IGHD2
MCID: ISL114
MIFTS: 47

Isolated Growth Hormone Deficiency, Type Ii (IGHD2)

Categories: Endocrine diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Isolated Growth Hormone Deficiency, Type Ii

MalaCards integrated aliases for Isolated Growth Hormone Deficiency, Type Ii:

Name: Isolated Growth Hormone Deficiency, Type Ii 58 74
Isolated Growth Hormone Deficiency Type Ii 12 54 60 76 15
Ighd Ii 58 12 54 76 56
Growth Hormone Deficiency, Isolated, Type Ii 58 13 41
Ighd2 58 54 76
Pituitary Dwarfism Due to Isolated Growth Hormone Deficiency Autosomal Dominant 54 76
Congenital Isolated Growth Hormone Deficiency Type Ii 12 60
Congenital Isolated Gh Deficiency Type Ii 12 60
Congenital Ighd Type Ii 12 60
Pituitary Dwarfism Due to Isolated Growth Hormone Deficiency, Autosomal Dominant 58
Autosomal Dominant Pituitary Dwarfism Due to Isolated Growth Hormone Deficiency 12
Growth Hormone Deficiency, Isolated, Autosomal Dominant 58
Growth Hormone Deficiency, Isolated Autosomal Dominant 54
Autosomal Dominant Isolated Growth Hormone Deficiency 12
Growth Hormone Deficiency Isolated Autosomal Dominant 76
Isolated Growth Hormone Deficiency Type 2 54
Growth Hormone Deficiency, Isolated, 2 76

Characteristics:

Orphanet epidemiological data:

60
isolated growth hormone deficiency type ii
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal dominant form


HPO:

33
isolated growth hormone deficiency, type ii:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 60  
Rare endocrine diseases


External Ids:

Disease Ontology 12 DOID:0060872
OMIM 58 173100
MeSH 45 D004393
ICD10 34 E23.0
ICD10 via Orphanet 35 E23.0
UMLS via Orphanet 75 C0271567
Orphanet 60 ORPHA231679
MedGen 43 C0271567
UMLS 74 C0271567

Summaries for Isolated Growth Hormone Deficiency, Type Ii

OMIM : 58 Type II IGHD is an autosomal dominant disorder characterized by low but detectable levels of growth hormone (GH), variable height deficit and age at presentation, and good response to rhGH. Patients may show anterior pituitary hypoplasia on MRI (summary by Phillips and Cogan, 1994; Alatzoglou and Dattani, 2012). (173100)

MalaCards based summary : Isolated Growth Hormone Deficiency, Type Ii, also known as isolated growth hormone deficiency type ii, is related to isolated growth hormone deficiency and growth hormone deficiency. An important gene associated with Isolated Growth Hormone Deficiency, Type Ii is GH1 (Growth Hormone 1), and among its related pathways/superpathways are Pathways in cancer and Prolactin Signaling Pathway. Affiliated tissues include pituitary, myeloid and b cells, and related phenotypes are severe short stature and growth hormone deficiency

Disease Ontology : 12 An isolated growth hormone deficiency characterized by autosomal dominant inheritance of low but detectable levels of GH1 resulting in variable degrees of dwarfism which are responsive to growth hormone therapy that has material basis in dominant negative mutations in the GH1 gene on chromosome 17q23.3.

UniProtKB/Swiss-Prot : 76 Growth hormone deficiency, isolated, 2: An autosomal dominant deficiency of growth hormone leading to short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy.

Related Diseases for Isolated Growth Hormone Deficiency, Type Ii

Diseases related to Isolated Growth Hormone Deficiency, Type Ii via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 39)
# Related Disease Score Top Affiliating Genes
1 isolated growth hormone deficiency 32.2 GH1 GHR GHRH GHRHR HESX1 IGF1
2 growth hormone deficiency 30.7 GH1 GHRH GHRHR HESX1 IGF1
3 non-functioning pituitary adenoma 10.4 GH1 GHR
4 hypothyroidism due to deficient transcription factors involved in pituitary development or function 10.3 HESX1 POU1F1
5 pseudohypoparathyroidism, type ia 10.3 GH1 IGF1
6 combined pituitary hormone deficiencies, genetic forms 10.3 HESX1 POU1F1
7 hypothyroidism, congenital, nongoitrous, 4 10.3 GH1 IGF1 POU1F1
8 hypothalamic disease 10.3 GH1 GHRH
9 pituitary tumors 10.3 GH1 IGF1 POU1F1
10 craniopharyngioma 10.3 GH1 IGF1 POU1F1
11 central precocious puberty 10.3 GH1 IGF1
12 pituitary hypoplasia 10.2 GHRHR HESX1 POU1F1
13 turner syndrome 10.2 GH1 GHR IGF1
14 pituitary hormone deficiency, combined, 1 10.2 HESX1 POU1F1
15 gigantism 10.2 GH1 GHRH
16 hyperpituitarism 10.2 GH1 GHR GHRH IGF1
17 dwarfism 10.2 GH1 GHR GHRH GHRHR
18 empty sella syndrome 10.2 GH1 IGF1
19 pituitary stalk interruption syndrome 10.2 GH1 GHRHR HESX1 POU1F1
20 acromegaly 10.2 GH1 GHR GHRH IGF1
21 insulin-like growth factor i 10.2 GH1 GHR GHRH IGF1
22 anorexia nervosa 10.1 GH1 GHR GHRH IGF1
23 laron syndrome 10.1 GH1 GHR IGF1 STAT5B
24 hypothyroidism 10.1 GH1 HESX1 IGF1 POU1F1
25 isolated growth hormone deficiency type iii 10.1 ESX1 HESX1
26 isolated growth hormone deficiency, type ib 10.1 GH1 GHR GHRH GHRHR IGF1
27 marasmus 10.0 GH1 IGF1
28 pituitary hormone deficiency, combined, 2 10.0 GH1 GHR HESX1 IGF1 POU1F1
29 pituitary gland disease 10.0 GH1 GHRH HESX1 IGF1 POU1F1
30 hypopituitarism 10.0 GH1 GHRH HESX1 IGF1 POU1F1
31 b cell linker protein deficiency 9.9 STAT5A STAT5B
32 cellular congenital mesoblastic nephroma 9.9 STAT5A STAT5B
33 body mass index quantitative trait locus 11 9.9 GH1 GHR GHRH IGF1 JAK2
34 erythrocytosis, familial, 1 9.8 JAK2 STAT5A STAT5B
35 jak3-deficient severe combined immunodeficiency 9.8 STAT5A STAT5B
36 chronic leukemia 9.7 JAK2 SRSF2 STAT5A STAT5B
37 myelofibrosis 9.7 JAK2 SRSF2 STAT5A STAT5B
38 leukemia, chronic myeloid 9.6 ANXA5 JAK2 STAT5A STAT5B
39 leukemia, acute myeloid 9.5 ANXA5 JAK2 SRSF2 STAT5A STAT5B

Graphical network of the top 20 diseases related to Isolated Growth Hormone Deficiency, Type Ii:



Diseases related to Isolated Growth Hormone Deficiency, Type Ii

Symptoms & Phenotypes for Isolated Growth Hormone Deficiency, Type Ii

Human phenotypes related to Isolated Growth Hormone Deficiency, Type Ii:

33
# Description HPO Frequency HPO Source Accession
1 severe short stature 33 HP:0003510
2 growth hormone deficiency 33 HP:0000824
3 pituitary dwarfism 33 HP:0000839

Symptoms via clinical synopsis from OMIM:

58
Growth:
dwarfism

Lab:
insulin responses to glucose and to arginine usually greater than normal
no insulinopenia

Endocrine:
isolated growth hormone deficiency

Clinical features from OMIM:

173100

GenomeRNAi Phenotypes related to Isolated Growth Hormone Deficiency, Type Ii according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 no effect GR00402-S-1 9.92 ANXA5 ELF3 ELF5 ESX1 GH1 GHR

MGI Mouse Phenotypes related to Isolated Growth Hormone Deficiency, Type Ii:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.13 ELF3 GHR GHRH GHRHR HESX1 HSP90B1
2 endocrine/exocrine gland MP:0005379 10.11 GHR GHRH GHRHR HESX1 HTRA2 IGF1
3 hematopoietic system MP:0005397 10 ANXA5 GHR GHRHR HSP90B1 HTRA2 IGF1
4 immune system MP:0005387 9.93 ANXA5 GHR GHRH GHRHR HSP90B1 HTRA2
5 adipose tissue MP:0005375 9.88 GHR GHRHR HTRA2 IGF1 STAT5A STAT5B
6 integument MP:0010771 9.5 GHR GHRHR HTRA2 IGF1 JAK2 STAT5A
7 mortality/aging MP:0010768 9.47 ELF3 GHR GOSR2 HESX1 HSP90B1 HTRA2

Drugs & Therapeutics for Isolated Growth Hormone Deficiency, Type Ii

Search Clinical Trials , NIH Clinical Center for Isolated Growth Hormone Deficiency, Type Ii

Genetic Tests for Isolated Growth Hormone Deficiency, Type Ii

Anatomical Context for Isolated Growth Hormone Deficiency, Type Ii

MalaCards organs/tissues related to Isolated Growth Hormone Deficiency, Type Ii:

42
Pituitary, Myeloid, B Cells

Publications for Isolated Growth Hormone Deficiency, Type Ii

Articles related to Isolated Growth Hormone Deficiency, Type Ii:

(show all 24)
# Title Authors Year
1
Isolated Growth Hormone Deficiency Type II due to a novel GH1 mutation: A Case Report ( 30678423 )
2019
2
Splice site mutations in GH1 detected in previously (Genetically) undiagnosed families with congenital isolated growth hormone deficiency type II. ( 24280736 )
2013
3
A novel GH1 mutation in a family with isolated growth hormone deficiency type II. ( 22188748 )
2012
4
A molecular basis for variation in clinical severity of isolated growth hormone deficiency type II. ( 19837935 )
2009
5
Rescue of pituitary function in a mouse model of isolated growth hormone deficiency type II by RNA interference. ( 18006625 )
2008
6
Isolated growth hormone deficiency type II caused by a point mutation that alters both splice site strength and splicing enhancer function. ( 18554279 )
2008
7
Exon splice enhancer mutation (GH-E32A) causes autosomal dominant growth hormone deficiency. ( 17726075 )
2007
8
Variable phenotypes in familial isolated growth hormone deficiency caused by a G6664A mutation in the GH-1 gene. ( 17785368 )
2007
9
Mutant and misfolded human growth hormone is rapidly degraded through the proteasomal degradation pathway in a cellular model for isolated growth hormone deficiency type II. ( 17927666 )
2007
10
A novel deletion in the GH1 gene including the IVS3 branch site responsible for autosomal dominant isolated growth hormone deficiency. ( 16368751 )
2006
11
A novel IVS2 -2A>T splicing mutation in the GH-1 gene in familial isolated growth hormone deficiency type II in the spectrum of other splicing mutations in the Russian population. ( 12574219 )
2003
12
An exonic mutation of the GH-1 gene causing familial isolated growth hormone deficiency type II. ( 12000366 )
2002
13
An exon splice enhancer mutation causes autosomal dominant GH deficiency. ( 11836331 )
2002
14
A Japanese family with autosomal dominant growth hormone deficiency. ( 10445339 )
1999
15
Inhibition of growth hormone (GH) secretion by a mutant GH-I gene product in neuroendocrine cells containing secretory granules: an implication for isolated GH deficiency inherited in an autosomal dominant manner. ( 10372722 )
1999
16
Mutations in intron 3 of GH-1 gene associated with isolated GH deficiency type II in three Japanese families. ( 10469016 )
1999
17
Characterization of an intron splice enhancer that regulates alternative splicing of human GH pre-mRNA. ( 9700205 )
1998
18
Genetic defects in the control of growth hormone secretion. ( 9554464 )
1998
19
A novel mechanism of aberrant pre-mRNA splicing in humans. ( 9175738 )
1997
20
Mechanisms responsible for dominant expression of human growth hormone gene mutations. ( 8923859 )
1996
21
A recurring dominant negative mutation causes autosomal dominant growth hormone deficiency--a clinical research center study. ( 8530604 )
1995
22
Screening for growth hormone (GH) gene splice-site mutations in sporadic cases with severe isolated GH deficiency using ectopic transcript analysis. ( 7714096 )
1995
23
An intronic (A/U)GGG repeat enhances the splicing of an alternative intron of the chicken beta-tropomyosin pre-mRNA. ( 7567462 )
1995
24
Isolated growth hormone deficiency, type II (sexual ateleiosis, type II). ( 5173170 )
1971

Variations for Isolated Growth Hormone Deficiency, Type Ii

UniProtKB/Swiss-Prot genetic disease variations for Isolated Growth Hormone Deficiency, Type Ii:

76
# Symbol AA change Variation ID SNP ID
1 GH1 p.Arg209His VAR_015815 rs137853223

ClinVar genetic disease variations for Isolated Growth Hormone Deficiency, Type Ii:

6 (show all 26)
# Gene Variation Type Significance SNP ID Assembly Location
1 GH1 NM_000515.4(GH1): c.291+6T> C single nucleotide variant Pathogenic rs797044450 GRCh37 Chromosome 17, 61995371: 61995371
2 GH1 NM_000515.4(GH1): c.291+6T> C single nucleotide variant Pathogenic rs797044450 GRCh38 Chromosome 17, 63918011: 63918011
3 GH1 NM_000515.4(GH1): c.291+1G> A single nucleotide variant Pathogenic rs71640277 GRCh38 Chromosome 17, 63918016: 63918016
4 GH1 NM_000515.4(GH1): c.291+1G> A single nucleotide variant Pathogenic rs71640277 GRCh37 Chromosome 17, 61995376: 61995376
5 GH1 NM_000515.4(GH1): c.291+1G> C single nucleotide variant Pathogenic rs71640277 GRCh37 Chromosome 17, 61995376: 61995376
6 GH1 NM_000515.4(GH1): c.291+1G> C single nucleotide variant Pathogenic rs71640277 GRCh38 Chromosome 17, 63918016: 63918016
7 GH1 NM_000515.4(GH1): c.291+28G> A single nucleotide variant Pathogenic rs863223306 GRCh37 Chromosome 17, 61995349: 61995349
8 GH1 NM_000515.4(GH1): c.291+28G> A single nucleotide variant Pathogenic rs863223306 GRCh38 Chromosome 17, 63917989: 63917989
9 GH1 GH1, IVS3, 18-BP DEL, +28-45 deletion Pathogenic
10 GH1 NM_000515.4(GH1): c.291+5G> A single nucleotide variant Pathogenic rs863223307 GRCh38 Chromosome 17, 63918012: 63918012
11 GH1 NM_000515.4(GH1): c.291+5G> A single nucleotide variant Pathogenic rs863223307 GRCh37 Chromosome 17, 61995372: 61995372
12 GH1 GH1, EX3, A-G, +5 single nucleotide variant Pathogenic
13 GH1 GH1, EX3DEL deletion Pathogenic
14 GH1 NM_000515.4(GH1): c.172-2A> T single nucleotide variant Pathogenic rs863223309 GRCh37 Chromosome 17, 61995498: 61995498
15 GH1 NM_000515.4(GH1): c.172-2A> T single nucleotide variant Pathogenic rs863223309 GRCh38 Chromosome 17, 63918138: 63918138
16 GH1 NM_000515.4(GH1): c.291+2T> C single nucleotide variant Pathogenic rs863223310 GRCh37 Chromosome 17, 61995375: 61995375
17 GH1 NM_000515.4(GH1): c.291+2T> C single nucleotide variant Pathogenic rs863223310 GRCh38 Chromosome 17, 63918015: 63918015
18 GH1 GH1, IVS3, 22-BP DEL deletion Pathogenic
19 GH1 NM_000515.4(GH1): c.626G> A (p.Arg209His) single nucleotide variant Pathogenic rs137853223 GRCh37 Chromosome 17, 61994697: 61994697
20 GH1 NM_000515.4(GH1): c.626G> A (p.Arg209His) single nucleotide variant Pathogenic rs137853223 GRCh38 Chromosome 17, 63917337: 63917337
21 GH1 GH1, EX3, A-C, +2 single nucleotide variant Pathogenic
22 GH1 GH1, EX3, G-A, +1 single nucleotide variant Pathogenic
23 GH1 NM_000515.4(GH1): c.7A> G (p.Thr3Ala) single nucleotide variant Benign rs2001345 GRCh37 Chromosome 17, 61996130: 61996130
24 GH1 NM_000515.4(GH1): c.7A> G (p.Thr3Ala) single nucleotide variant Benign rs2001345 GRCh38 Chromosome 17, 63918770: 63918770
25 GH1 NM_000515.4(GH1): c.-4T> G single nucleotide variant Benign/Likely benign rs6173 GRCh38 Chromosome 17, 63918780: 63918780
26 GH1 NM_000515.4(GH1): c.-4T> G single nucleotide variant Benign/Likely benign rs6173 GRCh37 Chromosome 17, 61996140: 61996140

Expression for Isolated Growth Hormone Deficiency, Type Ii

Search GEO for disease gene expression data for Isolated Growth Hormone Deficiency, Type Ii.

Pathways for Isolated Growth Hormone Deficiency, Type Ii

Pathways related to Isolated Growth Hormone Deficiency, Type Ii according to GeneCards Suite gene sharing:

(show all 25)
# Super pathways Score Top Affiliating Genes
1 12.71 HSP90B1 IGF1 JAK2 STAT5A STAT5B
2
Show member pathways
12.22 ELF5 GH1 JAK2 STAT5A STAT5B
3
Show member pathways
12.17 GH1 GHR JAK2 STAT5A STAT5B
4
Show member pathways
12.04 HSP90B1 IGF1 JAK2 STAT5A STAT5B
5 11.97 JAK2 RAB3A STAT5A STAT5B
6 11.9 ESX1 HESX1 IGF1 JAK2
7 11.85 GH1 IGF1 STAT5A STAT5B
8
Show member pathways
11.82 JAK2 STAT5A STAT5B
9 11.78 JAK2 STAT5A STAT5B
10 11.77 JAK2 STAT5A STAT5B
11
Show member pathways
11.76 JAK2 STAT5A STAT5B
12 11.67 POU1F1 STAT5A STAT5B
13 11.63 JAK2 STAT5A STAT5B
14 11.56 JAK2 STAT5A STAT5B
15 11.53 JAK2 STAT5A STAT5B
16 11.42 JAK2 STAT5A STAT5B
17 11.38 JAK2 STAT5A STAT5B
18 11.31 HSP90B1 STAT5A STAT5B
19 11.27 JAK2 STAT5A STAT5B
20
Show member pathways
11.24 JAK2 STAT5A STAT5B
21 11.16 JAK2 STAT5A STAT5B
22 11.07 GH1 GHR IGF1 STAT5B
23
Show member pathways
10.96 JAK2 STAT5A STAT5B
24
Show member pathways
10.63 GH1 GHR JAK2 STAT5A STAT5B
25 10.61 JAK2 STAT5A STAT5B

GO Terms for Isolated Growth Hormone Deficiency, Type Ii

Cellular components related to Isolated Growth Hormone Deficiency, Type Ii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endosome lumen GO:0031904 8.96 GH1 JAK2
2 growth hormone receptor complex GO:0070195 8.62 GH1 GHR

Biological processes related to Isolated Growth Hormone Deficiency, Type Ii according to GeneCards Suite gene sharing:

(show all 28)
# Name GO ID Score Top Affiliating Genes
1 cytokine-mediated signaling pathway GO:0019221 9.91 GHR HSP90B1 JAK2 STAT5A STAT5B
2 positive regulation of peptidyl-tyrosine phosphorylation GO:0050731 9.78 GH1 GHR IGF1 JAK2
3 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.77 GH1 IGF1 JAK2
4 positive regulation of tyrosine phosphorylation of STAT protein GO:0042531 9.76 GH1 GHR IGF1 JAK2
5 lactation GO:0007595 9.72 GHRHR STAT5A STAT5B
6 determination of adult lifespan GO:0008340 9.63 GHRHR POU1F1
7 hormone metabolic process GO:0042445 9.63 GHR GHRHR
8 insulin-like growth factor receptor signaling pathway GO:0048009 9.62 GHR IGF1
9 interleukin-15-mediated signaling pathway GO:0035723 9.62 STAT5A STAT5B
10 JAK-STAT cascade GO:0007259 9.62 GHR JAK2 STAT5A STAT5B
11 interleukin-2-mediated signaling pathway GO:0038110 9.61 STAT5A STAT5B
12 positive regulation of hormone secretion GO:0046887 9.61 GHRH GHRHR
13 growth hormone receptor signaling pathway GO:0060396 9.61 GH1 GHR JAK2
14 interleukin-9-mediated signaling pathway GO:0038113 9.59 STAT5A STAT5B
15 positive regulation of growth hormone secretion GO:0060124 9.58 GHRH GHRHR
16 growth hormone secretion GO:0030252 9.58 GHRH GHRHR
17 adenohypophysis development GO:0021984 9.58 GHRH GHRHR POU1F1
18 activation of Janus kinase activity GO:0042976 9.57 GHR JAK2
19 positive regulation of insulin-like growth factor receptor signaling pathway GO:0043568 9.56 GH1 GHRH GHRHR IGF1
20 regulation of multicellular organism growth GO:0040014 9.55 GHR HTRA2 IGF1 STAT5A STAT5B
21 regulation of insulin-like growth factor receptor signaling pathway GO:0043567 9.54 GHRHR POU1F1
22 taurine metabolic process GO:0019530 9.54 GHR STAT5A STAT5B
23 somatotropin secreting cell development GO:0060133 9.49 GHRHR POU1F1
24 JAK-STAT cascade involved in growth hormone signaling pathway GO:0060397 9.35 GH1 GHR JAK2 STAT5A STAT5B
25 positive regulation of circadian sleep/wake cycle, non-REM sleep GO:0046010 9.26 GHRHR
26 positive regulation of multicellular organism growth GO:0040018 9.1 GH1 GHR GHRH GHRHR POU1F1 STAT5B
27 regulation of transcription, DNA-templated GO:0006355 10.18 ELF3 ELF5 ESX1 HESX1 POU1F1 STAT5A
28 positive regulation of cell proliferation GO:0008284 10 GHRH GHRHR IGF1 JAK2 POU1F1 STAT5B

Molecular functions related to Isolated Growth Hormone Deficiency, Type Ii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.87 ELF3 ELF5 ESX1 HESX1 POU1F1 STAT5A
2 sequence-specific DNA binding GO:0043565 9.77 ELF3 ELF5 ESX1 HESX1 POU1F1
3 hormone activity GO:0005179 9.26 GH1 IGF1
4 peptide hormone receptor binding GO:0051428 9.16 GHRH JAK2
5 growth hormone receptor binding GO:0005131 8.96 GH1 JAK2
6 peptide hormone binding GO:0017046 8.8 ANXA5 GHR GHRHR

Sources for Isolated Growth Hormone Deficiency, Type Ii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
Content
Loading form....