short stature due to partial GHR deficiency

Summary

short stature due to partial GHR deficiency (MONDO:0011420) is a disease caused by GHR (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: GHR (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 32
• Phenotypes (HPO): 7

Clinical features

Signs & symptoms

Clinical features (HPO)

7 HPO clinical features (Orphanet curated; top 7 by frequency):

HPO ID	Term	Frequency
HP:0002750	Delayed skeletal maturation	Very frequent (80-99%)
HP:0001510	Growth delay	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0030353	Decreased serum insulin-like growth factor 1	Very frequent (80-99%)
HP:0000823	Delayed puberty	Occasional (5-29%)
HP:0001943	Hypoglycemia	Occasional (5-29%)
HP:0011800	Midface retrusion	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	short stature due to partial GHR deficiency
Mondo ID	MONDO:0011420
MeSH	C565805
OMIM	604271
Orphanet	314802
UMLS	C1858656
MedGen	346958
GARD	0017435
Is cancer (heuristic)	no

Also known as: GHIP · Growth hormone deficiency, isolated, partial · growth hormone insensitivity, partial · Growth hormone, insensitivity to, partial · short stature due to partial growth hormone receptor deficiency

Data availability: 32 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › adrenal gland disorder › pituitary dwarfism › short stature due to partial GHR deficiency

Related subtypes (1): psychosocial short stature

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

32 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 8 conflicting classifications of pathogenicity, 5 pathogenic, 2 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2203646	NM_000163.5(GHR):c.440-1G>A	GHR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
254180	NM_000163.5(GHR):c.559T>C (p.Trp187Arg)	GHR	Pathogenic	no assertion criteria provided
8633	NM_000163.5(GHR):c.181C>T (p.Arg61Ter)	GHR	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
8646	NM_000163.5(GHR):c.876-1G>C	GHR	Pathogenic	criteria provided, single submitter
1376396	NM_000163.5(GHR):c.1589T>C (p.Met530Thr)	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
198398	NM_000163.5(GHR):c.718T>C (p.Tyr240His)	GHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
281656	NM_000163.5(GHR):c.686G>A (p.Arg229His)	GHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
8636	NM_000163.5(GHR):c.184G>A (p.Glu62Lys)	GHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
8637	NM_000163.5(GHR):c.535C>T (p.Arg179Cys)	GHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
8638	NM_000163.5(GHR):c.726G>C (p.Glu242Asp)	GHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
8652	NM_000163.5(GHR):c.484G>A (p.Val162Ile)	GHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1357046	NM_000163.5(GHR):c.895C>T (p.Pro299Ser)	GHR	Uncertain significance	criteria provided, multiple submitters, no conflicts
1486356	NM_000163.5(GHR):c.1214A>C (p.His405Pro)	GHR	Uncertain significance	criteria provided, multiple submitters, no conflicts
225374	NM_000163.5(GHR):c.497G>A (p.Gly166Glu)	GHR	Uncertain significance	criteria provided, multiple submitters, no conflicts
3009375	NM_000163.5(GHR):c.1262C>A (p.Ala421Glu)	GHR	Uncertain significance	criteria provided, multiple submitters, no conflicts
3099733	NM_000163.5(GHR):c.557G>C (p.Gly186Ala)	GHR	Uncertain significance	criteria provided, multiple submitters, no conflicts
3382732	NM_000163.5(GHR):c.669_674del (p.Asp223_Lys224del)	GHR	Uncertain significance	criteria provided, single submitter
3382733	NM_000163.5(GHR):c.1704del (p.Thr569fs)	GHR	Uncertain significance	criteria provided, single submitter
3382885	NM_000163.5(GHR):c.821G>A (p.Gly274Glu)	GHR	Uncertain significance	criteria provided, single submitter
353678	NM_000163.5(GHR):c.182G>A (p.Arg61Gln)	GHR	Uncertain significance	criteria provided, multiple submitters, no conflicts
353681	NM_000163.5(GHR):c.660G>T (p.Leu220Phe)	GHR	Uncertain significance	criteria provided, multiple submitters, no conflicts
3592691	NM_000163.5(GHR):c.431A>T (p.Asp144Val)	GHR	Uncertain significance	criteria provided, single submitter
3641427	NM_000163.5(GHR):c.1024T>C (p.Trp342Arg)	GHR	Uncertain significance	criteria provided, multiple submitters, no conflicts
3780857	NM_000163.5(GHR):c.-12+59281G>C	GHR	Uncertain significance	criteria provided, single submitter
3893116	NM_000163.5(GHR):c.1541G>A (p.Cys514Tyr)	GHR	Uncertain significance	criteria provided, single submitter
930323	NM_000163.5(GHR):c.1003G>A (p.Glu335Lys)	GHR	Uncertain significance	criteria provided, multiple submitters, no conflicts
931622	NM_000163.5(GHR):c.-12+643G>A	GHR	Uncertain significance	criteria provided, single submitter

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	Strong	Autosomal dominant	short stature due to partial GHR deficiency	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

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: 0.