Fraser syndrome 3
diseaseOn this page
Also known as FRASRS3
Summary
Fraser syndrome 3 (MONDO:0054739) is a disease caused by GRIP1 (GenCC Strong), with 17 cohort genes.
At a glance
- Causal gene: GRIP1 (GenCC Strong)
- Cohort genes: 17
- ClinVar variants: 221
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Fraser syndrome 3 |
| Mondo ID | MONDO:0054739 |
| OMIM | 617667 |
| DOID | DOID:0111406 |
| UMLS | C4540040 |
| MedGen | 1621907 |
| GARD | 0025964 |
| Is cancer (heuristic) | no |
Also known as: Fraser syndrome 3 · FRASRS3
Data availability: 221 ClinVar variants · 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › syndromic disease › Fraser syndrome › Fraser syndrome 3
Related subtypes (2): Fraser syndrome 1, Fraser syndrome 2
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
221 retrieved; paginated sample, class counts are floors:
155 uncertain significance, 23 conflicting classifications of pathogenicity, 12 likely benign, 10 benign, 9 benign/likely benign, 8 likely pathogenic, 3 pathogenic, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 36970 | NM_001366722.1(GRIP1):c.2269+1G>C | GRIP1 | Pathogenic | no assertion criteria provided |
| 36971 | NM_001366722.1(GRIP1):c.1337_1340del (p.Lys446fs) | GRIP1 | Pathogenic | no assertion criteria provided |
| 620314 | NM_001366722.1(GRIP1):c.30T>A (p.Cys10Ter) | GRIP1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 974698 | NM_001366722.1(GRIP1):c.1930C>T (p.Gln644Ter) | GRIP1 | Pathogenic | no assertion criteria provided |
| 2802784 | NM_001366722.1(GRIP1):c.1199-2del | GRIP1 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3575200 | NM_021150.4(GRIP1):c.1618_1619insTATATCTCCATTATTACAGCACCAT | GRIP1 | Likely pathogenic | criteria provided, single submitter |
| 3575202 | NM_001366722.1(GRIP1):c.1688-1G>C | GRIP1 | Likely pathogenic | criteria provided, single submitter |
| 3575209 | NM_001366722.1(GRIP1):c.1285del (p.Leu429fs) | GRIP1 | Likely pathogenic | criteria provided, single submitter |
| 3575210 | NM_001366722.1(GRIP1):c.1279C>T (p.Arg427Ter) | GRIP1 | Likely pathogenic | criteria provided, single submitter |
| 3575215 | NM_001366722.1(GRIP1):c.1199-2A>G | GRIP1 | Likely pathogenic | criteria provided, single submitter |
| 3575234 | NM_001366722.1(GRIP1):c.206C>A (p.Ser69Ter) | GRIP1 | Likely pathogenic | criteria provided, single submitter |
| 3575236 | NM_001366722.1(GRIP1):c.116_117del (p.Val39fs) | GRIP1 | Likely pathogenic | criteria provided, single submitter |
| 974703 | NM_000049.4(ASPA):c.806C>T (p.Thr269Met) | ASPA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1698650 | NM_001366722.1(GRIP1):c.386T>C (p.Val129Ala) | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 227419 | NM_001366722.1(GRIP1):c.2381T>G (p.Met794Arg) | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2540277 | NM_001366722.1(GRIP1):c.2393C>T (p.Thr798Met) | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 265191 | NM_001366722.1(GRIP1):c.1756A>C (p.Ile586Leu) | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2794528 | NM_001366722.1(GRIP1):c.1710A>T (p.Gly570=) | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2838552 | NM_001366722.1(GRIP1):c.419-11C>T | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2978523 | NM_001366722.1(GRIP1):c.43C>T (p.Arg15Ter) | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 310298 | NM_001366722.1(GRIP1):c.3048T>C (p.Phe1016=) | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 310301 | NM_001366722.1(GRIP1):c.2793G>A (p.Ser931=) | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 310311 | NM_001366722.1(GRIP1):c.872+7A>G | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 310313 | NM_001366722.1(GRIP1):c.345C>T (p.Asp115=) | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 310315 | NM_001366722.1(GRIP1):c.240A>G (p.Val80=) | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 381678 | NM_001366722.1(GRIP1):c.1645A>G (p.Ile549Val) | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 402210 | NM_001366722.1(GRIP1):c.160G>A (p.Val54Ile) | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 754761 | NM_001366722.1(GRIP1):c.1428G>A (p.Thr476=) | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 755754 | NM_001366722.1(GRIP1):c.1688-6T>C | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 881655 | NM_001366722.1(GRIP1):c.3223G>A (p.Gly1075Arg) | GRIP1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 8 · Orphanet: 22 · 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 |
|---|---|---|---|---|
| GRIP1 | Strong | Autosomal recessive | Fraser syndrome 3 | 4 |
| NCOA2 | Strong | Autosomal recessive | Fraser syndrome 3 | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| GRIP1 | Orphanet:2052 | Fraser syndrome |
| MYO18B | Orphanet:447974 | Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome |
| MPC1 | Orphanet:447784 | Mitochondrial pyruvate carrier deficiency |
| MED23 | Orphanet:88616 | Autosomal recessive non-syndromic intellectual disability |
| ODAD1 | Orphanet:244 | Primary ciliary dyskinesia |
| WDR81 | Orphanet:1766 | Dysequilibrium syndrome |
| WDR81 | Orphanet:269505 | Congenital communicating hydrocephalus |
| WDR81 | Orphanet:269510 | Congenital non-communicating hydrocephalus |
| AIPL1 | Orphanet:1872 | Cone rod dystrophy |
| AIPL1 | Orphanet:65 | Leber congenital amaurosis |
| GNB5 | Orphanet:542306 | GNB5-related intellectual disability-cardiac arrhythmia syndrome |
| ASPA | Orphanet:314911 | Severe Canavan disease |
| ASPA | Orphanet:314918 | Mild Canavan disease |
| PTCH1 | Orphanet:220386 | Semilobar holoprosencephaly |
| PTCH1 | Orphanet:2353 | Schilbach-Rott syndrome |
| PTCH1 | Orphanet:280195 | Septopreoptic holoprosencephaly |
| PTCH1 | Orphanet:280200 | Microform holoprosencephaly |
| PTCH1 | Orphanet:377 | Gorlin syndrome |
| PTCH1 | Orphanet:77301 | Monosomy 9q22.3 syndrome |
| PTCH1 | Orphanet:93924 | Lobar holoprosencephaly |
| PTCH1 | Orphanet:93925 | Alobar holoprosencephaly |
| PTCH1 | Orphanet:93926 | Midline interhemispheric variant of holoprosencephaly |
Cohort genes → proteins
17 cohort genes, 17 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 17 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| GRIP1 | HGNC:18708 | ENSG00000155974 | Q9Y3R0 | Glutamate receptor-interacting protein 1 | gencc,clinvar |
| NCOA2 | HGNC:7669 | ENSG00000140396 | Q15596 | Nuclear receptor coactivator 2 | gencc,clinvar |
| ZXDA | HGNC:13198 | ENSG00000198205 | P98168 | Zinc finger X-linked protein ZXDA | clinvar |
| ADAMTS14 | HGNC:14899 | ENSG00000138316 | Q8WXS8 | A disintegrin and metalloproteinase with thrombospondin motifs 14 | clinvar |
| BCLAF1 | HGNC:16863 | ENSG00000029363 | Q9NYF8 | Bcl-2-associated transcription factor 1 | clinvar |
| LSM10 | HGNC:17562 | ENSG00000181817 | Q969L4 | U7 snRNA-associated Sm-like protein LSm10 | clinvar |
| MYO18B | HGNC:18150 | ENSG00000133454 | Q8IUG5 | Unconventional myosin-XVIIIb | clinvar |
| MPC1 | HGNC:21606 | ENSG00000060762 | Q9Y5U8 | Mitochondrial pyruvate carrier 1 | clinvar |
| MED23 | HGNC:2372 | ENSG00000112282 | Q9ULK4 | Mediator of RNA polymerase II transcription subunit 23 | clinvar |
| BORCS6 | HGNC:25939 | ENSG00000196544 | Q96GS4 | BLOC-1-related complex subunit 6 | clinvar |
| ODAD1 | HGNC:26560 | ENSG00000105479 | Q96M63 | Outer dynein arm-docking complex subunit 1 | clinvar |
| WDR81 | HGNC:26600 | ENSG00000167716 | Q562E7 | WD repeat-containing protein 81 | clinvar |
| TLCD3A | HGNC:29646 | ENSG00000167695 | Q8TBR7 | TLC domain-containing protein 3A | clinvar |
| AIPL1 | HGNC:359 | ENSG00000129221 | Q9NZN9 | Aryl-hydrocarbon-interacting protein-like 1 | clinvar |
| GNB5 | HGNC:4401 | ENSG00000069966 | O14775 | Guanine nucleotide-binding protein subunit beta-5 | clinvar |
| ASPA | HGNC:756 | ENSG00000108381 | P45381 | Aspartoacylase | clinvar |
| PTCH1 | HGNC:9585 | ENSG00000185920 | Q13635 | Protein patched homolog 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| GRIP1 | Glutamate receptor-interacting protein 1 | May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons. |
| NCOA2 | Nuclear receptor coactivator 2 | Transcriptional coactivator for steroid receptors and nuclear receptors. |
| ZXDA | Zinc finger X-linked protein ZXDA | Cooperates with CIITA to promote transcription of MHC class I and MHC class II genes. |
| ADAMTS14 | A disintegrin and metalloproteinase with thrombospondin motifs 14 | Has aminoprocollagen type I processing activity in the absence of ADAMTS2. |
| BCLAF1 | Bcl-2-associated transcription factor 1 | Death-promoting transcriptional repressor. |
| LSM10 | U7 snRNA-associated Sm-like protein LSm10 | Appears to function in the U7 snRNP complex that is involved in histone 3’-end processing. |
| MYO18B | Unconventional myosin-XVIIIb | May be involved in intracellular trafficking of the muscle cell when in the cytoplasm, whereas entering the nucleus, may be involved in the regulation of muscle specific genes. |
| MPC1 | Mitochondrial pyruvate carrier 1 | Mediates the uptake of pyruvate into mitochondria to maintain the balance between glycolysis and oxidative phosphorylation. |
| MED23 | Mediator of RNA polymerase II transcription subunit 23 | Required for transcriptional activation subsequent to the assembly of the pre-initiation complex. |
| BORCS6 | BLOC-1-related complex subunit 6 | As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. |
| ODAD1 | Outer dynein arm-docking complex subunit 1 | Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule. |
| WDR81 | WD repeat-containing protein 81 | Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. |
| AIPL1 | Aryl-hydrocarbon-interacting protein-like 1 | May be important in protein trafficking and/or protein folding and stabilization. |
| GNB5 | Guanine nucleotide-binding protein subunit beta-5 | Enhances GTPase-activating protein (GAP) activity of regulator of G protein signaling (RGS) proteins, such as RGS7 and RGS9, hence involved in the termination of the signaling initiated by the G protein coupled receptors (GPCRs) by acceler… |
| ASPA | Aspartoacylase | Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate. |
| PTCH1 | Protein patched homolog 1 | Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH). |
Protein-family classification
Druggable: 3 · Difficult: 4 · Unknown: 10 · Druggable fraction: 0.18
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 |
|---|---|---|---|
| Protease | 1 | 2.1× | 0.753 |
| Scaffold/PPI | 2 | 2.0× | 0.753 |
| Kinase | 1 | 1.6× | 0.753 |
| Other/Unknown | 10 | 1.1× | 0.753 |
| Transcription factor | 2 | 1.0× | 0.753 |
| Enzyme (other) | 1 | 0.7× | 0.773 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| GRIP1 | Scaffold/PPI | no | PDZ, PDZ_sf, PDZ_6 | |
| NCOA2 | Transcription factor | no | PAS, Nuc_rcpt_coact, NCO_DUF1518 | |
| ZXDA | Transcription factor | no | Znf_C2H2_type, Znf_C2H2_sf, | |
| ADAMTS14 | Protease | yes | 3.4.24.14 | TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N |
| BCLAF1 | Other/Unknown | no | THRAP3_BCLAF1 | |
| LSM10 | Other/Unknown | no | Sm_dom_euk/arc, LSM_dom_sf, Sm | |
| MYO18B | Other/Unknown | no | Myosin_head_motor_dom-like, P-loop_NTPase, MYSc_Myo18 | |
| MPC1 | Other/Unknown | no | MPC | |
| MED23 | Other/Unknown | no | Mediator_Med23 | |
| BORCS6 | Other/Unknown | no | BORCS6, BORCS6_C | |
| ODAD1 | Other/Unknown | no | ODAD1_CC, ODA-DC/CCD | |
| WDR81 | Kinase | yes | BEACH_dom, WD40_rpt, Kinase-like_dom_sf | |
| TLCD3A | Other/Unknown | no | TLC-dom, TLCD | |
| AIPL1 | Other/Unknown | no | TPR-like_helical_dom_sf, TPR_rpt, AIP/AIPL1/TTC9 | |
| GNB5 | Scaffold/PPI | no | WD40_G-protein_beta-like, WD40_rpt, WD40/YVTN_repeat-like_dom_sf | |
| ASPA | Enzyme (other) | yes | 3.5.1.15 | Aste_AspA_hybrid_dom, Aspartoacylase, AspA/AstE_fam |
| PTCH1 | Other/Unknown | no | SSD, TM_rcpt_patched, HMGCR/SNAP/NPC1-like_SSD |
Expression context
Cohort genes with no expression data: 0.
13 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) | 17 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| endothelial cell | 3 |
| granulocyte | 3 |
| buccal mucosa cell | 2 |
| calcaneal tendon | 2 |
| tibia | 2 |
| gastrocnemius | 2 |
| hindlimb stylopod muscle | 2 |
| cerebellar hemisphere | 2 |
| cortical plate | 1 |
| ganglionic eminence | 1 |
| ventricular zone | 1 |
| corpus epididymis | 1 |
| secondary oocyte | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| gall bladder | 1 |
| mucosa of transverse colon | 1 |
| vena cava | 1 |
| embryo | 1 |
| apex of heart | 1 |
| cardiac ventricle | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| GRIP1 | 192 | broad | marker | cortical plate, ganglionic eminence, ventricular zone |
| NCOA2 | 292 | ubiquitous | marker | corpus epididymis, endothelial cell, secondary oocyte |
| ZXDA | 208 | tissue_specific | yes | endothelial cell, buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis |
| ADAMTS14 | 156 | broad | yes | gall bladder, vena cava, mucosa of transverse colon |
| BCLAF1 | 295 | ubiquitous | marker | calcaneal tendon, tibia, embryo |
| LSM10 | 245 | ubiquitous | marker | hindlimb stylopod muscle, gastrocnemius, granulocyte |
| MYO18B | 148 | broad | marker | apex of heart, gastrocnemius, hindlimb stylopod muscle |
| MPC1 | 288 | ubiquitous | marker | heart right ventricle, cardiac ventricle, heart left ventricle |
| MED23 | 283 | ubiquitous | yes | right hemisphere of cerebellum, calcaneal tendon, cerebellar hemisphere |
| BORCS6 | 219 | ubiquitous | yes | type B pancreatic cell, olfactory bulb, granulocyte |
| ODAD1 | 174 | broad | marker | oviduct epithelium, right uterine tube, bronchial epithelial cell |
| WDR81 | 138 | ubiquitous | marker | granulocyte, left ovary, right ovary |
| TLCD3A | 228 | ubiquitous | marker | skin of abdomen, skin of leg, zone of skin |
| AIPL1 | 62 | tissue_specific | marker | buccal mucosa cell, pancreatic ductal cell, tendon of biceps brachii |
| GNB5 | 279 | ubiquitous | marker | middle temporal gyrus, endothelial cell, cerebellar hemisphere |
| ASPA | 238 | broad | marker | corpus callosum, nephron tubule, medial globus pallidus |
| PTCH1 | 275 | ubiquitous | marker | tibia, dorsal root ganglion, trigeminal ganglion |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| BCLAF1 | 4,230 |
| GRIP1 | 3,602 |
| PTCH1 | 3,368 |
| GNB5 | 2,987 |
| NCOA2 | 2,464 |
| MED23 | 2,155 |
| MYO18B | 1,775 |
| LSM10 | 1,724 |
| WDR81 | 1,404 |
| ODAD1 | 1,224 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| MED23 | NCOA2 | intact |
Structural data
PDB: 11 · AlphaFold-only: 6 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| NCOA2 | Q15596 | 381 |
| GNB5 | O14775 | 32 |
| PTCH1 | Q13635 | 16 |
| MPC1 | Q9Y5U8 | 13 |
| MED23 | Q9ULK4 | 13 |
| ASPA | P45381 | 8 |
| AIPL1 | Q9NZN9 | 6 |
| LSM10 | Q969L4 | 5 |
| BCLAF1 | Q9NYF8 | 2 |
| GRIP1 | Q9Y3R0 | 1 |
| ODAD1 | Q96M63 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| TLCD3A | Q8TBR7 | 92.98 |
| ADAMTS14 | Q8WXS8 | 70.22 |
| WDR81 | Q562E7 | 69.23 |
| BORCS6 | Q96GS4 | 66.53 |
| MYO18B | Q8IUG5 | 60.66 |
| ZXDA | P98168 | 55.14 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 117. Enrichment computed across 17 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes | 2 | 43.1× | 0.049 | NCOA2, MED23 |
| Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | 2 | 39.4× | 0.049 | NCOA2, MED23 |
| Adipogenesis | 2 | 31.3× | 0.049 | NCOA2, MED23 |
| Epigenetic regulation by WDR5-containing histone modifying complexes | 2 | 30.9× | 0.049 | NCOA2, MED23 |
| Regulation of lipid metabolism by PPARalpha | 2 | 28.2× | 0.049 | NCOA2, MED23 |
| Transcriptional regulation of white adipocyte differentiation | 2 | 25.9× | 0.049 | NCOA2, MED23 |
| GLI proteins bind promoters of Hh responsive genes to promote transcription | 1 | 163.1× | 0.067 | PTCH1 |
| Ligand-receptor interactions | 1 | 142.8× | 0.067 | PTCH1 |
| SLBP independent Processing of Histone Pre-mRNAs | 1 | 114.2× | 0.067 | LSM10 |
| Processing of Capped Intronless Pre-mRNA | 1 | 103.8× | 0.067 | LSM10 |
| SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs | 1 | 103.8× | 0.067 | LSM10 |
| Aspartate and asparagine metabolism | 1 | 103.8× | 0.067 | ASPA |
| Synthesis of bile acids and bile salts via 27-hydroxycholesterol | 1 | 76.1× | 0.067 | NCOA2 |
| R-HSA-1368082 | 1 | 71.4× | 0.067 | NCOA2 |
| Cytochrome P450 - arranged by substrate type | 1 | 71.4× | 0.067 | NCOA2 |
| Trafficking of GluR2-containing AMPA receptors | 1 | 67.2× | 0.067 | GRIP1 |
| Activation of SMO | 1 | 63.4× | 0.067 | PTCH1 |
| G beta:gamma signalling through BTK | 1 | 63.4× | 0.067 | GNB5 |
| Recycling of bile acids and salts | 1 | 60.1× | 0.067 | NCOA2 |
| Prostacyclin signalling through prostacyclin receptor | 1 | 60.1× | 0.067 | GNB5 |
| G beta:gamma signalling through PLC beta | 1 | 57.1× | 0.067 | GNB5 |
| G beta:gamma signalling through CDC42 | 1 | 57.1× | 0.067 | GNB5 |
| Presynaptic function of Kainate receptors | 1 | 54.4× | 0.067 | GNB5 |
| Bile acid and bile salt metabolism | 1 | 49.6× | 0.067 | NCOA2 |
| ADP signalling through P2Y purinoceptor 12 | 1 | 49.6× | 0.067 | GNB5 |
| G-protein activation | 1 | 47.6× | 0.067 | GNB5 |
| Thromboxane signalling through TP receptor | 1 | 47.6× | 0.067 | GNB5 |
| Collagen formation | 1 | 45.7× | 0.067 | ADAMTS14 |
| Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol | 1 | 45.7× | 0.067 | NCOA2 |
| ADP signalling through P2Y purinoceptor 1 | 1 | 45.7× | 0.067 | GNB5 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 17 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| acetate metabolic process | 1 | 991.3× | 0.033 | ASPA |
| response to chlorate | 1 | 495.6× | 0.033 | PTCH1 |
| neural plate axis specification | 1 | 495.6× | 0.033 | PTCH1 |
| cell proliferation involved in metanephros development | 1 | 495.6× | 0.033 | PTCH1 |
| dark adaptation | 1 | 495.6× | 0.033 | GNB5 |
| positive regulation of T cell extravasation | 1 | 495.6× | 0.033 | MED23 |
| pyruvate import into mitochondria | 1 | 330.4× | 0.033 | MPC1 |
| protein farnesylation | 1 | 330.4× | 0.033 | AIPL1 |
| light adaption | 1 | 330.4× | 0.033 | GNB5 |
| cell differentiation involved in kidney development | 1 | 330.4× | 0.033 | PTCH1 |
| negative regulation of smoothened signaling pathway | 2 | 53.6× | 0.033 | NCOA2, PTCH1 |
| cellular response to Thyroglobulin triiodothyronine | 1 | 247.8× | 0.040 | NCOA2 |
| epidermal cell fate specification | 1 | 198.3× | 0.041 | PTCH1 |
| mRNA 3’-end processing by stem-loop binding and cleavage | 1 | 165.2× | 0.041 | LSM10 |
| neural tube patterning | 1 | 165.2× | 0.041 | PTCH1 |
| hindlimb morphogenesis | 1 | 165.2× | 0.041 | PTCH1 |
| negative regulation of cell division | 1 | 141.6× | 0.041 | PTCH1 |
| mammary gland duct morphogenesis | 1 | 141.6× | 0.041 | PTCH1 |
| aspartate metabolic process | 1 | 123.9× | 0.041 | ASPA |
| positive regulation of epidermal cell differentiation | 1 | 123.9× | 0.041 | PTCH1 |
| positive regulation of neuron projection arborization | 1 | 123.9× | 0.041 | GRIP1 |
| G protein-coupled dopamine receptor signaling pathway | 1 | 110.1× | 0.041 | GNB5 |
| regulation of lysosome size | 1 | 110.1× | 0.041 | BORCS6 |
| neurotransmitter receptor transport, endosome to postsynaptic membrane | 1 | 110.1× | 0.041 | GRIP1 |
| positive regulation of DNA-templated transcription initiation | 1 | 110.1× | 0.041 | BCLAF1 |
| regulation of opsin-mediated signaling pathway | 1 | 99.1× | 0.041 | AIPL1 |
| aggrephagy | 1 | 99.1× | 0.041 | WDR81 |
| metanephric collecting duct development | 1 | 99.1× | 0.041 | PTCH1 |
| peroxisome proliferator activated receptor signaling pathway | 1 | 90.1× | 0.041 | NCOA2 |
| response to alkaloid | 1 | 90.1× | 0.041 | PTCH1 |
Therapeutics
Drug target analysis
Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 14
Druggability breadth: 5 of 17 evidence-associated genes (29%) 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 |
|---|---|
| NCOA2 | METHYLENE BLUE ANHYDROUS |
| MED23 | PALBOCICLIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| NCOA2 | 1 | 4 |
| BCLAF1 | 1 | 2 |
| MED23 | 1 | 4 |
| GRIP1 | 0 | 0 |
| ZXDA | 0 | 0 |
| ADAMTS14 | 0 | 0 |
| LSM10 | 0 | 0 |
| MYO18B | 0 | 0 |
| MPC1 | 0 | 0 |
| BORCS6 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| METHYLENE BLUE ANHYDROUS | 4 | NCOA2 |
| PALBOCICLIB | 4 | MED23 |
| MOLIBRESIB | 2 | BCLAF1 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 2.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| MED23 | 9 | Binding:9 |
| BCLAF1 | 8 | Binding:8 |
| PTCH1 | 4 | Binding:4 |
| NCOA2 | 3 | Functional:2, Binding:1 |
| AIPL1 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| ADAMTS14 | 3.4.24.14 | procollagen N-endopeptidase |
| ASPA | 3.5.1.15 | aspartoacylase |
Pharmacogenomics
Cohort genes with a PharmGKB record: 17; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
3 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) |
|---|---|---|
| METHYLENE BLUE ANHYDROUS | 4 | NCOA2 |
| PALBOCICLIB | 4 | MED23 |
| MOLIBRESIB | 2 | BCLAF1 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | NCOA2, MED23 |
| B | Phased (≥1) drug, not yet approved | 1 | BCLAF1 |
| C | Druggable family + PDB, no drug | 1 | ASPA |
| D | Druggable family + AlphaFold only, no drug | 2 | ADAMTS14, WDR81 |
| E | Difficult family or no structure, no drug | 11 | GRIP1, ZXDA, LSM10, MYO18B, MPC1, BORCS6, ODAD1, TLCD3A, AIPL1, GNB5 (+1 more) |
Undrugged target profiles
14 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| GRIP1 | 0 | — |
| ZXDA | 0 | — |
| ADAMTS14 | 0 | — |
| LSM10 | 0 | — |
| MYO18B | 0 | — |
| MPC1 | 0 | — |
| BORCS6 | 0 | — |
| ODAD1 | 0 | — |
| WDR81 | 0 | — |
| TLCD3A | 0 | — |
| AIPL1 | 1 | — |
| GNB5 | 0 | — |
| ASPA | 0 | — |
| PTCH1 | 4 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.