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LARS
MCID: LRN002
MIFTS: 62

Laron Syndrome (LARS)

Categories: Endocrine diseases, Genetic diseases, Metabolic diseases, Muscle diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Laron Syndrome

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MalaCards integrated aliases for Laron Syndrome:

Name: Laron Syndrome 57 12 20 43 58 72 36 54 44 15 39 70
Growth Hormone Insensitivity Syndrome 57 20 43 58 72
Growth Hormone Receptor Deficiency 57 20 43 58 72
Laron Dwarfism 57 20 43 72 13
Laron-Type Isolated Somatotropin Defect 12 43 29 6
Pituitary Dwarfism Ii 57 20 43 72
Primary Growth Hormone Resistance 20 43 58
Laron-Type Dwarfism 73 43 58
Primary Growth Hormone Insensitivity 20 58
Laron Type Pituitary Dwarfism I 20 72
Primary Gh Resistance 43 58
Short Stature Due to a Defect in Growth Hormone Receptor or Post-Receptor Pathway 58
Short Stature Due to Growth Hormone Resistance 58
Complete Growth Hormone Insensitivity 58
Growth Hormone Receptor Defect 43
Laron-Type Pituitary Dwarfism 43
Laron-Type Short Stature 43
Primary Gh Insensitivity 58
Severe Gh Insensitivity 43
Gh Receptor Deficiency 58
Gh-R Deficiency 43
Ghis 58
Lars 72

Characteristics:

Orphanet epidemiological data:

58
laron syndrome
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
distorted sex ratio (19f:2m) in loja province ecuador cases.


HPO:

31
laron syndrome:
Inheritance autosomal recessive inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases
Anatomical: Endocrine diseases Muscle diseases
See all MalaCards categories (disease lists)
ICD10: 32 33
Orphanet: 58  
Rare endocrine diseases


Sources

Summaries for Laron Syndrome

About this section
MedlinePlus Genetics : 43 Laron syndrome is a rare form of short stature that results from the body's inability to use growth hormone, a substance produced by the brain's pituitary gland that helps promote growth. Affected individuals are close to normal size at birth, but they experience slow growth from early childhood that results in very short stature. If the condition is not treated, adult males typically reach a maximum height of about 4.5 feet; adult females may be just over 4 feet tall.Other features of untreated Laron syndrome include reduced muscle strength and endurance, low blood sugar levels (hypoglycemia) in infancy, small genitals and delayed puberty, hair that is thin and fragile, and dental abnormalities. Many affected individuals have a distinctive facial appearance, including a protruding forehead, a sunken bridge of the nose (saddle nose), and a blue tint to the whites of the eyes (blue sclerae). Affected individuals have short limbs compared to the size of their torso, as well as small hands and feet. Adults with this condition tend to develop obesity. However, the signs and symptoms of Laron syndrome vary, even among affected members of the same family.Studies suggest that people with Laron syndrome have a significantly reduced risk of cancer and type 2 diabetes. Affected individuals appear to develop these common diseases much less frequently than their unaffected relatives, despite having obesity (a risk factor for both cancer and type 2 diabetes). However, people with Laron syndrome do not seem to have an increased lifespan compared with their unaffected relatives.

MalaCards based summary : Laron Syndrome, also known as growth hormone insensitivity syndrome, is related to dwarfism and insulin-like growth factor i. An important gene associated with Laron Syndrome is GHR (Growth Hormone Receptor), and among its related pathways/superpathways are Neuroactive ligand-receptor interaction and Cytokine-cytokine receptor interaction. The drugs Mecasermin and Hormones have been mentioned in the context of this disorder. Affiliated tissues include pituitary, bone and liver, and related phenotypes are failure to thrive and delayed skeletal maturation

Disease Ontology : 12 A syndrome characterized by marked short stature with normal or high serum growth hormone and low serum insulin-like growth factor-1 levels that has material basis in homozygous or compound heterozygous mutation in GHR on chromosome 5p13-p12.

GARD : 20 Laron syndrome is a condition that occurs when the body is unable to utilize growth hormone. It is primarily characterized by short stature. Other signs and symptoms vary but may include reduced muscle strength and endurance; hypoglycemia in infancy; delayed puberty; short limbs (arms and legs); and obesity. It is often caused by changes ( mutations ) in the GHR gene and is inherited in an autosomal recessive manner. Treatment is focused on improving growth and generally includes injections of insulin-like growth factor 1 (IGF-1).

OMIM® : 57 Laron syndrome is an autosomal recessive disorder characterized by marked short stature that results from failure to generate insulin-like growth factor I (IGF1; 147440) in response to growth hormone (GH; 139250). GH levels are normal or increased. The disorder is caused by dysfunction of the growth hormone receptor. A Laron syndrome-like phenotype associated with immunodeficiency (245590) is caused by a postreceptor defect, i.e., mutation in the STAT5B gene (604260). Patients with mutations in the GHR gene that cause only partial insensitivity to growth hormone have a form of short stature (604271). (262500) (Updated 05-Apr-2021)

KEGG : 36 Laron syndrome is a rare autosomal recessive disease characterized by insensitivity to growth hormone (GH). The disorder is caused by mutations of the gene encoding the GH receptor (GHR), leading to defective functioning of the GH-IGF1 signalling pathway. The main phenotypic feature is dwarfism, noticeable from birth. Patients have an elevated level of GH and undetectable, or very low IGF1 concentrations in serum.

UniProtKB/Swiss-Prot : 72 Laron syndrome: A severe form of growth hormone insensitivity characterized by growth impairment, short stature, dysfunctional growth hormone receptor, and failure to generate insulin-like growth factor I in response to growth hormone.

Wikipedia : 73 Laron syndrome (LS), also known as growth hormone insensitivity is an autosomal recessive disorder... more...

Sources

Related Diseases for Laron Syndrome

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Diseases related to Laron Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 195)
# Related Disease Score Top Affiliating Genes
1 dwarfism 30.8 GHRHR GHR GH1
2 insulin-like growth factor i 30.2 IGFBP3 IGFBP2 IGFBP1 IGF2 IGF1 GHR
3 acid-labile subunit deficiency 30.2 IGFBP3 IGFALS IGF1
4 glucose intolerance 30.1 IGFBP1 IGF1 GH1 ADIPOQ
5 hypoglycemia 29.9 IGFBP3 IGFBP2 IGFBP1 IGF2 IGF1 GH1
6 silver-russell syndrome 1 29.9 IGFBP3 IGF2 IGF1
7 isolated growth hormone deficiency 29.6 PROP1 IGFBP3 IGF1 GHRHR GHR GH1
8 microvascular complications of diabetes 1 29.6 IGFBP3 IGFBP2 IGFBP1 IGF1
9 hypopituitarism 29.6 PROP1 IGFBP3 IGF1 GHRHR GHR GH1
10 hyperandrogenism 29.5 IGFBP3 IGFBP1 IGF2 IGF1 ADIPOQ
11 vascular disease 29.2 STAT1 IGFBP1 IGF1 ADIPOQ
12 body mass index quantitative trait locus 11 29.0 STAT1 LEPQTL1 IGFBP3 IGFBP2 IGFBP1 IGF1
13 hypothyroidism 28.7 STAT1 PROP1 LEPQTL1 IGFBP3 IGF1 GHR
14 diabetes mellitus 28.7 IGFBP3 IGFBP2 IGFBP1 IGF2 IGF1 GHR
15 hyperinsulinism 28.7 LEPQTL1 IGFBP3 IGFBP1 IGF2 IGF1 GHR
16 type 2 diabetes mellitus 28.6 LEPQTL1 IGFBP3 IGFBP1 IGF2 IGF1 GHR
17 osteoporosis 28.3 STAT1 LEPQTL1 IGFBP3 IGFBP2 IGFBP1 IGF2
18 growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant 11.8
19 growth hormone insensitivity with immunodeficiency 11.5
20 growth hormone insensitivity syndrome with immune dysregulation 1, autosomal recessive 11.4
21 growth hormone insensitivity syndrome with immune dysregulation 1 11.3
22 growth hormone insensitivity syndrome with immune dysregulation 2 11.3
23 growth hormone insensitivity, partial 11.3
24 skin creases, congenital symmetric circumferential, 1 11.0
25 infantile liver failure syndrome 1 11.0
26 rectum cancer 10.4
27 growth hormone deficiency 10.4
28 autosomal recessive disease 10.4
29 slipped capital femoral epiphysis 10.3 IGFBP3 IGF1
30 plica syndrome 10.3
31 synovitis 10.3
32 secondary adrenal insufficiency 10.3 IGFBP3 IGF1
33 non-functioning pituitary adenoma 10.3 GHR GH1
34 pineal hyperplasia, insulin-resistant diabetes mellitus, and somatic abnormalities 10.3 IGFBP3 IGF1
35 genetic obesity 10.2 LEPQTL1 IGF1
36 partial third-nerve palsy 10.2 IGF1 GH1
37 nickel allergic contact dermatitis 10.2 IGF1 GH1
38 precocious puberty 10.2
39 functioning pituitary adenoma 10.2 IGF1 GHR GH1
40 marasmus 10.2 IGFBP3 IGF1 GH1
41 central precocious puberty 10.2 IGFBP3 IGF1 GH1
42 pituitary apoplexy 10.2 IGF1 GH1
43 obesity-hypoventilation syndrome 10.2 LEPQTL1 ADIPOQ
44 pituitary adenoma 1, multiple types 10.2 IGFBP3 IGF1 GH1
45 penis agenesis 10.2
46 skin tag 10.2 IGFBP3 IGF1
47 acanthosis nigricans 10.2 IGF1 GH1 ADIPOQ
48 ovarian cancer 10.2
49 prostate cancer 10.2
50 protein-deficiency anemia 10.2 IGFBP1 GH1

Graphical network of the top 20 diseases related to Laron Syndrome:



Diseases related to Laron Syndrome
Sources

Symptoms & Phenotypes for Laron Syndrome

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Human phenotypes related to Laron Syndrome:

58 31 (show top 50) (show all 51)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 58 31 hallmark (90%) Very frequent (99-80%) HP:0001508
2 delayed skeletal maturation 58 31 frequent (33%) Very frequent (99-80%),Frequent (79-30%) HP:0002750
3 abnormal facial shape 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001999
4 microcephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000252
5 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
6 everted lower lip vermilion 58 31 hallmark (90%) Very frequent (99-80%) HP:0000232
7 microdontia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000691
8 micrognathia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000347
9 delayed eruption of teeth 58 31 frequent (33%) Very frequent (99-80%),Frequent (79-30%) HP:0000684
10 hypercholesterolemia 58 31 hallmark (90%) Occasional (29-5%),Very frequent (99-80%) HP:0003124
11 reduced number of teeth 58 31 hallmark (90%) Very frequent (99-80%) HP:0009804
12 high forehead 58 31 hallmark (90%) Very frequent (99-80%) HP:0000348
13 truncal obesity 58 31 occasional (7.5%) Very frequent (99-80%),Occasional (29-5%) HP:0001956
14 aplasia/hypoplasia involving the nose 58 31 hallmark (90%) Very frequent (99-80%) HP:0009924
15 severe short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0003510
16 insulin resistance 58 31 hallmark (90%) Very frequent (99-80%) HP:0000855
17 hypoplastic nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0005281
18 type ii diabetes mellitus 58 31 frequent (33%) Frequent (79-30%) HP:0005978
19 delayed puberty 58 31 frequent (33%) Frequent (79-30%) HP:0000823
20 hypoglycemia 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0001943
21 short toe 58 31 frequent (33%) Frequent (79-30%) HP:0001831
22 motor delay 58 31 frequent (33%) Frequent (79-30%) HP:0001270
23 brachydactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001156
24 fine hair 58 31 frequent (33%) Frequent (79-30%) HP:0002213
25 hypoplasia of penis 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0008736
26 abnormality of the elbow 58 31 frequent (33%) Frequent (79-30%) HP:0009811
27 underdeveloped supraorbital ridges 58 31 frequent (33%) Frequent (79-30%) HP:0009891
28 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0001249
29 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000365
30 abnormality of the nail 58 31 occasional (7.5%) Occasional (29-5%) HP:0001597
31 immunodeficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0002721
32 hypohidrosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000966
33 diabetes insipidus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000873
34 prematurely aged appearance 58 31 occasional (7.5%) Occasional (29-5%) HP:0007495
35 depressed nasal ridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0000457
36 large fontanelles 58 31 occasional (7.5%) Occasional (29-5%) HP:0000239
37 osteoarthritis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002758
38 high pitched voice 58 31 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0001620
39 blue sclerae 58 31 occasional (7.5%) Occasional (29-5%) HP:0000592
40 hypogonadism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000135
41 diabetes mellitus 58 Frequent (79-30%)
42 abnormality of the skeletal system 58 Frequent (79-30%)
43 abnormal skull morphology 58 Occasional (29-5%)
44 abnormality of the mouth 58 Very frequent (99-80%)
45 abnormality of the endocrine system 58 Very frequent (99-80%)
46 abnormality of metabolism/homeostasis 31 HP:0001939
47 limb undergrowth 31 HP:0009826
48 abnormal joint morphology 31 HP:0001367
49 short long bone 31 HP:0003026
50 small face 31 HP:0000274

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Endocrine Features:
delayed menarche
target resistance to the action of gh

Skeletal:
delayed bone age
markedly advanced osseous maturation for height and age

Skeletal Limbs:
short limbs
limited elbow extensibility
acrohypoplasia

Growth Height:
marked short stature

Skeletal Pelvis:
hip degeneration

Head And Neck Face:
small facies

Voice:
high-pitched voice

Head And Neck Eyes:
blue sclerae (in some patients)

Growth Other:
clinical hyposomatotropism
normal body proportions in childhood
childlike body proportions in adults
greater deviation of stature than head size

Laboratory Abnormalities:
failure to generate somatomedin (or insulinlike growth factor, igf1) in response to growth hormone
normal or increased levels of gh
low igf1 despite normal or increased levels of gh

Clinical features from OMIM®:

262500 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Laron Syndrome according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Reduced mammosphere formation GR00396-S 9.1 GHR IGF1 IGF2 IGFBP3 IL18R1 STAT1

MGI Mouse Phenotypes related to Laron Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.18 ADIPOQ CFI GHR GHRHR IGF1 IGF2
2 immune system MP:0005387 10.11 ADIPOQ CFI GHR GHRHR IGF1 IGF2
3 endocrine/exocrine gland MP:0005379 10.09 ADIPOQ GHR GHRHR IGF1 IGF2 IGFBP3
4 integument MP:0010771 9.92 ADIPOQ GHR GHRHR IGF1 IGF2 IGFBP3
5 limbs/digits/tail MP:0005371 9.8 GHR GHRHR IGF1 IGF2 IGFALS IGFBP3
6 liver/biliary system MP:0005370 9.76 ADIPOQ GHR IGF2 IGFBP1 IGFBP2 IGFBP3
7 renal/urinary system MP:0005367 9.5 ADIPOQ CFI GHR IGF1 IGF2 IGFBP2
8 skeleton MP:0005390 9.23 ADIPOQ GHR GHRHR IGF1 IGF2 IGFALS
Sources

Drugs & Therapeutics for Laron Syndrome

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Drugs for Laron Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Mecasermin Approved, Investigational Phase 2, Phase 3 68562-41-4
2 Hormones Phase 2, Phase 3
3 insulin Phase 2, Phase 3
4 Mitogens Phase 2, Phase 3
5 Insulin, Globin Zinc Phase 2, Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 IGF-I/IGFBP-3 Therapy in Children and Adolescents With Growth Hormone Insenitivity Syndrome (GHIS) Such as Laron Syndrome Completed NCT00368173 Phase 2, Phase 3 rhIGF-I/rhIGFBP-3
2 A Study of the Long-Term Human Recombinant Insulin-Like Growth Factor-1 (rhIGF-1) Treatment in Children With Short Stature Due to Growth Hormone Insensitivity Syndrome (GHIS) Completed NCT00571727 Phase 2, Phase 3 mecasermin
3 Intervention for Reduced Sound Tolerance Completed NCT00890526 Phase 1
4 Preschool Based Obesity Prevention Effectiveness Trial Completed NCT00241878

Search NIH Clinical Center for Laron Syndrome

Cochrane evidence based reviews: laron syndrome

Sources

Genetic Tests for Laron Syndrome

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Genetic tests related to Laron Syndrome:

# Genetic test Affiliating Genes
1 Laron-Type Isolated Somatotropin Defect 29 GHR
Sources

Anatomical Context for Laron Syndrome

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MalaCards organs/tissues related to Laron Syndrome:

40
Pituitary, Bone, Liver, Brain, Heart, Skin, Retina
Sources

Publications for Laron Syndrome

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Articles related to Laron Syndrome:

(show top 50) (show all 420)
# Title Authors PMID Year
1
Diverse growth hormone receptor gene mutations in Laron syndrome. 57 54 61 6
8488849 1993
2
Laron dwarfism and mutations of the growth hormone-receptor gene. 6 57 61
2779634 1989
3
The little women of Loja--growth hormone-receptor deficiency in an inbred population of southern Ecuador. 57 6
2233903 1990
4
Primary growth hormone (GH) insensitivity and insulin-like growth factor deficiency caused by novel compound heterozygous mutations of the GH receptor gene: genetic and functional studies of simple and compound heterozygous states. 61 54 6
17405847 2007
5
An intronic growth hormone receptor mutation causing activation of a pseudoexon is associated with a broad spectrum of growth hormone insensitivity phenotypes. 54 61 6
17148568 2007
6
Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958-2003. 57 54 61
15001582 2004
7
Heterozygous nonsense mutation in exon 3 of the growth hormone receptor (GHR) in severe GH insensitivity (Laron syndrome) and the issue of the origin and function of the GHRd3 isoform. 6 54 61
12679461 2003
8
Four contiguous amino acid substitutions, identified in patients with Laron syndrome, differently affect the binding affinity and intracellular trafficking of the growth hormone receptor. 61 54 6
9851797 1998
9
A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). 61 54 57
9371826 1997
10
Prolonged treatment with recombinant insulin-like growth factor-I in children with growth hormone insensitivity syndrome--a clinical research center study. GHIS Collaborative Group. 57 61 54
8784089 1996
11
A homozygous splice site mutation affecting the intracellular domain of the growth hormone (GH) receptor resulting in Laron syndrome with elevated GH-binding protein. 61 57 54
8626815 1996
12
Facial morphometry of Ecuadorian patients with growth hormone receptor deficiency/Laron syndrome. 61 54 57
7815422 1994
13
Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism. 54 61 6
8450064 1993
14
Mutation creating a new splice site in the growth hormone receptor genes of 37 Ecuadorean patients with Laron syndrome. 6 54 61
1284474 1992
15
Effects of the infusion of insulin-like growth factor I in a child with growth hormone insensitivity syndrome (Laron dwarfism). 54 61 57
2023608 1991
16
Are adult patients with Laron syndrome osteopenic? A comparison between dual-energy X-ray absorptiometry and volumetric bone densities. 61 57
14557426 2003
17
Therapy for 6.5-7.5 years with recombinant insulin-like growth factor I in children with growth hormone insensitivity syndrome: a clinical research center study. 54 57
11297575 2001
18
Recombinant human insulin-like growth factor I has significant anabolic effects in adults with growth hormone receptor deficiency: studies on protein, glucose, and lipid metabolism. 54 57
10999782 2000
19
Growth hormone receptor deficiency in Ecuador. 54 57
10599699 1999
20
Normal intelligence with severe insulin-like growth factor I deficiency due to growth hormone receptor deficiency: a controlled study in a genetically homogeneous population. 6 54
9626125 1998
21
Clinical, biochemical, and molecular investigations of a genetic isolate of growth hormone insensitivity (Laron's syndrome). 57 54
9024234 1997
22
Defective membrane expression of human growth hormone (GH) receptor causes Laron-type GH insensitivity syndrome. 61 6
1719554 1991
23
Recurrent nonsense mutations in the growth hormone receptor from patients with Laron dwarfism. 6 61
1999489 1991
24
Correction and withdrawal of conclusion--a child with phenotypic Laron dwarfism and normal somatomedin levels. 57 61
2288600 1990
25
A child with phenotypic Laron dwarfism and normal somatomedin levels. 57 61
2725626 1989
26
A child with phenotypic Laron dwarfism and normal somatomedin levels. 61 57
2913494 1989
27
Absence of serum growth hormone binding protein in patients with growth hormone receptor deficiency (Laron dwarfism). 57 61
3474620 1987
28
Tissues of the Laron dwarf are sensitive to insulin-like growth factor I but not to growth hormone. 57 61
3031118 1987
29
Peripheral unresponsiveness to human growth hormone in Laron dwarfism. 61 57
6106895 1980
30
Receptor-active growth hormone in Laron dwarfism. 61 57
177445 1976
31
Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. 57
21325617 2011
32
A novel C-terminal growth hormone receptor (GHR) mutation results in impaired GHR-STAT5 but normal STAT-3 signaling. 6
15536163 2005
33
Growth hormone (GH) insensitivity syndrome due to a GH receptor truncated after Box1, resulting in isolated failure of STAT 5 signal transduction. 6
15001620 2004
34
Leptin concentrations in GH deficiency: the effect of GH insensitivity. 6
11836282 2002
35
Pseudoexon activation as a novel mechanism for disease resulting in atypical growth-hormone insensitivity. 6
11468686 2001
36
Stature in Ecuadorians heterozygous for growth hormone receptor gene E180 splice mutation does not differ from that of homozygous normal relatives. 6
9661611 1998
37
Phenotype: genotype relationships in growth hormone insensitivity syndrome. 57
9360502 1997
38
Aspartate 171 is the major primate-specific determinant of human growth hormone. Engineering porcine growth hormone to activate the human receptor. 57
9341147 1997
39
A dominant-negative mutation of the growth hormone receptor causes familial short stature. 57
9140387 1997
40
Two-year treatment of growth hormone (GH) receptor deficiency with recombinant insulin-like growth factor I in 22 children: comparison of two dosage levels and to GH-treated GH deficiency. 57
9024266 1997
41
Mutations of the growth hormone receptor in children with idiopathic short stature. The Growth Hormone Insensitivity Study Group. 57
7565946 1995
42
A single arginine residue determines species specificity of the human growth hormone receptor. 57
7862673 1995
43
Growth response of children with non-growth-hormone deficiency and marked short stature during three years of growth hormone therapy. 57
8345416 1993
44
Molecular biology of growth hormone receptor dysfunction. 57
1458007 1992
45
Effects of insulin-like growth factor on linear growth, head circumference, and body fat in patients with Laron-type dwarfism. 57
1349669 1992
46
Laron-type dwarfism with apparently normal high affinity serum growth hormone-binding protein. 57
1934534 1991
47
Growth hormone receptor (Ghr) and hemoglobin alpha-chain pseudogene 3 (Hba-ps3) map proximal to the myelocytomatosis oncogene (Myc) on mouse chromosome 15. 57
1794046 1991
48
High-affinity serum growth-hormone-binding protein, absent in Laron-type dwarfism, is diminished in heterozygous parents. 57
2074091 1990
49
The receptors for prolactin and growth hormone are localized in the same region of human chromosome 5. 57
2369845 1990
50
Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism. 6
2813379 1989
Sources

Variations for Laron Syndrome

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ClinVar genetic disease variations for Laron Syndrome:

6 (show top 50) (show all 123)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GHR GHR, EX4,6DEL Deletion Pathogenic 8631 GRCh37:
GRCh38:
2 GHR NM_000163.5(GHR):c.341T>C (p.Phe114Ser) SNV Pathogenic 8632 rs121909357 GRCh37: 5:42695093-42695093
GRCh38: 5:42694991-42694991
3 GHR NM_000163.5(GHR):c.181C>T (p.Arg61Ter) SNV Pathogenic 8633 rs121909358 GRCh37: 5:42689036-42689036
GRCh38: 5:42688934-42688934
4 GHR NM_000163.5(GHR):c.168C>A (p.Cys56Ter) SNV Pathogenic 8634 rs121909359 GRCh37: 5:42689023-42689023
GRCh38: 5:42688921-42688921
5 GHR NM_000163.5(GHR):c.594A>G (p.Glu198=) SNV Pathogenic 8635 rs121909360 GRCh37: 5:42700080-42700080
GRCh38: 5:42699978-42699978
6 GHR NM_000163.5(GHR):c.703C>T (p.Arg235Ter) SNV Pathogenic 8639 rs121909363 GRCh37: 5:42711393-42711393
GRCh38: 5:42711291-42711291
7 GHR GHR, IVS4DS, G-A, +1 SNV Pathogenic 8640 GRCh37:
GRCh38:
8 GHR GHR, 2-BP DEL, FS51TER Deletion Pathogenic 8641 GRCh37:
GRCh38:
9 GHR NM_000163.5(GHR):c.619-1G>T SNV Pathogenic 8642 rs730880281 GRCh37: 5:42711308-42711308
GRCh38: 5:42711206-42711206
10 GHR GHR, 2-BP DEL, FS234TER Deletion Pathogenic 8643 GRCh37:
GRCh38:
11 GHR NM_000163.5(GHR):c.515A>C (p.Gln172Pro) SNV Pathogenic 8645 rs121909368 GRCh37: 5:42700001-42700001
GRCh38: 5:42699899-42699899
12 GHR NM_000163.5(GHR):c.518T>G (p.Val173Gly) SNV Pathogenic 8648 rs121909369 GRCh37: 5:42700004-42700004
GRCh38: 5:42699902-42699902
13 GHR NM_000163.5(GHR):c.508G>C (p.Asp170His) SNV Pathogenic 8653 rs121909366 GRCh37: 5:42699994-42699994
GRCh38: 5:42699892-42699892
14 GHR NM_000163.5(GHR):c.512T>C (p.Ile171Thr) SNV Pathogenic 8654 rs121909367 GRCh37: 5:42699998-42699998
GRCh38: 5:42699896-42699896
15 GHR GHR, IVS6AS, A-G, -1 SNV Pathogenic 8655 GRCh37:
GRCh38:
16 GHR GHR, 22-BP DEL Deletion Pathogenic 8656 GRCh37:
GRCh38:
17 GHR NM_000163.5(GHR):c.102G>A (p.Trp34Ter) SNV Pathogenic 8657 rs121909370 GRCh37: 5:42629171-42629171
GRCh38: 5:42629069-42629069
18 GHR NM_000163.5(GHR):c.303C>A (p.Cys101Ter) SNV Pathogenic 8659 rs121909371 GRCh37: 5:42695055-42695055
GRCh38: 5:42694953-42694953
19 GHR GHR, 1-BP DEL, 1776G Deletion Pathogenic 8660 GRCh37:
GRCh38:
20 GHR NM_000163.5(GHR):c.335G>C (p.Cys112Ser) SNV Pathogenic 8662 rs121909372 GRCh37: 5:42695087-42695087
GRCh38: 5:42694985-42694985
21 GHR NM_000163.5(GHR):c.504T>G (p.His168Gln) SNV Pathogenic 8663 rs121909373 GRCh37: 5:42699990-42699990
GRCh38: 5:42699888-42699888
22 GHR NM_000163.5(GHR):c.281G>A (p.Trp94Ter) SNV Pathogenic 397577 rs1060499692 GRCh37: 5:42695033-42695033
GRCh38: 5:42694931-42694931
23 GHR NM_000163.5(GHR):c.364T>C (p.Trp122Arg) SNV Pathogenic 492773 rs190314158 GRCh37: 5:42695116-42695116
GRCh38: 5:42695014-42695014
24 GHR NM_000163.5(GHR):c.945G>A (p.Lys315=) SNV Pathogenic 492774 rs1554040858 GRCh37: 5:42718223-42718223
GRCh38: 5:42718121-42718121
25 GHR NM_000163.5(GHR):c.267-2A>G SNV Pathogenic 869191 GRCh37: 5:42695017-42695017
GRCh38: 5:42694915-42694915
26 GHR NM_000163.5(GHR):c.344A>C (p.Asn115Thr) SNV Likely pathogenic 807419 rs1579626395 GRCh37: 5:42695096-42695096
GRCh38: 5:42694994-42694994
27 GHR NM_000163.5(GHR):c.484G>A (p.Val162Ile) SNV Conflicting interpretations of pathogenicity 8652 rs6413484 GRCh37: 5:42699970-42699970
GRCh38: 5:42699868-42699868
28 GHR NM_000163.5(GHR):c.12G>C (p.Trp4Cys) SNV Uncertain significance 492772 rs1554020272 GRCh37: 5:42565988-42565988
GRCh38: 5:42565886-42565886
29 LOC107963950 , GHR NM_000163.5(GHR):c.-118C>T SNV Uncertain significance 904296 GRCh37: 5:42423951-42423951
GRCh38: 5:42423849-42423849
30 LOC107963950 , GHR NM_000163.5(GHR):c.-89G>T SNV Uncertain significance 904297 GRCh37: 5:42423980-42423980
GRCh38: 5:42423878-42423878
31 LOC107963950 , GHR NM_000163.5(GHR):c.-76C>T SNV Uncertain significance 904298 GRCh37: 5:42423993-42423993
GRCh38: 5:42423891-42423891
32 LOC107963950 , GHR NM_000163.5(GHR):c.-74C>T SNV Uncertain significance 904299 GRCh37: 5:42423995-42423995
GRCh38: 5:42423893-42423893
33 GHR NM_000163.5(GHR):c.*1847T>G SNV Uncertain significance 353712 rs886060648 GRCh37: 5:42721373-42721373
GRCh38: 5:42721271-42721271
34 GHR NM_000163.5(GHR):c.876-15T>G SNV Uncertain significance 353683 rs199960137 GRCh37: 5:42718139-42718139
GRCh38: 5:42718037-42718037
35 GHR NM_000163.5(GHR):c.*1916T>G SNV Uncertain significance 353714 rs886060650 GRCh37: 5:42721442-42721442
GRCh38: 5:42721340-42721340
36 GHR NM_000163.5(GHR):c.875+10G>C SNV Uncertain significance 353682 rs35111599 GRCh37: 5:42713631-42713631
GRCh38: 5:42713529-42713529
37 GHR NM_000163.5(GHR):c.*941A>G SNV Uncertain significance 353703 rs886060644 GRCh37: 5:42720467-42720467
GRCh38: 5:42720365-42720365
38 GHR NM_000163.5(GHR):c.*2042A>G SNV Uncertain significance 353717 rs886060652 GRCh37: 5:42721568-42721568
GRCh38: 5:42721466-42721466
39 GHR NM_000163.5(GHR):c.*670T>C SNV Uncertain significance 353697 rs566673833 GRCh37: 5:42720196-42720196
GRCh38: 5:42720094-42720094
40 GHR NM_000163.5(GHR):c.*1689A>T SNV Uncertain significance 353709 rs886060647 GRCh37: 5:42721215-42721215
GRCh38: 5:42721113-42721113
41 GHR NM_000163.5(GHR):c.1832C>T (p.Ala611Val) SNV Uncertain significance 353689 rs775194712 GRCh37: 5:42719441-42719441
GRCh38: 5:42719339-42719339
42 GHR NM_000163.5(GHR):c.1699A>T (p.Ile567Phe) SNV Uncertain significance 353687 rs373401634 GRCh37: 5:42719308-42719308
GRCh38: 5:42719206-42719206
43 GHR NM_000163.5(GHR):c.*154G>A SNV Uncertain significance 353692 rs565340420 GRCh37: 5:42719680-42719680
GRCh38: 5:42719578-42719578
44 GHR NM_000163.5(GHR):c.660G>T (p.Leu220Phe) SNV Uncertain significance 353681 rs200851410 GRCh37: 5:42711350-42711350
GRCh38: 5:42711248-42711248
45 GHR NM_000163.5(GHR):c.*1539G>A SNV Uncertain significance 353707 rs181187685 GRCh37: 5:42721065-42721065
GRCh38: 5:42720963-42720963
46 GHR NM_000163.5(GHR):c.1899G>A (p.Leu633=) SNV Uncertain significance 353690 rs758515730 GRCh37: 5:42719508-42719508
GRCh38: 5:42719406-42719406
47 GHR NM_000163.5(GHR):c.-10T>C SNV Uncertain significance 353677 rs201804261 GRCh37: 5:42565967-42565967
GRCh38: 5:42565865-42565865
48 GHR NM_000163.5(GHR):c.*1892T>A SNV Uncertain significance 353713 rs886060649 GRCh37: 5:42721418-42721418
GRCh38: 5:42721316-42721316
49 GHR NM_000163.5(GHR):c.1025G>T (p.Trp342Leu) SNV Uncertain significance 353684 rs886060641 GRCh37: 5:42718634-42718634
GRCh38: 5:42718532-42718532
50 GHR NM_000163.5(GHR):c.*2292A>G SNV Uncertain significance 353719 rs35415717 GRCh37: 5:42721818-42721818
GRCh38: 5:42721716-42721716

UniProtKB/Swiss-Prot genetic disease variations for Laron Syndrome:

72 (show all 17)
# Symbol AA change Variation ID SNP ID
1 GHR p.Arg89Lys VAR_002709
2 GHR p.Phe114Ser VAR_002710 rs121909357
3 GHR p.Val143Ala VAR_002711
4 GHR p.Val162Asp VAR_002712
5 GHR p.Asp170His VAR_002713 rs121909366
6 GHR p.Arg179Cys VAR_002714 rs121909362
7 GHR p.Arg229Gly VAR_002715
8 GHR p.Cys56Ser VAR_018426
9 GHR p.Ser58Leu VAR_018427
10 GHR p.Trp68Arg VAR_018428
11 GHR p.Pro149Gln VAR_018429 rs121909365
12 GHR p.Ile171Thr VAR_018431 rs121909367
13 GHR p.Gln172Pro VAR_018432 rs121909368
14 GHR p.Val173Gly VAR_018433 rs121909369
15 GHR p.Tyr226Cys VAR_018434
16 GHR p.Ser244Ile VAR_018435 rs116439644
17 GHR p.Asp262Asn VAR_018436

Sources

Expression for Laron Syndrome

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Search GEO for disease gene expression data for Laron Syndrome.
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Pathways for Laron Syndrome

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Pathways related to Laron Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 Neuroactive ligand-receptor interaction hsa04080
2 Cytokine-cytokine receptor interaction hsa04060
3 JAK-STAT signaling pathway hsa04630
4 PI3K-Akt signaling pathway hsa04151

Pathways related to Laron Syndrome according to GeneCards Suite gene sharing:

(show all 17)
# Super pathways Score Top Affiliating Genes
1
TGF-Beta Pathway 63
Show member pathways
 13.33 STAT5B STAT1 IL18R1 IGF2 IGF1 GHR
2
IL-2 Pathway 63
Show member pathways
 12.99 STAT5B STAT1 IGF2 IGF1 GHR GH1
3
PI3K-Akt signaling pathway 36
Show member pathways
 12.77 STAT1 IGF2 IGF1 GHR GH1
4
Regulation of lipid metabolism Insulin signaling-generic cascades 23
Show member pathways
 12.65 STAT1 IGFBP3 IGF1 GHR GH1
5
Relaxin signaling pathway 36
Show member pathways
 12.35 STAT5B STAT1 IGFBP3 IGFALS IGF1 GHRHR
6
Glucose / Energy Metabolism 4
12.3 IGFBP3 IGFBP2 IGFBP1 ADIPOQ
7
Development IGF-1 receptor signaling 23
Show member pathways
 12.18 STAT5B STAT1 IGFBP3 IGFBP2 IGFBP1 IGF2
8
JAK-STAT signaling pathway 36
Show member pathways
 12.16 STAT5B STAT1 GHR GH1
9
Immune response IFN alpha/beta signaling pathway 23
Show member pathways
 12.07 STAT1 IGF2 IGF1 GH1
10
Adipogenesis 1
11.89 STAT5B STAT1 IGF1 GH1 ADIPOQ
11
Mesenchymal Stem Cell Differentiation Pathways and Lineage-specific Markers 64
11.65 IGFBP3 IGF1 ADIPOQ
12
Th1 Differentiation Pathway 64
Show member pathways
 11.49 STAT5B STAT1 IL18R1
13
Endochondral Ossification 1
11.25 STAT5B STAT1 IGF2 IGF1 GHR GH1
14
Growth hormone receptor signaling 65
Show member pathways
 11.24 STAT5B STAT1 GHR GH1
15
Photodynamic therapy-induced HIF-1 survival signaling 1
11.15 IGFBP3 IGFBP2 IGFBP1
16
Immune response_Oncostatin M signaling via JAK-Stat in human cells 23
10.85 STAT5B STAT1
17
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) 65
10.42 IGFBP3 IGFBP2 IGFBP1 IGFALS IGF2 IGF1
Sources

GO Terms for Laron Syndrome

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Cellular components related to Laron Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.85 IGFBP3 IGFBP2 IGFBP1 IGFALS IGF2 IGF1
2 extracellular space GO:0005615 9.65 IGFBP3 IGFBP2 IGFBP1 IGFALS IGF2 IGF1
3 insulin-like growth factor binding protein complex GO:0016942 9.32 IGFBP3 IGF1
4 growth hormone receptor complex GO:0070195 9.26 GHR GH1
5 insulin-like growth factor ternary complex GO:0042567 8.8 IGFBP3 IGFALS IGF1

Biological processes related to Laron Syndrome according to GeneCards Suite gene sharing:

(show all 27)
# Name GO ID Score Top Affiliating Genes
1 signal transduction GO:0007165 10.1 STAT5B STAT1 IL18R1 IGFBP2 IGFBP1 IGFALS
2 positive regulation of cell proliferation GO:0008284 9.99 STAT5B STAT1 IGF2 IGF1 GHRHR
3 cellular protein metabolic process GO:0044267 9.85 IGFBP3 IGFBP2 IGFBP1 IGFALS IGF2 IGF1
4 response to estradiol GO:0032355 9.81 STAT5B IGFBP2 GHR GH1
5 positive regulation of MAPK cascade GO:0043410 9.8 IGFBP3 IGF2 IGF1
6 cellular response to insulin stimulus GO:0032869 9.78 STAT1 GHRHR GHR ADIPOQ
7 response to nutrient GO:0007584 9.77 STAT1 IGFBP2 ADIPOQ
8 positive regulation of tyrosine phosphorylation of STAT protein GO:0042531 9.75 IGF1 GHR GH1
9 response to peptide hormone GO:0043434 9.74 STAT5B STAT1 GHR
10 response to glucocorticoid GO:0051384 9.73 IGFBP2 GHRHR GHR ADIPOQ
11 positive regulation of peptidyl-tyrosine phosphorylation GO:0050731 9.72 IGF2 IGF1 GHR GH1 ADIPOQ
12 JAK-STAT cascade GO:0007259 9.71 STAT5B STAT1 GHR
13 cellular response to hormone stimulus GO:0032870 9.7 STAT5B IGFBP2 GHR
14 regulation of multicellular organism growth GO:0040014 9.67 STAT5B IGF1 GHR
15 regulation of glucose metabolic process GO:0010906 9.63 IGFBP3 ADIPOQ
16 JAK-STAT cascade involved in growth hormone signaling pathway GO:0060397 9.63 STAT5B GHR GH1
17 positive regulation of glycogen biosynthetic process GO:0045725 9.62 IGF2 IGF1
18 insulin-like growth factor receptor signaling pathway GO:0048009 9.62 IGF1 GHR
19 growth hormone receptor signaling pathway GO:0060396 9.61 GHR GH1
20 hormone metabolic process GO:0042445 9.61 GHRHR GHR
21 interleukin-9-mediated signaling pathway GO:0038113 9.58 STAT5B STAT1
22 positive regulation of glycogen (starch) synthase activity GO:2000467 9.56 IGF2 ADIPOQ
23 positive regulation of activated T cell proliferation GO:0042104 9.56 STAT5B IGFBP2 IGF2 IGF1
24 taurine metabolic process GO:0019530 9.55 STAT5B GHR
25 positive regulation of insulin-like growth factor receptor signaling pathway GO:0043568 9.46 IGFBP3 IGF1 GHRHR GH1
26 regulation of insulin-like growth factor receptor signaling pathway GO:0043567 9.26 IGFBP3 IGFBP2 IGFBP1 GHRHR
27 positive regulation of multicellular organism growth GO:0040018 9.02 STAT5B IGF2 GHRHR GHR GH1

Molecular functions related to Laron Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hormone activity GO:0005179 9.62 IGF2 IGF1 GH1 ADIPOQ
2 insulin-like growth factor I binding GO:0031994 9.43 IGFBP3 IGFBP2 IGFBP1
3 insulin receptor binding GO:0005158 9.4 IGF2 IGF1
4 insulin-like growth factor receptor binding GO:0005159 9.37 IGF2 IGF1
5 insulin-like growth factor II binding GO:0031995 9.33 IGFBP3 IGFBP2 IGFBP1
6 insulin-like growth factor binding GO:0005520 9.26 IGFBP3 IGFBP2 IGFBP1 IGFALS
7 growth factor binding GO:0019838 9.02 IGFBP3 IGFBP2 IGFBP1 GHRHR GHR
Sources

Sources for Laron Syndrome

About this section
3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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