Laron syndrome

Summary

Laron syndrome (MONDO:0009877) is a disease caused by GHR (GenCC Definitive), with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include mecasermin rinfabate.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: GHR (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 138
• Phenotypes (HPO): 29
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.3	Europe	Validated
Point prevalence	1-9 / 100 000	4.86	China	Validated

Signs & symptoms

Clinical features (HPO)

29 HPO clinical features (Orphanet curated; top 29 by frequency):

HPO ID	Term	Frequency
HP:0000347	Micrognathia	Very frequent (80-99%)
HP:0000348	High forehead	Very frequent (80-99%)
HP:0000684	Delayed eruption of teeth	Very frequent (80-99%)
HP:0000691	Microdontia	Very frequent (80-99%)
HP:0000818	Abnormality of the endocrine system	Very frequent (80-99%)
HP:0001956	Truncal obesity	Very frequent (80-99%)
HP:0001999	Abnormal facial shape	Very frequent (80-99%)
HP:0002750	Delayed skeletal maturation	Very frequent (80-99%)
HP:0003510	Severe short stature	Very frequent (80-99%)
HP:0005281	Hypoplastic nasal bridge	Very frequent (80-99%)
HP:0009804	Tooth agenesis	Very frequent (80-99%)
HP:0009924	Aplasia/Hypoplasia involving the nose	Very frequent (80-99%)
HP:0000823	Delayed puberty	Frequent (30-79%)
HP:0001156	Brachydactyly	Frequent (30-79%)
HP:0001270	Motor delay	Frequent (30-79%)
HP:0001831	Short toe	Frequent (30-79%)
HP:0001943	Hypoglycemia	Frequent (30-79%)
HP:0008736	Hypoplasia of penis	Frequent (30-79%)
HP:0009811	Abnormality of the elbow	Frequent (30-79%)
HP:0009891	Underdeveloped supraorbital ridges	Frequent (30-79%)
HP:0000457	Depressed nasal ridge	Occasional (5-29%)
HP:0000592	Blue sclerae	Occasional (5-29%)
HP:0000929	Abnormal skull morphology	Occasional (5-29%)
HP:0000966	Hypohidrosis	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001620	Abnormally high-pitched voice	Occasional (5-29%)
HP:0002758	Osteoarthritis	Occasional (5-29%)
HP:0003124	Hypercholesterolemia	Occasional (5-29%)
HP:0007495	Prematurely aged appearance	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Laron syndrome
Mondo ID	MONDO:0009877
MeSH	D046150
OMIM	262500
Orphanet	633
DOID	DOID:9521
NCIT	C130994
SNOMED CT	38196001
UMLS	C0271568
MedGen	78776
GARD	0006859
NORD	1209
Is cancer (heuristic)	no

Also known as: complete growth hormone insensitivity · GH receptor deficiency · Growth Hormone Insensitivity · Growth hormone receptor deficiency · Laron dwarfism · Laron syndrome · Laron type pituitary dwarfism I · Laron-type dwarfism · pituitary dwarfism II · primary GH insensitivity · primary GH resistance · primary growth hormone insensitivity · primary growth hormone resistance · short stature due to growth hormone resistance

Data availability: 138 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › Laron syndrome

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

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

138 retrieved; paginated sample, class counts are floors:

65 uncertain significance, 22 conflicting classifications of pathogenicity, 19 pathogenic, 18 benign, 6 likely benign, 4 pathogenic/likely pathogenic, 3 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1206352	NM_000163.5(GHR):c.192_193del (p.Ser65fs)	GHR	Pathogenic	criteria provided, multiple submitters, no conflicts
1804177	NM_000163.5(GHR):c.267-1155_333del	GHR	Pathogenic	criteria provided, single submitter
2734726	NM_000163.5(GHR):c.335G>T (p.Cys112Phe)	GHR	Pathogenic	criteria provided, multiple submitters, no conflicts
397577	NM_000163.5(GHR):c.281G>A (p.Trp94Ter)	GHR	Pathogenic	no assertion criteria provided
492774	NM_000163.5(GHR):c.945G>A (p.Lys315=)	GHR	Pathogenic	criteria provided, single submitter
807419	NM_000163.5(GHR):c.344A>C (p.Asn115Thr)	GHR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8631	GHR, EX4,6DEL	GHR	Pathogenic	no assertion criteria provided
8632	NM_000163.5(GHR):c.341T>C (p.Phe114Ser)	GHR	Pathogenic	no assertion criteria provided
8633	NM_000163.5(GHR):c.181C>T (p.Arg61Ter)	GHR	Pathogenic	criteria provided, multiple submitters, no conflicts
8634	NM_000163.5(GHR):c.168C>A (p.Cys56Ter)	GHR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8635	NM_000163.5(GHR):c.594A>G (p.Glu198=)	GHR	Pathogenic	criteria provided, multiple submitters, no conflicts
8639	NM_000163.5(GHR):c.703C>T (p.Arg235Ter)	GHR	Pathogenic	criteria provided, multiple submitters, no conflicts
8640	NM_000163.5(GHR):c.266+1G>A	GHR	Pathogenic	criteria provided, single submitter
8642	NM_000163.5(GHR):c.619-1G>T	GHR	Pathogenic	criteria provided, single submitter
8643	NM_000163.5(GHR):c.743_744del (p.Tyr248fs)	GHR	Pathogenic	no assertion criteria provided
8645	NM_000163.5(GHR):c.515A>C (p.Gln172Pro)	GHR	Pathogenic	no assertion criteria provided
8648	NM_000163.5(GHR):c.518T>G (p.Val173Gly)	GHR	Pathogenic	criteria provided, single submitter
8655	NM_000163.5(GHR):c.618+792A>G	GHR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8656	NP_000154.1:p.Ala442Serfs*27	GHR	Pathogenic	no assertion criteria provided
8657	NM_000163.5(GHR):c.102G>A (p.Trp34Ter)	GHR	Pathogenic	criteria provided, single submitter
8659	NM_000163.5(GHR):c.303C>A (p.Cys101Ter)	GHR	Pathogenic	criteria provided, single submitter
8662	NM_000163.5(GHR):c.335G>C (p.Cys112Ser)	GHR	Pathogenic	no assertion criteria provided
869191	NM_000163.5(GHR):c.267-2A>G	GHR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1332694	NM_000163.5(GHR):c.70+5G>A	GHR	Likely pathogenic	criteria provided, single submitter
3024216	NC_000005.10:g.(42700003_42711206)(42719424?)del	GHR	Likely pathogenic	criteria provided, single submitter
8660	NM_000163.5(GHR):c.1734del (p.Arg578fs)	GHR	Likely pathogenic	criteria provided, single submitter
1298991	NM_000163.5(GHR):c.503A>C (p.His168Pro)	GHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1427764	NM_000163.5(GHR):c.484G>T (p.Val162Phe)	GHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1442875	NM_000163.5(GHR):c.784+6A>G	GHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1705333	NM_000163.5(GHR):c.723C>T (p.Gly241=)	GHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
GHR	Definitive	Autosomal recessive	Laron syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GHR	Orphanet:314802	Short stature due to partial GHR deficiency
GHR	Orphanet:633	Laron syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GHR	HGNC:4263	ENSG00000112964	P10912	Growth hormone receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GHR	Growth hormone receptor	Receptor for pituitary gland growth hormone (GH1) involved in regulating postnatal body growth.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GHR	Antibody/Immunoglobulin	yes		Long_hematopoietin_rcpt_CS, FN3_dom, Ig-like_fold

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
biceps brachii	1
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GHR	248	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii, biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GHR	1,511

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GHR	P10912	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Prolactin receptor signaling	1	761.3×	0.002	GHR
Growth hormone receptor signaling	1	475.8×	0.002	GHR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of response to nutrient levels	1	16852.0×	0.001	GHR
response to cycloheximide	1	5617.3×	0.002	GHR
response to gravity	1	2808.7×	0.002	GHR
taurine metabolic process	1	2808.7×	0.002	GHR
cartilage development involved in endochondral bone morphogenesis	1	2407.4×	0.002	GHR
growth hormone receptor signaling pathway	1	1203.7×	0.003	GHR
hormone metabolic process	1	887.0×	0.004	GHR
regulation of multicellular organism growth	1	648.1×	0.004	GHR
response to interleukin-1	1	510.7×	0.004	GHR
response to food	1	495.6×	0.004	GHR
positive regulation of multicellular organism growth	1	495.6×	0.004	GHR
insulin-like growth factor receptor signaling pathway	1	495.6×	0.004	GHR
positive regulation of receptor signaling pathway via JAK-STAT	1	432.1×	0.004	GHR
hormone-mediated signaling pathway	1	401.2×	0.004	GHR
cellular response to hormone stimulus	1	383.0×	0.004	GHR
receptor internalization	1	324.1×	0.005	GHR
response to glucocorticoid	1	324.1×	0.005	GHR
cell surface receptor signaling pathway via JAK-STAT	1	290.6×	0.005	GHR
positive regulation of cell differentiation	1	267.5×	0.005	GHR
response to estradiol	1	198.3×	0.006	GHR
cellular response to insulin stimulus	1	170.2×	0.007	GHR
cytokine-mediated signaling pathway	1	130.6×	0.009	GHR
endocytosis	1	95.2×	0.011	GHR
positive regulation of MAPK cascade	1	80.6×	0.013	GHR
positive regulation of cell population proliferation	1	33.6×	0.030	GHR

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Mecasermin	Approved (phase 4)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Mecasermin Rinfabate.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GHR	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
GHR	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	GHR
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GHR	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00368173	PHASE2/PHASE3	COMPLETED	IGF-I/IGFBP-3 Therapy in Children and Adolescents With Growth Hormone Insenitivity Syndrome (GHIS) Such as Laron Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MECASERMIN RINFABATE	4	1