binding:2 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|
| RET | 2.7.10.1 | receptor protein-tyrosine kinase |
| DHX34 | 3.6.4.13 | RNA helicase |
| FGFR3 | 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 |
|---|
| RET | 1,586 |
| ADORA2A | 1,679 |
| FGFR3 | 975 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 13; 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) |
|---|
| FEDRATINIB | 4 | ADORA2A, DSTYK, FGFR3, RET |
| NERATINIB | 4 | DSTYK |
| DABRAFENIB | 4 | DSTYK |
| BOSUTINIB | 4 | DSTYK, RET |
| SUNITINIB | 4 | ADORA2A, DSTYK, FGFR3, RET |
| CRIZOTINIB | 4 | DSTYK, FGFR3, RET |
| MIDOSTAURIN | 4 | DSTYK, FGFR3, RET |
| PONATINIB | 4 | FGFR3, RET |
| AFATINIB | 4 | RET |
| VEMURAFENIB | 4 | RET |
| TIVOZANIB | 4 | RET |
| LENVATINIB | 4 | FGFR3, RET |
| AXITINIB | 4 | FGFR3, RET |
| SORAFENIB | 4 | FGFR3, RET |
| DASATINIB ANHYDROUS | 4 | RET |
| ALECTINIB | 4 | RET |
| RUXOLITINIB | 4 | RET |
| INFIGRATINIB PHOSPHATE | 4 | FGFR3, RET |
| INFIGRATINIB | 4 | FGFR3, RET |
| IBRUTINIB | 4 | ADORA2A, RET |
| PALBOCICLIB | 4 | RET |
| REGORAFENIB | 4 | RET |
| ENTRECTINIB | 4 | FGFR3, RET |
| TOFACITINIB CITRATE | 4 | RET |
| FOSTAMATINIB | 4 | RET |
| CABOZANTINIB | 4 | RET |
| BARICITINIB | 4 | RET |
| TOFACITINIB | 4 | RET |
| CAPIVASERTIB | 4 | RET |
| CERITINIB | 4 | FGFR3, RET |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|
| A | Approved (phase 4 drug) | 4 | DSTYK, RET, ADORA2A, FGFR3 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 9 | FREM2, BMP4, UPK3A, FRAS1, FREM1, GREB1L, SH3KBP1, DHX34, ERI1 |
Undrugged target profiles
9 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|
| FREM2 | 0 | — |
| BMP4 | 2 | — |
| UPK3A | 0 | — |
| FRAS1 | 0 | — |
| FREM1 | 0 | — |
| GREB1L | 0 | — |
| SH3KBP1 | 0 | — |
| DHX34 | 0 | — |
| ERI1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 1.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|
| NCT01831141 | Not specified | UNKNOWN | Long Term Outcome of Congenital Solitary Kidney |
- Cohort genes: FREM2, BMP4, UPK3A, FRAS1, FREM1, DSTYK, GREB1L, RET, SH3KBP1, DHX34, ERI1, ADORA2A, FGFR3