isolated growth hormone deficiency type II

Summary

isolated growth hormone deficiency type II (MONDO:0008250) is a disease caused by GH1 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: GH1 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 29

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated growth hormone deficiency type II
Mondo ID	MONDO:0008250
MeSH	C562704
OMIM	173100
Orphanet	231679
DOID	DOID:0060872
SNOMED CT	237687003
UMLS	C0271567
MedGen	124405
GARD	0001696
Is cancer (heuristic)	no

Also known as: congenital IGHD type II · congenital isolated GH deficiency type II · congenital isolated growth hormone deficiency type II · Growth hormone deficiency, isolated autosomal dominant · growth hormone deficiency, isolated, type II · IGHD2 · isolated growth hormone deficiency type 2 · isolated growth hormone deficiency, type II · pituitary dwarfism due to isolated growth hormone deficiency autosomal dominant

Data availability: 29 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 II

Related subtypes (6): 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 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

29 retrieved; paginated sample, class counts are floors:

15 pathogenic, 7 uncertain significance, 3 benign/likely benign, 3 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
15970	NM_000515.5(GH1):c.291+1G>A	GH-LCR	Pathogenic	criteria provided, multiple submitters, no conflicts
15971	NM_000515.5(GH1):c.291+1G>C	GH-LCR	Pathogenic	criteria provided, multiple submitters, no conflicts
15973	NM_000515.5(GH1):c.291+29_291+46del	GH-LCR	Pathogenic	no assertion criteria provided
15977	NM_000515.5(GH1):c.176A>G (p.Glu59Gly)	GH-LCR	Pathogenic	no assertion criteria provided
15980	NM_000515.5(GH1):c.291+2T>C	GH-LCR	Pathogenic	criteria provided, single submitter
15982	NM_000515.5(GH1):c.292-37_292-16del	GH-LCR	Pathogenic	no assertion criteria provided
15968	NM_000515.5(GH1):c.291+6T>C	GH1	Pathogenic	no assertion criteria provided
15972	NM_000515.5(GH1):c.291+28G>A	GH1	Pathogenic	no assertion criteria provided
15975	NM_000515.5(GH1):c.291+5G>A	GH1	Pathogenic	criteria provided, multiple submitters, no conflicts
15979	NM_000515.5(GH1):c.172-2A>T	GH1	Pathogenic	no assertion criteria provided
15983	NM_000515.5(GH1):c.626G>A (p.Arg209His)	GH1	Pathogenic	criteria provided, multiple submitters, no conflicts
15984	NM_000515.5(GH1):c.173A>C (p.Glu58Ala)	GH1	Pathogenic	no assertion criteria provided
15985	NM_000515.5(GH1):c.172G>A (p.Glu58Lys)	GH1	Pathogenic/Likely pathogenic	no assertion criteria provided
2671898	NM_005121.3(MED13):c.1968-867_2181+479del	MED13	Pathogenic	criteria provided, single submitter
2672057	NM_005121.3(MED13):c.1968-866_2181+621del	MED13	Pathogenic	criteria provided, single submitter
2672058	NM_005121.3(MED13):c.1968-501_2181+590del	MED13	Pathogenic	criteria provided, single submitter
2671969	NM_000515.5(GH1):c.334T>C (p.Trp112Arg)	GH-LCR	Likely pathogenic	criteria provided, single submitter
1702861	NM_000515.5(GH1):c.254C>T (p.Pro85Leu)	GH1	Likely pathogenic	criteria provided, single submitter
998049	NM_000515.5(GH1):c.131A>C (p.His44Pro)	GH1	Likely pathogenic	no assertion criteria provided
1030835	NM_000515.5(GH1):c.302T>C (p.Leu101Pro)	GH-LCR	Uncertain significance	criteria provided, multiple submitters, no conflicts
324457	NM_000515.5(GH1):c.127G>A (p.Ala43Thr)	GH-LCR	Uncertain significance	criteria provided, multiple submitters, no conflicts
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
1679136	NM_000515.5(GH1):c.452T>C (p.Met151Thr)	GH1	Uncertain significance	criteria provided, single submitter
3370355	NM_000515.5(GH1):c.640_648del (p.Ser214_Gly216del)	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
195080	NM_000515.5(GH1):c.152T>A (p.Phe51Tyr)	GH1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 21 · Orphanet: 8 · 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
POU1F1	Definitive	Semidominant	pituitary hormone deficiency, combined, 1	10

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
POU1F1	Orphanet:226307	Hypothyroidism due to deficient transcription factors involved in pituitary development or function
POU1F1	Orphanet:231679	Isolated growth hormone deficiency type II
POU1F1	Orphanet:95494	Combined pituitary hormone deficiencies, genetic forms
MED13	Orphanet:528084	Non-specific syndromic intellectual disability

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GH1	HGNC:4261	ENSG00000259384	P01241	Somatotropin	gencc,clinvar
POU1F1	HGNC:9210	ENSG00000064835	P28069	Pituitary-specific positive transcription factor 1	gencc
MED13	HGNC:22474	ENSG00000108510	Q9UHV7	Mediator of RNA polymerase II transcription subunit 13	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.
POU1F1	Pituitary-specific positive transcription factor 1	Transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary.
MED13	Mediator of RNA polymerase II transcription subunit 13	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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
Transcription factor	1	2.8×	0.587
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GH1	Other/Unknown	no		Somatotropin/Prolactin, 4_helix_cytokine-like_core, Somatotropin_CS
POU1F1	Transcription factor	no		POU_dom, HD, Homeodomain-like_sf
MED13	Other/Unknown	no		Med13_C, MID_MedPIWI, Mediator_complx_sub13

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	2
pituitary gland	2
male germ line stem cell (sensu Vertebrata) in testis	1
decidua	1
endothelial cell	1
germinal epithelium of ovary	1
visceral pleura	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
POU1F1	73	tissue_specific	yes	pituitary gland, adenohypophysis, decidua
MED13	295	ubiquitous	marker	endothelial cell, visceral pleura, germinal epithelium of ovary

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MED13	1,956
POU1F1	1,170
GH1	1,007

Intra-cohort edges

A	B	Sources
GH1	POU1F1	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GH1	P01241	10
MED13	Q9UHV7	5
POU1F1	P28069	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 27. Enrichment computed across 3 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×	0.035	GH1
Synthesis, secretion, and deacylation of Ghrelin	1	300.5×	0.035	GH1
Growth hormone receptor signaling	1	237.9×	0.035	GH1
Peptide hormone metabolism	1	135.9×	0.035	GH1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1	107.7×	0.035	MED13
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1	98.5×	0.035	MED13
Respiratory Syncytial Virus Infection Pathway	1	98.5×	0.035	MED13
RSV-host interactions	1	78.2×	0.035	MED13
Adipogenesis	1	78.2×	0.035	MED13
Epigenetic regulation by WDR5-containing histone modifying complexes	1	77.2×	0.035	MED13
Regulation of lipid metabolism by PPARalpha	1	70.5×	0.035	MED13
Transcriptional regulation of white adipocyte differentiation	1	64.9×	0.035	MED13
PPARA activates gene expression	1	47.2×	0.044	MED13
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	41.4×	0.046	MED13
Epigenetic regulation of gene expression	1	35.7×	0.050	MED13
Cytokine Signaling in Immune system	1	20.4×	0.082	GH1
Metabolism of lipids	1	15.8×	0.096	MED13
Viral Infection Pathways	1	15.4×	0.096	MED13
Infectious disease	1	12.4×	0.112	MED13
RNA Polymerase II Transcription	1	11.3×	0.117	MED13
Gene expression (Transcription)	1	8.9×	0.140	MED13
Generic Transcription Pathway	1	7.5×	0.157	MED13
Developmental Biology	1	7.2×	0.157	MED13
Disease	1	6.5×	0.160	MED13
Immune System	1	6.5×	0.160	GH1
Metabolism of proteins	1	6.2×	0.161	GH1
Metabolism	1	5.8×	0.165	MED13

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
bone maturation	1	1872.4×	0.010	GH1
adenohypophysis development	1	802.5×	0.010	POU1F1
positive regulation of D-glucose transmembrane transport	1	702.2×	0.010	GH1
growth hormone receptor signaling pathway via JAK-STAT	1	510.7×	0.010	GH1
positive regulation of insulin-like growth factor receptor signaling pathway	1	401.2×	0.010	GH1
growth hormone receptor signaling pathway	1	401.2×	0.010	GH1
animal organ development	1	244.2×	0.015	GH1
cell surface receptor signaling pathway via STAT	1	187.2×	0.016	GH1
positive regulation of multicellular organism growth	1	165.2×	0.016	GH1
triglyceride homeostasis	1	160.5×	0.016	MED13
positive regulation of receptor signaling pathway via JAK-STAT	1	144.0×	0.016	GH1
response to nutrient levels	1	122.1×	0.017	GH1
negative regulation of transcription by RNA polymerase II	2	11.8×	0.018	MED13, POU1F1
cell surface receptor signaling pathway via JAK-STAT	1	96.8×	0.018	GH1
positive regulation of transcription initiation by RNA polymerase II	1	90.6×	0.018	MED13
positive regulation of transcription by RNA polymerase II	2	9.9×	0.020	MED13, POU1F1
response to estradiol	1	66.1×	0.022	GH1
cholesterol homeostasis	1	52.0×	0.027	MED13
cytokine-mediated signaling pathway	1	43.5×	0.030	GH1
positive regulation of MAPK cascade	1	26.9×	0.045	GH1
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	26.1×	0.045	GH1
negative regulation of cell population proliferation	1	14.0×	0.079	POU1F1
regulation of DNA-templated transcription	1	10.5×	0.100	POU1F1
positive regulation of DNA-templated transcription	1	9.3×	0.108	MED13
regulation of transcription by RNA polymerase II	1	3.9×	0.236	POU1F1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 evidence-associated genes (0%) 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
POU1F1	0	0
MED13	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	GH1, POU1F1, MED13

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GH1	0	—
POU1F1	0	—
MED13	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.