Pit and fissure surface dental caries
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Summary
Pit and fissure surface dental caries (MONDO:0005591) is a disease with 15 cohort genes (22 GWAS associations across 2 studies).
At a glance
- Cohort genes: 15
- GWAS associations: 22
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | pit and fissure surface dental caries |
| Mondo ID | MONDO:0005591 |
| UMLS | C1290627 |
| MedGen | 712983 |
| Is cancer (heuristic) | no |
Data availability: 22 GWAS associations (2 studies).
Disease family
Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › tooth disorder › tooth hard tissue disease › dental caries › pit and fissure surface dental caries
Related subtypes (4): dentin caries, odontoclasia, enamel caries, smooth surface dental caries
Genetics & variants
GWAS landscape
22 GWAS associations across 2 studies. Top hits map to 10 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| rs17236529 | 2e-09 | KPNA4 | T | 1.78 |
| rs17145638 | 2e-07 | LINC03053 - BCOR | C | 2.33 |
| rs6560397 | 2e-07 | PIP5K1B | T | 1.29 |
| rs11082098 | 3e-07 | RPL12P40 - RN7SKP182 | A | 1.03 |
| rs2046315 | 7e-07 | RLIG1P3 - RPSAP74 | T | 1.87 |
| rs5967638 | 1e-06 | MIR1321 - SFR1P2 | A | 2.02 |
| rs9788927 | 2e-06 | RBFOX1 - LINC02152 | A | 1.02 |
| rs17736906 | 2e-06 | HAUS6P3 - LINC02854 | A | 0.74 |
| rs13273891 | 2e-06 | FAM110B | A | 0.95 |
| rs12850804 | 2e-06 | LARP1BP3 - CCDC160 | T | 0.75 |
| rs10958998 | 4e-06 | PTPRD | A | 1.19 |
| rs11822667 | 4e-06 | RN7SKP279 - DNAJB6P1 | A | 1.66 |
| rs12542759 | 4e-06 | EFR3A - OC90 | T | 0.8 |
| rs758569 | 4e-06 | PDZD8 - EMX2OS | A | 0.8 |
| rs197480 | 4e-06 | ADGRG6 - HIVEP2 | T | 1.43 |
| rs9311745 | 5e-06 | FHIT | C | 2.99 |
| rs9504361 | 6e-06 | EXOC2 | G | 1.16 |
| rs6806253 | 6e-06 | GATA2-AS1 - LINC01565 | A | 1.56 |
| rs2022068 | 7e-06 | PVALB | A | 1.18 |
| rs10486722 | 7e-06 | INHBA-AS1 | C | 1.22 |
| rs7121800 | 7e-06 | MPPED2 | T | 0.71 |
| rs17013524 | 9e-06 | CNTN4 | T | 1.83 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST002358 | Zeng Z | 2014 | 0 | 0 | Genome-wide association study of primary dentition pit-and-fissure and smooth surface caries. |
| GCST001897 | Zeng Z | 2013 | 0 | 0 | Genome-wide association studies of pit-and-fissure- and smooth-surface caries in permanent dentition. |
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 | 22 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 18 |
| low_freq (0.01-0.05) | 4 |
| rare (<0.01) | 0 |
| unknown | 0 |
Functional consequences
| Consequence | Count |
|---|---|
| intron_variant | 13 |
| intergenic_variant | 8 |
| non_coding_transcript_exon_variant | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| rs17236529 | 3 | 160508519 | C>T | 0.034 | intron_variant | KPNA4 | 2e-09 | Tier 4: intronic/intergenic |
| rs17145638 | X | 40026377 | T>C | 0.117 | intergenic_variant | LINC03053 - BCOR | 2e-07 | Tier 4: intronic/intergenic |
| rs6560397 | 9 | 68856996 | C>G,T | 0.467 | intron_variant | PIP5K1B | 2e-07 | Tier 4: intronic/intergenic |
| rs11082098 | 18 | 38618768 | C>A | 0.056 | intergenic_variant | RPL12P40 - RN7SKP182 | 3e-07 | Tier 4: intronic/intergenic |
| rs2046315 | 8 | 89198871 | A>C,G,T | 0.132 | intergenic_variant | RLIG1P3 - RPSAP74 | 7e-07 | Tier 4: intronic/intergenic |
| rs5967638 | X | 85840734 | G>A | 0.067 | intergenic_variant | MIR1321 - SFR1P2 | 1e-06 | Tier 4: intronic/intergenic |
| rs9788927 | 16 | 7879826 | A>C,T | 0.148 | intron_variant | RBFOX1 - LINC02152 | 2e-06 | Tier 4: intronic/intergenic |
| rs17736906 | 7 | 53914933 | A>C,G | 0.156 | intergenic_variant | HAUS6P3 - LINC02854 | 2e-06 | Tier 4: intronic/intergenic |
| rs13273891 | 8 | 58073900 | G>A | 0.193 | intron_variant | FAM110B | 2e-06 | Tier 4: intronic/intergenic |
| rs12850804 | X | 134211258 | C>A,T | 0.135 | intergenic_variant | LARP1BP3 - CCDC160 | 2e-06 | Tier 4: intronic/intergenic |
| rs10958998 | 9 | 10275798 | A>C,G | 0.029 | intron_variant | PTPRD | 4e-06 | Tier 4: intronic/intergenic |
| rs11822667 | 11 | 127590676 | G>A,T | 0.055 | intergenic_variant | RN7SKP279 - DNAJB6P1 | 4e-06 | Tier 4: intronic/intergenic |
| rs12542759 | 8 | 132022590 | T>G | 0.288 | intergenic_variant | EFR3A - OC90 | 4e-06 | Tier 4: intronic/intergenic |
| rs758569 | 10 | 117433642 | C>A,G,T | 0.362 | intron_variant | PDZD8 - EMX2OS | 4e-06 | Tier 4: intronic/intergenic |
| rs197480 | 6 | 142749368 | C>T | 0.039 | intron_variant | ADGRG6 - HIVEP2 | 4e-06 | Tier 4: intronic/intergenic |
| rs9311745 | 3 | 60016099 | T>C | 0.047 | intron_variant | FHIT | 5e-06 | Tier 4: intronic/intergenic |
| rs9504361 | 6 | 577820 | A>G | 0.45 | intron_variant | EXOC2 | 6e-06 | Tier 4: intronic/intergenic |
| rs6806253 | 3 | 128563854 | A>G | 0.17 | non_coding_transcript_exon_variant | GATA2-AS1 - LINC01565 | 6e-06 | Tier 4: intronic/intergenic |
| rs2022068 | 22 | 36803762 | A>G | 0.393 | intron_variant | PVALB | 7e-06 | Tier 4: intronic/intergenic |
| rs10486722 | 7 | 41772310 | C>T | 0.335 | intron_variant | INHBA-AS1 | 7e-06 | Tier 4: intronic/intergenic |
| rs7121800 | 11 | 30543030 | T>C | 0.346 | intron_variant | MPPED2 | 7e-06 | Tier 4: intronic/intergenic |
| rs17013524 | 3 | 2381443 | T>A,C,G | 0.058 | intron_variant | CNTN4 | 9e-06 | Tier 4: intronic/intergenic |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| CHM | Orphanet:180 | Choroideremia |
| BCOR | Orphanet:2712 | Oculofaciocardiodental syndrome |
| BCOR | Orphanet:457246 | Clear cell sarcoma of kidney |
| BCOR | Orphanet:520 | Acute promyelocytic leukemia |
| BCOR | Orphanet:568 | Microphthalmia, Lenz type |
| HIVEP2 | Orphanet:178469 | Autosomal dominant non-syndromic intellectual disability |
| INHBA | Orphanet:213504 | Adenocarcinoma of ovary |
Cohort genes → proteins
15 cohort genes, 12 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| gwas_only | 15 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| MPPED2 | HGNC:1180 | ENSG00000066382 | Q15777 | Metallophosphoesterase MPPED2 | gwas |
| RBFOX1 | HGNC:18222 | ENSG00000078328 | Q9NWB1 | RNA binding protein fox-1 homolog 1 | gwas |
| EMX2OS | HGNC:18511 | ENSG00000229847 | EMX2 opposite strand/antisense RNA | gwas | |
| CHM | HGNC:1940 | ENSG00000188419 | P24386 | Rab proteins geranylgeranyltransferase component A 1 | gwas |
| BCOR | HGNC:20893 | ENSG00000183337 | Q6W2J9 | BCL-6 corepressor | gwas |
| CNTN4 | HGNC:2174 | ENSG00000144619 | Q8IWV2 | Contactin-4 | gwas |
| FAM110B | HGNC:28587 | ENSG00000169122 | Q8TC76 | Protein FAM110B | gwas |
| CCDC160 | HGNC:37286 | ENSG00000203952 | A6NGH7 | Coiled-coil domain-containing protein 160 | gwas |
| INHBA-AS1 | HGNC:40303 | ENSG00000224116 | INHBA antisense RNA 1 | gwas | |
| HIVEP2 | HGNC:4921 | ENSG00000010818 | P31629 | Transcription factor HIVEP2 | gwas |
| LINC01446 | HGNC:50773 | ENSG00000205628 | long intergenic non-protein coding RNA 1446 | gwas | |
| INHBA | HGNC:6066 | ENSG00000122641 | P08476 | Inhibin beta A chain | gwas |
| KPNA4 | HGNC:6397 | ENSG00000186432 | O00629 | Importin subunit alpha-3 | gwas |
| OC90 | HGNC:8100 | ENSG00000253117 | Q02509 | Otoconin-90 | gwas |
| PTPRD | HGNC:9668 | ENSG00000153707 | P23468 | Receptor-type tyrosine-protein phosphatase delta | gwas |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| MPPED2 | Metallophosphoesterase MPPED2 | Displays low metallophosphoesterase activity (in vitro). |
| RBFOX1 | RNA binding protein fox-1 homolog 1 | RNA-binding protein that regulates alternative splicing events by binding to 5’-UGCAUGU-3’ elements. |
| CHM | Rab proteins geranylgeranyltransferase component A 1 | Substrate-binding subunit of the Rab geranylgeranyltransferase (GGTase) complex. |
| BCOR | BCL-6 corepressor | Transcriptional corepressor. |
| CNTN4 | Contactin-4 | Contactins mediate cell surface interactions during nervous system development. |
| FAM110B | Protein FAM110B | May be involved in tumor progression. |
| HIVEP2 | Transcription factor HIVEP2 | This protein specifically binds to the DNA sequence 5’-GGGACTTTCC-3’ which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV1. |
| INHBA | Inhibin beta A chain | Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion,… |
| KPNA4 | Importin subunit alpha-3 | Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. |
| OC90 | Otoconin-90 | Major protein of the otoconia, a calcium carbonate structure in the saccule and utricle of the ear. |
| PTPRD | Receptor-type tyrosine-protein phosphatase delta | Can bidirectionally induce pre- and post-synaptic differentiation of neurons by mediating interaction with IL1RAP and IL1RAPL1 trans-synaptically. |
Protein-family classification
Druggable: 3 · Difficult: 2 · Unknown: 10 · Druggable fraction: 0.2
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 |
|---|---|---|---|
| Phosphatase | 1 | 5.6× | 0.815 |
| Antibody/Immunoglobulin | 1 | 1.9× | 0.815 |
| Other/Unknown | 10 | 1.2× | 0.815 |
| Scaffold/PPI | 1 | 1.1× | 0.856 |
| Enzyme (other) | 1 | 0.8× | 0.856 |
| Transcription factor | 1 | 0.6× | 0.856 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| MPPED2 | Other/Unknown | no | Calcineurin-like_PHP, Calcineurin-like_Pesterase, Metallo-depent_PP-like | |
| RBFOX1 | Other/Unknown | no | RRM_dom, Nucleotide-bd_a/b_plait_sf, RBFOX1-3 | |
| EMX2OS | Other/Unknown | no | ||
| CHM | Enzyme (other) | yes | 2.5.1.60 | Rab_escort, GDP_dissociation_inhibitor, FAD/NAD-bd_sf |
| BCOR | Scaffold/PPI | no | Ankyrin_rpt, BCOR, PUFD | |
| CNTN4 | Antibody/Immunoglobulin | yes | Ig_sub2, Ig_sub, FN3_dom | |
| FAM110B | Other/Unknown | no | FAM110_N, FAM110, FAM110_C | |
| CCDC160 | Other/Unknown | no | ||
| INHBA-AS1 | Other/Unknown | no | ||
| HIVEP2 | Transcription factor | no | Znf_C2H2_type, Znf_C2H2_sf, | |
| LINC01446 | Other/Unknown | no | ||
| INHBA | Other/Unknown | no | Inhibin_betaA, TGF-b_propeptide, TGF-b_C | |
| KPNA4 | Other/Unknown | no | Armadillo, Importin-a_IBB, ARM-like | |
| OC90 | Other/Unknown | no | PLA2, PLA2-like_dom, PLA2_Asp_AS | |
| PTPRD | Phosphatase | yes | 3.1.3.48 | PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat |
Expression context
Cohort genes with no expression data: 0.
14 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) | 1 |
| broad (>20) | 14 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| cortical plate | 6 |
| ganglionic eminence | 4 |
| middle temporal gyrus | 3 |
| buccal mucosa cell | 3 |
| Brodmann (1909) area 23 | 2 |
| lateral nuclear group of thalamus | 2 |
| cartilage tissue | 2 |
| vena cava | 2 |
| male germ line stem cell (sensu Vertebrata) in testis | 2 |
| ventricular zone | 1 |
| caput epididymis | 1 |
| corpus epididymis | 1 |
| kidney epithelium | 1 |
| endothelial cell | 1 |
| sperm | 1 |
| olfactory segment of nasal mucosa | 1 |
| oviduct epithelium | 1 |
| amygdala | 1 |
| nucleus accumbens | 1 |
| tendon of biceps brachii | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| MPPED2 | 255 | broad | marker | ventricular zone, ganglionic eminence, cortical plate |
| RBFOX1 | 220 | broad | marker | middle temporal gyrus, Brodmann (1909) area 23, cortical plate |
| EMX2OS | 205 | broad | marker | corpus epididymis, kidney epithelium, caput epididymis |
| CHM | 264 | ubiquitous | marker | endothelial cell, Brodmann (1909) area 23, middle temporal gyrus |
| BCOR | 265 | ubiquitous | marker | buccal mucosa cell, ganglionic eminence, cortical plate |
| CNTN4 | 214 | broad | marker | sperm, buccal mucosa cell, lateral nuclear group of thalamus |
| FAM110B | 238 | ubiquitous | marker | cortical plate, cartilage tissue, middle temporal gyrus |
| CCDC160 | 142 | broad | marker | oviduct epithelium, buccal mucosa cell, olfactory segment of nasal mucosa |
| INHBA-AS1 | 142 | tissue_specific | marker | nucleus accumbens, amygdala, ganglionic eminence |
| HIVEP2 | 296 | ubiquitous | marker | tendon of biceps brachii, vena cava, lateral nuclear group of thalamus |
| LINC01446 | 120 | tissue_specific | marker | male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, placenta |
| INHBA | 235 | ubiquitous | marker | cartilage tissue, saphenous vein, vena cava |
| KPNA4 | 289 | ubiquitous | marker | biceps brachii, skeletal muscle tissue of biceps brachii, skeletal muscle tissue of rectus abdominis |
| OC90 | 17 | tissue_specific | yes | male germ line stem cell (sensu Vertebrata) in testis, cortical plate, ganglionic eminence |
| PTPRD | 160 | broad | marker | cortical plate, right hemisphere of cerebellum, cerebellar hemisphere |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| KPNA4 | 4,085 |
| PTPRD | 3,052 |
| RBFOX1 | 2,990 |
| INHBA | 2,212 |
| BCOR | 2,188 |
| CNTN4 | 1,983 |
| HIVEP2 | 1,489 |
| CHM | 1,445 |
| CCDC160 | 989 |
| MPPED2 | 766 |
Structural data
PDB: 5 · AlphaFold-only: 7 · No structure: 3
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| KPNA4 | O00629 | 17 |
| INHBA | P08476 | 16 |
| PTPRD | P23468 | 8 |
| BCOR | Q6W2J9 | 5 |
| RBFOX1 | Q9NWB1 | 4 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| MPPED2 | Q15777 | 95.43 |
| CNTN4 | Q8IWV2 | 86.72 |
| CHM | P24386 | 81.05 |
| CCDC160 | A6NGH7 | 72.79 |
| OC90 | Q02509 | 66.43 |
| FAM110B | Q8TC76 | 59.48 |
| HIVEP2 | P31629 | 36.43 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 29. Enrichment computed across 15 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 |
|---|---|---|---|---|
| Antagonism of Activin by Follistatin | 1 | 475.8× | 0.025 | INHBA |
| TGFBR3 regulates activin signaling | 1 | 475.8× | 0.025 | INHBA |
| MECP2 regulates transcription factors | 1 | 380.7× | 0.025 | RBFOX1 |
| Peptide hormone biosynthesis | 1 | 237.9× | 0.030 | INHBA |
| Glycoprotein hormones | 1 | 158.6× | 0.033 | INHBA |
| Signaling by Activin | 1 | 126.9× | 0.033 | INHBA |
| TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain | 1 | 126.9× | 0.033 | CHM |
| Receptor-type tyrosine-protein phosphatases | 1 | 95.2× | 0.035 | PTPRD |
| Synaptic adhesion-like molecules | 1 | 90.6× | 0.035 | PTPRD |
| Signaling by TGFBR3 | 1 | 61.4× | 0.044 | INHBA |
| Signaling by BMP | 1 | 59.5× | 0.044 | INHBA |
| NS1 Mediated Effects on Host Pathways | 1 | 47.6× | 0.049 | KPNA4 |
| Peptide hormone metabolism | 1 | 45.3× | 0.049 | INHBA |
| Maturation of DENV proteins | 1 | 35.2× | 0.057 | KPNA4 |
| Antimicrobial mechanism of IFN-stimulated genes | 1 | 32.8× | 0.057 | KPNA4 |
| Influenza Infection | 1 | 29.3× | 0.057 | KPNA4 |
| RAB geranylgeranylation | 1 | 28.8× | 0.057 | CHM |
| Post-translational modification: synthesis of GPI-anchored proteins | 1 | 28.0× | 0.057 | CNTN4 |
| ISG15 antiviral mechanism | 1 | 25.0× | 0.060 | KPNA4 |
| RAB GEFs exchange GTP for GDP on RABs | 1 | 20.7× | 0.067 | CHM |
| Interferon Signaling | 1 | 20.0× | 0.067 | KPNA4 |
| Signaling by TGFB family members | 1 | 19.2× | 0.067 | INHBA |
| Cytokine Signaling in Immune system | 1 | 6.8× | 0.175 | KPNA4 |
| Viral Infection Pathways | 1 | 5.1× | 0.217 | KPNA4 |
| Infectious disease | 1 | 4.1× | 0.254 | KPNA4 |
| Disease | 1 | 2.2× | 0.411 | KPNA4 |
| Immune System | 1 | 2.2× | 0.411 | KPNA4 |
| Metabolism of proteins | 1 | 2.1× | 0.411 | INHBA |
| Signal Transduction | 1 | 1.7× | 0.463 | INHBA |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| nervous system development | 4 | 20.4× | 0.003 | RBFOX1, CNTN4, INHBA, PTPRD |
| odontogenesis | 2 | 117.0× | 0.007 | BCOR, INHBA |
| regulation of follicle-stimulating hormone secretion | 1 | 1872.4× | 0.009 | INHBA |
| cardiac fibroblast cell development | 1 | 1872.4× | 0.009 | INHBA |
| specification of axis polarity | 1 | 1872.4× | 0.009 | BCOR |
| androst-4-ene-3,17-dione biosynthetic process | 1 | 1872.4× | 0.009 | INHBA |
| roof of mouth development | 2 | 55.1× | 0.009 | BCOR, INHBA |
| progesterone secretion | 1 | 936.2× | 0.012 | INHBA |
| positive regulation of ovulation | 1 | 936.2× | 0.012 | INHBA |
| negative regulation of tooth mineralization | 1 | 936.2× | 0.012 | BCOR |
| otolith mineralization | 1 | 624.1× | 0.014 | OC90 |
| negative regulation of follicle-stimulating hormone secretion | 1 | 624.1× | 0.014 | INHBA |
| trans-synaptic signaling by trans-synaptic complex | 1 | 624.1× | 0.014 | PTPRD |
| striatal medium spiny neuron differentiation | 1 | 468.1× | 0.016 | INHBA |
| cellular response to oxygen-glucose deprivation | 1 | 468.1× | 0.016 | INHBA |
| negative regulation of B cell differentiation | 1 | 374.5× | 0.016 | INHBA |
| GABAergic neuron differentiation | 1 | 374.5× | 0.016 | INHBA |
| protein geranylgeranylation | 1 | 312.1× | 0.016 | CHM |
| negative regulation of phosphorylation | 1 | 312.1× | 0.016 | INHBA |
| hemoglobin biosynthetic process | 1 | 312.1× | 0.016 | INHBA |
| positive regulation of follicle-stimulating hormone secretion | 1 | 312.1× | 0.016 | INHBA |
| testosterone biosynthetic process | 1 | 312.1× | 0.016 | INHBA |
| cell surface receptor protein tyrosine phosphatase signaling pathway | 1 | 234.1× | 0.020 | PTPRD |
| negative regulation of macrophage differentiation | 1 | 234.1× | 0.020 | INHBA |
| presynaptic membrane assembly | 1 | 187.2× | 0.022 | PTPRD |
| response to aldosterone | 1 | 187.2× | 0.022 | INHBA |
| mesodermal cell differentiation | 1 | 170.2× | 0.022 | INHBA |
| RNA transport | 1 | 170.2× | 0.022 | RBFOX1 |
| Sertoli cell differentiation | 1 | 170.2× | 0.022 | INHBA |
| positive regulation of extrinsic apoptotic signaling pathway in absence of ligand | 1 | 170.2× | 0.022 | INHBA |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 15
Druggability breadth: 6 of 15 evidence-associated genes (40%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| MPPED2 | 0 | 0 |
| RBFOX1 | 0 | 0 |
| EMX2OS | 0 | 0 |
| CHM | 0 | 0 |
| BCOR | 0 | 0 |
| CNTN4 | 0 | 0 |
| FAM110B | 0 | 0 |
| CCDC160 | 0 | 0 |
| INHBA-AS1 | 0 | 0 |
| HIVEP2 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 2.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| INHBA | 3 | Binding:3 |
| BCOR | 2 | Binding:2 |
| CHM | 1 | Binding:1 |
| HIVEP2 | 1 | Binding:1 |
| KPNA4 | 1 | Binding:1 |
| PTPRD | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| CHM | 2.5.1.60 | protein geranylgeranyltransferase type II |
| PTPRD | 3.1.3.48 | protein-tyrosine-phosphatase |
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
0 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.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | PTPRD |
| D | Druggable family + AlphaFold only, no drug | 2 | CHM, CNTN4 |
| E | Difficult family or no structure, no drug | 12 | MPPED2, RBFOX1, EMX2OS, BCOR, FAM110B, CCDC160, INHBA-AS1, HIVEP2, LINC01446, INHBA (+2 more) |
Undrugged target profiles
15 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| MPPED2 | 0 | — |
| RBFOX1 | 0 | — |
| EMX2OS | 0 | — |
| CHM | 1 | — |
| BCOR | 2 | — |
| CNTN4 | 0 | — |
| FAM110B | 0 | — |
| CCDC160 | 0 | — |
| INHBA-AS1 | 0 | — |
| HIVEP2 | 1 | — |
| LINC01446 | 0 | — |
| INHBA | 3 | — |
| KPNA4 | 1 | — |
| OC90 | 0 | — |
| PTPRD | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.