isolated growth hormone deficiency type IA
diseaseOn this page
Also known as congenital IGHDcongenital IGHD type IAcongenital isolated GH deficiencycongenital isolated GH deficiency type IAcongenital isolated growth hormone deficiencycongenital isolated growth hormone deficiency type IAGrowth hormone deficiency, isolated autosomal recessivegrowth hormone deficiency, isolated, type IAIGHD1AILLIG type growth hormone deficiencyIllig-type growth hormone deficiencyisolated growth hormone deficiency type 1Aisolated growth hormone deficiency, type IAnon-acquired isolated growth hormone deficiencypituitary dwarfism 1primordial dwarfismsexual ateleiotic dwarfism
Summary
isolated growth hormone deficiency type IA (MONDO:0009876) is a disease caused by GH1 (GenCC Definitive), with 8 cohort genes.
At a glance
- Causal gene: GH1 (GenCC Definitive)
- Cohort genes: 8
- ClinVar variants: 25
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | isolated growth hormone deficiency type IA |
| Mondo ID | MONDO:0009876 |
| MeSH | C537404 |
| OMIM | 262400 |
| Orphanet | 231662 |
| DOID | DOID:0060873 |
| SNOMED CT | 237837007 |
| UMLS | C0342573 |
| MedGen | 90986 |
| GARD | 0007399 |
| Is cancer (heuristic) | no |
Also known as: congenital IGHD · congenital IGHD type IA · congenital isolated GH deficiency · congenital isolated GH deficiency type IA · congenital isolated growth hormone deficiency · congenital isolated growth hormone deficiency type IA · Growth hormone deficiency, isolated autosomal recessive · growth hormone deficiency, isolated, type IA · IGHD1A · ILLIG type growth hormone deficiency · Illig-type growth hormone deficiency · isolated growth hormone deficiency type 1A · isolated growth hormone deficiency type IA · isolated growth hormone deficiency, type IA · non-acquired isolated growth hormone deficiency · pituitary dwarfism 1 · primordial dwarfism · sexual ateleiotic dwarfism
Data availability: 25 ClinVar variants · 5 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › combined pituitary hormone deficiencies, genetic form › isolated congenital growth hormone deficiency › isolated growth hormone deficiency type IA
Related subtypes (6): isolated growth hormone deficiency type II, short stature due to growth hormone qualitative anomaly, isolated growth hormone deficiency type III, isolated growth hormone deficiency type IB, isolated growth hormone deficiency, type 4, isolated growth hormone deficiency, type 5
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
25 retrieved; paginated sample, class counts are floors:
10 pathogenic, 9 uncertain significance, 2 pathogenic/likely pathogenic, 2 benign/likely benign, 1 likely pathogenic, 1 conflicting classifications of pathogenicity
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 127241 | NM_000059.4(BRCA2):c.9152del (p.Pro3051fs) | BRCA2 | Pathogenic | reviewed by expert panel |
| 127249 | NM_014171.6(CRIPT):c.133_134insGG (p.Ala45fs) | CRIPT | Pathogenic | no assertion criteria provided |
| 127250 | NM_014171.6(CRIPT):c.141del (p.Phe47fs) | CRIPT | Pathogenic | no assertion criteria provided |
| 143932 | NM_001080449.3(DNA2):c.3114+6del | DNA2 | Pathogenic/Likely pathogenic | no assertion criteria provided |
| 15970 | NM_000515.5(GH1):c.291+1G>A | GH-LCR | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 15962 | NM_000515.5(GH1):c.245_246del (p.Glu82fs) | GH1 | Pathogenic | no assertion criteria provided |
| 15963 | NM_000515.5(GH1):c.59G>A (p.Trp20Ter) | GH1 | Pathogenic | criteria provided, single submitter |
| 15964 | GH1, 6.7-KB DEL | GH1 | Pathogenic | no assertion criteria provided |
| 15965 | NM_000515.5(GH1):c.52del (p.Leu18fs) | GH1 | Pathogenic | no assertion criteria provided |
| 2431647 | NC_000017.11:g.(63914995_63921260)del | GH1 | Pathogenic | criteria provided, single submitter |
| 37062 | NM_015426.5(POC1A):c.241C>T (p.Arg81Ter) | POC1A | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 127246 | NM_003401.5(XRCC4):c.127T>C (p.Trp43Arg) | XRCC4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1013138 | NM_000515.5(GH1):c.178G>A (p.Ala60Thr) | GH1 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1723212 | NM_000515.5(GH1):c.11-8C>T | CSHL1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1033063 | NM_000515.5(GH1):c.188_195delinsTGAAGGAG (p.Pro63Leu) | GH-LCR | Uncertain significance | criteria provided, single submitter |
| 15966 | NM_000515.5(GH1):c.456+1G>C | GH-LCR | Uncertain significance | criteria provided, single submitter |
| 3582621 | NM_000515.5(GH1):c.595G>C (p.Val199Leu) | GH-LCR | Uncertain significance | criteria provided, single submitter |
| 431860 | NM_000515.5(GH1):c.217A>G (p.Asn73Asp) | GH-LCR | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 892518 | NM_000515.5(GH1):c.350A>G (p.Gln117Arg) | GH-LCR | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 982612 | NM_000515.5(GH1):c.502A>T (p.Thr168Ser) | GH-LCR | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1030836 | NM_000515.5(GH1):c.588G>A (p.Met196Ile) | GH1 | Uncertain significance | criteria provided, single submitter |
| 3234046 | NM_000515.5(GH1):c.47_55del (p.Leu16_Leu18del) | GH1 | Uncertain significance | criteria provided, single submitter |
| 3582622 | NM_000515.5(GH1):c.346G>A (p.Val116Met) | GH1 | Uncertain significance | criteria provided, single submitter |
| 1635025 | NM_000515.5(GH1):c.456+19G>T | GH-LCR | Benign/Likely benign | criteria provided, multiple submitters, no conflicts |
| 284727 | NM_000515.5(GH1):c.116C>T (p.Ala39Val) | GH-LCR | Benign/Likely benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 16 · Orphanet: 24 · 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 |
|---|---|---|---|---|
| GH1 | Definitive | Autosomal recessive | isolated growth hormone deficiency type IA | 11 |
| RNPC3 | Definitive | Autosomal recessive | isolated growth hormone deficiency, type 5 | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| GH1 | Orphanet:231662 | Isolated growth hormone deficiency type IA |
| GH1 | Orphanet:231671 | Isolated growth hormone deficiency type IB |
| GH1 | Orphanet:231679 | Isolated growth hormone deficiency type II |
| GH1 | Orphanet:629 | Short stature due to growth hormone qualitative anomaly |
| RNPC3 | Orphanet:231662 | Isolated growth hormone deficiency type IA |
| BRCA2 | Orphanet:1331 | Familial prostate cancer |
| BRCA2 | Orphanet:1333 | Familial pancreatic carcinoma |
| BRCA2 | Orphanet:145 | Hereditary breast and/or ovarian cancer syndrome |
| BRCA2 | Orphanet:178 | Chordoma |
| BRCA2 | Orphanet:227535 | Hereditary breast cancer |
| BRCA2 | Orphanet:319462 | Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations |
| BRCA2 | Orphanet:440437 | Familial colorectal cancer Type X |
| BRCA2 | Orphanet:654 | Nephroblastoma |
| BRCA2 | Orphanet:667662 | Breast implant-associated anaplastic large cell lymphoma |
| BRCA2 | Orphanet:694963 | Inflammatory breast cancer |
| BRCA2 | Orphanet:70567 | Cholangiocarcinoma |
| BRCA2 | Orphanet:84 | Fanconi anemia |
| XRCC4 | Orphanet:436182 | Microcephalic primordial dwarfism-insulin resistance syndrome |
| XRCC4 | Orphanet:99812 | LIG4 syndrome |
| CRIPT | Orphanet:715640 | Rothmund-Thomson syndrome type 3 |
| POC1A | Orphanet:314394 | Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome |
| DNA2 | Orphanet:352470 | DNA2-related mitochondrial DNA deletion syndrome |
| DNA2 | Orphanet:715635 | Rothmund-Thomson syndrome type 4 |
| DNA2 | Orphanet:808 | Seckel syndrome |
Cohort genes → proteins
8 cohort genes, 8 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 8 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| GH1 | HGNC:4261 | ENSG00000259384 | P01241 | Somatotropin | gencc,clinvar |
| RNPC3 | HGNC:18666 | ENSG00000185946 | Q96LT9 | RNA-binding region-containing protein 3 | gencc |
| BRCA2 | HGNC:1101 | ENSG00000139618 | P51587 | Breast cancer type 2 susceptibility protein | clinvar |
| XRCC4 | HGNC:12831 | ENSG00000152422 | Q13426 | DNA repair protein XRCC4 | clinvar |
| CRIPT | HGNC:14312 | ENSG00000119878 | Q9P021 | Cysteine-rich PDZ-binding protein | clinvar |
| CSHL1 | HGNC:2442 | ENSG00000204414 | Q14406 | Chorionic somatomammotropin hormone-like 1 | clinvar |
| POC1A | HGNC:24488 | ENSG00000164087 | Q8NBT0 | POC1 centriolar protein homolog A | clinvar |
| DNA2 | HGNC:2939 | ENSG00000138346 | P51530 | DNA replication ATP-dependent helicase/nuclease DNA2 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| GH1 | Somatotropin | Plays an important role in growth control. |
| RNPC3 | RNA-binding region-containing protein 3 | Participates in pre-mRNA U12-dependent splicing, performed by the minor spliceosome which removes U12-type introns. |
| BRCA2 | Breast cancer type 2 susceptibility protein | Involved in double-strand break repair and/or homologous recombination. |
| XRCC4 | DNA repair protein XRCC4 | DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination. |
| CRIPT | Cysteine-rich PDZ-binding protein | As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. |
| CSHL1 | Chorionic somatomammotropin hormone-like 1 | May be a novel gestational hormone required to compensate for absence of other members of the GH/CS cluster during gestation. |
| POC1A | POC1 centriolar protein homolog A | Plays an important role in centriole assembly and/or stability and ciliogenesis. |
| DNA2 | DNA replication ATP-dependent helicase/nuclease DNA2 | Key enzyme involved in DNA replication and DNA repair in nucleus and mitochondrion. |
Protein-family classification
Druggable: 0 · Difficult: 2 · Unknown: 6 · Druggable fraction: 0.0
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 |
|---|---|---|---|
| Scaffold/PPI | 2 | 4.3× | 0.148 |
| Other/Unknown | 6 | 1.3× | 0.234 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| GH1 | Other/Unknown | no | Somatotropin/Prolactin, 4_helix_cytokine-like_core, Somatotropin_CS | |
| RNPC3 | Other/Unknown | no | RRM_dom, Nucleotide-bd_a/b_plait_sf, RBM40_RRM1 | |
| BRCA2 | Other/Unknown | no | BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1 | |
| XRCC4 | Other/Unknown | no | XRCC4_N_sf, DNA_repair_prot_XRCC4, XRCC4-like_C | |
| CRIPT | Scaffold/PPI | no | PDZ-binding_CRIPT | |
| CSHL1 | Other/Unknown | no | Somatotropin/Prolactin, 4_helix_cytokine-like_core, Somatotropin_CS | |
| POC1A | Scaffold/PPI | no | WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS | |
| DNA2 | Other/Unknown | no | PDDEXK-like_dom_sf, DNA_replication_fac_Dna2_N, Dna2/JHS1_DEXXQ-box |
Expression context
Cohort genes with no expression data: 0.
6 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) | 8 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | 3 |
| adenohypophysis | 2 |
| pituitary gland | 2 |
| caput epididymis | 2 |
| corpus epididymis | 2 |
| secondary oocyte | 2 |
| ventricular zone | 2 |
| primordial germ cell in gonad | 2 |
| right uterine tube | 1 |
| monocyte | 1 |
| mononuclear cell | 1 |
| endothelial cell | 1 |
| placenta | 1 |
| pancreatic ductal cell | 1 |
| Brodmann (1909) area 10 | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| GH1 | 119 | tissue_specific | yes | pituitary gland, adenohypophysis, male germ line stem cell (sensu Vertebrata) in testis |
| RNPC3 | 256 | ubiquitous | marker | caput epididymis, corpus epididymis, right uterine tube |
| BRCA2 | 184 | ubiquitous | marker | male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone |
| XRCC4 | 234 | ubiquitous | marker | male germ line stem cell (sensu Vertebrata) in testis, monocyte, mononuclear cell |
| CRIPT | 284 | ubiquitous | marker | endothelial cell, corpus epididymis, caput epididymis |
| CSHL1 | 29 | tissue_specific | yes | placenta, adenohypophysis, pituitary gland |
| POC1A | 164 | ubiquitous | marker | pancreatic ductal cell, ventricular zone, primordial germ cell in gonad |
| DNA2 | 192 | ubiquitous | marker | secondary oocyte, primordial germ cell in gonad, Brodmann (1909) area 10 |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| BRCA2 | 4,839 |
| DNA2 | 2,792 |
| POC1A | 2,588 |
| RNPC3 | 1,863 |
| XRCC4 | 1,494 |
| GH1 | 1,007 |
| CRIPT | 901 |
| CSHL1 | 441 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| GH1 | RNPC3 | string_interaction |
Structural data
PDB: 6 · AlphaFold-only: 2 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| XRCC4 | Q13426 | 35 |
| BRCA2 | P51587 | 14 |
| GH1 | P01241 | 10 |
| RNPC3 | Q96LT9 | 2 |
| CRIPT | Q9P021 | 1 |
| DNA2 | P51530 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| POC1A | Q8NBT0 | 85.17 |
| CSHL1 | Q14406 | 75.99 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 47. Enrichment computed across 8 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Impaired BRCA2 binding to PALB2 | 2 | 182.7× | 5e-04 | BRCA2, DNA2 |
| Defective homologous recombination repair (HRR) due to BRCA1 loss of function | 2 | 169.2× | 5e-04 | BRCA2, DNA2 |
| Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function | 2 | 169.2× | 5e-04 | BRCA2, DNA2 |
| Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function | 2 | 169.2× | 5e-04 | BRCA2, DNA2 |
| Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) | 2 | 157.5× | 5e-04 | BRCA2, DNA2 |
| Homologous DNA Pairing and Strand Exchange | 2 | 152.3× | 5e-04 | BRCA2, DNA2 |
| Impaired BRCA2 binding to RAD51 | 2 | 123.5× | 6e-04 | BRCA2, DNA2 |
| Resolution of D-loop Structures through Holliday Junction Intermediates | 2 | 120.2× | 6e-04 | BRCA2, DNA2 |
| Presynaptic phase of homologous DNA pairing and strand exchange | 2 | 108.8× | 7e-04 | BRCA2, DNA2 |
| HDR through Homologous Recombination (HRR) | 2 | 76.1× | 0.001 | BRCA2, DNA2 |
| Impaired BRCA2 translocation to the nucleus | 1 | 761.3× | 0.005 | BRCA2 |
| Impaired BRCA2 binding to SEM1 (DSS1) | 1 | 761.3× | 0.005 | BRCA2 |
| 2-LTR circle formation | 1 | 326.3× | 0.011 | XRCC4 |
| Defective homologous recombination repair (HRR) due to PALB2 loss of function | 1 | 190.3× | 0.016 | BRCA2 |
| HDR through MMEJ (alt-NHEJ) | 1 | 175.7× | 0.016 | BRCA2 |
| Removal of the Flap Intermediate | 1 | 163.1× | 0.016 | DNA2 |
| Diseases of DNA Double-Strand Break Repair | 1 | 163.1× | 0.016 | BRCA2 |
| Defective homologous recombination repair (HRR) due to BRCA2 loss of function | 1 | 163.1× | 0.016 | BRCA2 |
| Prolactin receptor signaling | 1 | 152.3× | 0.016 | GH1 |
| Removal of the Flap Intermediate from the C-strand | 1 | 126.9× | 0.018 | DNA2 |
| Resolution of D-Loop Structures | 1 | 126.9× | 0.018 | BRCA2 |
| Synthesis, secretion, and deacylation of Ghrelin | 1 | 120.2× | 0.018 | GH1 |
| Diseases of DNA repair | 1 | 114.2× | 0.018 | BRCA2 |
| Growth hormone receptor signaling | 1 | 95.2× | 0.020 | GH1 |
| Homology Directed Repair | 1 | 61.7× | 0.029 | BRCA2 |
| HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 1 | 61.7× | 0.029 | BRCA2 |
| HDR through Single Strand Annealing (SSA) | 1 | 58.6× | 0.029 | DNA2 |
| Meiosis | 1 | 57.1× | 0.029 | BRCA2 |
| Peptide hormone metabolism | 1 | 54.4× | 0.030 | GH1 |
| DNA Double-Strand Break Repair | 1 | 49.6× | 0.031 | BRCA2 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| growth hormone receptor signaling pathway | 2 | 300.9× | 0.001 | GH1, CSHL1 |
| response to X-ray | 2 | 221.7× | 0.001 | BRCA2, XRCC4 |
| animal organ development | 2 | 183.2× | 0.001 | GH1, CSHL1 |
| base-excision repair | 2 | 117.0× | 0.002 | XRCC4, DNA2 |
| positive regulation of receptor signaling pathway via JAK-STAT | 2 | 108.0× | 0.002 | GH1, CSHL1 |
| response to nutrient levels | 2 | 91.6× | 0.003 | GH1, CSHL1 |
| DNA replication, Okazaki fragment processing | 1 | 2106.5× | 0.005 | DNA2 |
| double-strand break repair | 2 | 50.8× | 0.006 | BRCA2, XRCC4 |
| mitotic recombination-dependent replication fork processing | 1 | 1053.2× | 0.008 | BRCA2 |
| growth plate cartilage chondrocyte development | 1 | 702.2× | 0.008 | POC1A |
| positive regulation of ligase activity | 1 | 702.2× | 0.008 | XRCC4 |
| bone maturation | 1 | 702.2× | 0.008 | GH1 |
| mitotic telomere maintenance via semi-conservative replication | 1 | 702.2× | 0.008 | DNA2 |
| DNA double-strand break attachment to nuclear envelope | 1 | 702.2× | 0.008 | XRCC4 |
| DNA replication, removal of RNA primer | 1 | 526.6× | 0.009 | DNA2 |
| regulation of postsynaptic density protein 95 clustering | 1 | 526.6× | 0.009 | CRIPT |
| positive regulation of centrosome duplication | 1 | 421.3× | 0.009 | POC1A |
| negative regulation of mammary gland epithelial cell proliferation | 1 | 421.3× | 0.009 | BRCA2 |
| replication fork reversal | 1 | 421.3× | 0.009 | DNA2 |
| telomere maintenance via semi-conservative replication | 1 | 351.1× | 0.010 | DNA2 |
| immunoglobulin V(D)J recombination | 1 | 351.1× | 0.010 | XRCC4 |
| mitochondrial DNA repair | 1 | 300.9× | 0.011 | DNA2 |
| positive regulation of D-glucose transmembrane transport | 1 | 263.3× | 0.011 | GH1 |
| DNA geometric change | 1 | 263.3× | 0.011 | DNA2 |
| establishment of protein localization to telomere | 1 | 263.3× | 0.011 | BRCA2 |
| RNA splicing | 2 | 22.1× | 0.011 | CRIPT, RNPC3 |
| response to UV-C | 1 | 210.7× | 0.013 | BRCA2 |
| telomere maintenance via recombination | 1 | 191.5× | 0.013 | BRCA2 |
| DNA double-strand break processing | 1 | 191.5× | 0.013 | DNA2 |
| mitochondrial DNA replication | 1 | 191.5× | 0.013 | DNA2 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 8
Druggability breadth: 2 of 8 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| GH1 | 0 | 0 |
| RNPC3 | 0 | 0 |
| BRCA2 | 0 | 0 |
| XRCC4 | 0 | 0 |
| CRIPT | 0 | 0 |
| CSHL1 | 0 | 0 |
| POC1A | 0 | 0 |
| DNA2 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| DNA2 | 23 | Binding:23 |
| XRCC4 | 1 | Binding:1 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 8; 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 | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 8 | GH1, RNPC3, BRCA2, XRCC4, CRIPT, CSHL1, POC1A, DNA2 |
Undrugged target profiles
8 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| GH1 | 0 | — |
| RNPC3 | 0 | — |
| BRCA2 | 0 | — |
| XRCC4 | 1 | — |
| CRIPT | 0 | — |
| CSHL1 | 0 | — |
| POC1A | 0 | — |
| DNA2 | 23 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.