isolated growth hormone deficiency type IB

Summary

isolated growth hormone deficiency type IB (MONDO:0013006) is a disease caused by GHRHR (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: GHRHR (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 64

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated growth hormone deficiency type IB
Mondo ID	MONDO:0013006
MeSH	C567564
OMIM	612781
Orphanet	231671
DOID	DOID:0060874
UMLS	C2748571
MedGen	411242
GARD	0003919
Is cancer (heuristic)	no

Also known as: congenital IGHD type IB · congenital isolated GH deficiency type IB · congenital isolated growth hormone deficiency type IB · dwarfism of Sindh · growth hormone deficiency, isolated, type IB · IGHD 1B · IGHD1B · isolated growth hormone deficiency type 1B · isolated growth hormone deficiency, type IB

Data availability: 64 ClinVar variants · 3 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 IB

Related subtypes (6): isolated growth hormone deficiency type II, isolated growth hormone deficiency type IA, short stature due to growth hormone qualitative anomaly, isolated growth hormone deficiency type III, 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

64 retrieved; paginated sample, class counts are floors:

23 uncertain significance, 17 conflicting classifications of pathogenicity, 9 benign, 6 pathogenic, 3 benign/likely benign, 3 likely benign, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
88740	NC_000007.14:g.62535490A>G		Pathogenic	no assertion criteria provided
15967	NM_000515.5(GH1):c.456+1G>T	GH-LCR	Pathogenic	no assertion criteria provided
15970	NM_000515.5(GH1):c.291+1G>A	GH-LCR	Pathogenic	criteria provided, multiple submitters, no conflicts
15976	NM_000515.5(GH1):c.456+5G>C	GH-LCR	Pathogenic	no assertion criteria provided
161436	NM_000823.4(GHRHR):c.281G>A (p.Arg94Gln)	GHRHR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56966	NC_000007.14:g.30959635_30967328delinsAGAGATCCA	GHRHR	Pathogenic	no assertion criteria provided
626257	NC_000007.14:g.31008681G>T	GHRHR	Pathogenic	no assertion criteria provided
161435	NM_000823.4(GHRHR):c.418T>C (p.Ser140Pro)	GHRHR	Likely pathogenic	no assertion criteria provided
161437	NM_000823.4(GHRHR):c.495C>A (p.His165Gln)	GHRHR	Likely pathogenic	no assertion criteria provided
198104	NM_000823.4(GHRHR):c.489C>T (p.Tyr163=)	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
284569	NM_000823.4(GHRHR):c.741C>T (p.Leu247=)	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
287138	NM_000823.4(GHRHR):c.512C>G (p.Thr171Ser)	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
360034	NM_000823.4(GHRHR):c.812+12C>T	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
597235	NM_000823.4(GHRHR):c.660G>A (p.Leu220=)	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
729746	NM_000823.4(GHRHR):c.975-6C>A	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
749584	NM_000823.4(GHRHR):c.93C>T (p.Ile31=)	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909042	NM_000823.4(GHRHR):c.47C>T (p.Pro16Leu)	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909045	NM_000823.4(GHRHR):c.200C>T (p.Thr67Met)	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909104	NM_000823.4(GHRHR):c.1105-14C>G	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909106	NM_000823.4(GHRHR):c.1242G>A (p.Ser414=)	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909902	NM_000823.4(GHRHR):c.237G>A (p.Pro79=)	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909905	NM_000823.4(GHRHR):c.359C>T (p.Ala120Val)	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
910805	NM_000823.4(GHRHR):c.490G>A (p.Val164Ile)	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
910807	NM_000823.4(GHRHR):c.580C>T (p.His194Tyr)	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
911972	NM_000823.4(GHRHR):c.6C>T (p.Asp2=)	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
912020	NM_000823.4(GHRHR):c.751+12G>A	GHRHR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
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
892518	NM_000515.5(GH1):c.350A>G (p.Gln117Arg)	GH-LCR	Uncertain significance	criteria provided, multiple submitters, no conflicts
3582622	NM_000515.5(GH1):c.346G>A (p.Val116Met)	GH1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 5 · 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
GHRHR	Definitive	Autosomal recessive	isolated growth hormone deficiency type IB	4

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
GHRHR	Orphanet:684247	Isolated growth hormone deficiency type IV

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GH1	HGNC:4261	ENSG00000259384	P01241	Somatotropin	gencc,clinvar
GHRHR	HGNC:4266	ENSG00000106128	Q02643	Growth hormone-releasing hormone receptor	gencc,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.
GHRHR	Growth hormone-releasing hormone receptor	Receptor for GRF, coupled to G proteins which activate adenylyl cyclase.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
GPCR	1	12.0×	0.164
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GH1	Other/Unknown	no		Somatotropin/Prolactin, 4_helix_cytokine-like_core, Somatotropin_CS
GHRHR	GPCR	yes		GPCR_2_secretin-like, GPCR_2_extracellular_dom, GPCR_2_GHRH_rcpt

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	2
pituitary gland	2
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	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
GHRHR	154	broad	marker	pituitary gland, adenohypophysis, oocyte

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GHRHR	1,047
GH1	1,007

Intra-cohort edges

A	B	Sources
GH1	GHRHR	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GH1	P01241	10
GHRHR	Q02643	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 2 evidence-associated genes (2 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 2 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	380.7×	0.013	GH1
Synthesis, secretion, and deacylation of Ghrelin	1	300.5×	0.013	GH1
Growth hormone receptor signaling	1	237.9×	0.013	GH1
Glucagon-type ligand receptors	1	173.0×	0.013	GHRHR
Peptide hormone metabolism	1	135.9×	0.013	GH1
G alpha (s) signalling events	1	36.6×	0.041	GHRHR
Cytokine Signaling in Immune system	1	20.4×	0.062	GH1
Immune System	1	6.5×	0.155	GH1
Metabolism of proteins	1	6.2×	0.155	GH1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of insulin-like growth factor receptor signaling pathway	2	1203.7×	2e-05	GH1, GHRHR
positive regulation of multicellular organism growth	2	495.6×	7e-05	GH1, GHRHR
regulation of intracellular steroid hormone receptor signaling pathway	1	8426.0×	0.001	GHRHR
somatotropin secreting cell development	1	8426.0×	0.001	GHRHR
bone maturation	1	2808.7×	0.002	GH1
positive regulation of circadian sleep/wake cycle, non-REM sleep	1	2106.5×	0.003	GHRHR
growth hormone secretion	1	1404.3×	0.004	GHRHR
positive regulation of D-glucose transmembrane transport	1	1053.2×	0.004	GH1
regulation of protein metabolic process	1	1053.2×	0.004	GHRHR
positive regulation of growth hormone secretion	1	936.2×	0.004	GHRHR
growth hormone receptor signaling pathway via JAK-STAT	1	766.0×	0.004	GH1
cAMP/PKA signal transduction	1	702.2×	0.004	GHRHR
growth hormone receptor signaling pathway	1	601.9×	0.004	GH1
hormone metabolic process	1	443.5×	0.006	GHRHR
animal organ development	1	366.4×	0.006	GH1
cell surface receptor signaling pathway via STAT	1	280.9×	0.008	GH1
cell maturation	1	221.7×	0.008	GHRHR
determination of adult lifespan	1	216.1×	0.008	GHRHR
positive regulation of receptor signaling pathway via JAK-STAT	1	216.1×	0.008	GH1
lactation	1	210.7×	0.008	GHRHR
response to nutrient levels	1	183.2×	0.009	GH1
response to estrogen	1	172.0×	0.009	GHRHR
response to glucocorticoid	1	162.0×	0.009	GHRHR
cell surface receptor signaling pathway via JAK-STAT	1	145.3×	0.010	GH1
cellular response to glucose stimulus	1	133.8×	0.010	GHRHR
response to insulin	1	115.4×	0.012	GHRHR
response to estradiol	1	99.1×	0.013	GH1
cellular response to insulin stimulus	1	85.1×	0.015	GHRHR
establishment of localization in cell	1	80.2×	0.015	GHRHR
cytokine-mediated signaling pathway	1	65.3×	0.018	GH1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
GHRHR	DOCETAXEL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GHRHR	1	4
GH1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DOCETAXEL	4	GHRHR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GHRHR	3	Binding:3

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 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)
DOCETAXEL	4	GHRHR

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GHRHR
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	1	GH1

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)
GH1	0	GHRHR

Clinical trials & evidence

Clinical trials

Clinical trials: 0.