Drug Information
Drug (ID: DG01442) and It's Reported Resistant Information
Name |
Thyrotropin
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Indication |
In total 1 Indication(s)
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Drug Resistance Disease(s) |
Disease(s) with Clinically Reported Resistance for This Drug
(2 diseases)
Albright hereditary osteodystrophy syndrome [ICD-11: LD44]
[1]
Hypothyroidism [ICD-11: 5A00]
[1]
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Target | Thyrotropin receptor (TSHR) | TSHR_HUMAN | [1] | ||
Click to Show/Hide the Molecular Information and External Link(s) of This Drug | |||||
TTD Drug ID |
Type(s) of Resistant Mechanism of This Drug
UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-05: Endocrine/nutritional/metabolic diseases
Hypothyroidism [ICD-11: 5A00]
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Key Molecule: NK2 homeobox 1 (NKX2-1) | [1] | |||
Molecule Alteration | Missense mutation | p.G2626T |
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Resistant Disease | Subclinical hypothyroidism [ICD-11: 5A00.22] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Haploinsufficiency for NKX2-1, due to either chromosomal deletions encompassing the gene locus [94] or deleterious gene mutations, produces a "brain-thyroid-lung" syndrome. The severity of the individual components of the syndrome is very variable, and includes: 1) RTSH (70% of patients), 2) "benign hereditary chorea" (90% of patients) manifesting as neonatal hypotonia preceding the development of juvenile choreoathetosis and ataxia, 3) respiratory distress (55% of patients) due to lung hypoplasia causing significantly increased mortality. | |||
Key Molecule: NK2 homeobox 1 (NKX2-1) | [1] | |||
Molecule Alteration | Missense mutation | p.C2519A |
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Resistant Disease | Subclinical hypothyroidism [ICD-11: 5A00.22] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Haploinsufficiency for NKX2-1, due to either chromosomal deletions encompassing the gene locus [94] or deleterious gene mutations, produces a "brain-thyroid-lung" syndrome. The severity of the individual components of the syndrome is very variable, and includes: 1) RTSH (70% of patients), 2) "benign hereditary chorea" (90% of patients) manifesting as neonatal hypotonia preceding the development of juvenile choreoathetosis and ataxia, 3) respiratory distress (55% of patients) due to lung hypoplasia causing significantly increased mortality. | |||
Key Molecule: NK2 homeobox 1 (NKX2-1) | [1] | |||
Molecule Alteration | Missense mutation | p.C1302A |
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Resistant Disease | Subclinical hypothyroidism [ICD-11: 5A00.22] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Haploinsufficiency for NKX2-1, due to either chromosomal deletions encompassing the gene locus [94] or deleterious gene mutations, produces a "brain-thyroid-lung" syndrome. The severity of the individual components of the syndrome is very variable, and includes: 1) RTSH (70% of patients), 2) "benign hereditary chorea" (90% of patients) manifesting as neonatal hypotonia preceding the development of juvenile choreoathetosis and ataxia, 3) respiratory distress (55% of patients) due to lung hypoplasia causing significantly increased mortality. | |||
Key Molecule: NK2 homeobox 1 (NKX2-1) | [1] | |||
Molecule Alteration | Missense mutation | p.G2626T |
||
Resistant Disease | Congenital hypothyroidism [ICD-11: 5A00.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Haploinsufficiency for NKX2-1, due to either chromosomal deletions encompassing the gene locus [94] or deleterious gene mutations, produces a "brain-thyroid-lung" syndrome. The severity of the individual components of the syndrome is very variable, and includes: 1) RTSH (70% of patients), 2) "benign hereditary chorea" (90% of patients) manifesting as neonatal hypotonia preceding the development of juvenile choreoathetosis and ataxia, 3) respiratory distress (55% of patients) due to lung hypoplasia causing significantly increased mortality. | |||
Key Molecule: NK2 homeobox 1 (NKX2-1) | [1] | |||
Molecule Alteration | Missense mutation | p.C2519A |
||
Resistant Disease | Congenital hypothyroidism [ICD-11: 5A00.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Haploinsufficiency for NKX2-1, due to either chromosomal deletions encompassing the gene locus [94] or deleterious gene mutations, produces a "brain-thyroid-lung" syndrome. The severity of the individual components of the syndrome is very variable, and includes: 1) RTSH (70% of patients), 2) "benign hereditary chorea" (90% of patients) manifesting as neonatal hypotonia preceding the development of juvenile choreoathetosis and ataxia, 3) respiratory distress (55% of patients) due to lung hypoplasia causing significantly increased mortality. | |||
Key Molecule: NK2 homeobox 1 (NKX2-1) | [1] | |||
Molecule Alteration | Missense mutation | p.C1302A |
||
Resistant Disease | Congenital hypothyroidism [ICD-11: 5A00.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Haploinsufficiency for NKX2-1, due to either chromosomal deletions encompassing the gene locus [94] or deleterious gene mutations, produces a "brain-thyroid-lung" syndrome. The severity of the individual components of the syndrome is very variable, and includes: 1) RTSH (70% of patients), 2) "benign hereditary chorea" (90% of patients) manifesting as neonatal hypotonia preceding the development of juvenile choreoathetosis and ataxia, 3) respiratory distress (55% of patients) due to lung hypoplasia causing significantly increased mortality. | |||
Key Molecule: Paired box 8 (PAX8) | [1] | |||
Molecule Alteration | Missense mutation | p.L16P |
||
Resistant Disease | Subclinical hypothyroidism [ICD-11: 5A00.22] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | PAX8 mutations are not a relevant cause of sporadic thyroid ectopy or genuine agenesis but found in a minority of cases (e.g. 1/28 German, 1/16 Chinese) within the normotopic hypoplasia subgroup. More generally, heterozygous PAX8 LOF mutations have to be considered as another cause of RTSH that is clinically and by thyroid function tests indistinguishable from that caused by TSHR mutations. The clinical severity can thus range from subclinical hypothyroidism with normal-sized gland to overt hypothyroidism with severe thyroid gland hypoplasia. | |||
Key Molecule: Paired box 8 (PAX8) | [1] | |||
Molecule Alteration | Missense mutation | p.F20S |
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Resistant Disease | Subclinical hypothyroidism [ICD-11: 5A00.22] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | PAX8 mutations are not a relevant cause of sporadic thyroid ectopy or genuine agenesis but found in a minority of cases (e.g. 1/28 German, 1/16 Chinese) within the normotopic hypoplasia subgroup. More generally, heterozygous PAX8 LOF mutations have to be considered as another cause of RTSH that is clinically and by thyroid function tests indistinguishable from that caused by TSHR mutations. The clinical severity can thus range from subclinical hypothyroidism with normal-sized gland to overt hypothyroidism with severe thyroid gland hypoplasia. | |||
Key Molecule: Paired box 8 (PAX8) | [1] | |||
Molecule Alteration | Missense mutation | p.R133Q |
||
Resistant Disease | Subclinical hypothyroidism [ICD-11: 5A00.22] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | PAX8 mutations are not a relevant cause of sporadic thyroid ectopy or genuine agenesis but found in a minority of cases (e.g. 1/28 German, 1/16 Chinese) within the normotopic hypoplasia subgroup. More generally, heterozygous PAX8 LOF mutations have to be considered as another cause of RTSH that is clinically and by thyroid function tests indistinguishable from that caused by TSHR mutations. The clinical severity can thus range from subclinical hypothyroidism with normal-sized gland to overt hypothyroidism with severe thyroid gland hypoplasia. | |||
Key Molecule: Paired box 8 (PAX8) | [1] | |||
Molecule Alteration | Missense mutation | p.L16P |
||
Resistant Disease | Congenital hypothyroidism [ICD-11: 5A00.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | PAX8 mutations are not a relevant cause of sporadic thyroid ectopy or genuine agenesis but found in a minority of cases (e.g. 1/28 German, 1/16 Chinese) within the normotopic hypoplasia subgroup. More generally, heterozygous PAX8 LOF mutations have to be considered as another cause of RTSH that is clinically and by thyroid function tests indistinguishable from that caused by TSHR mutations. The clinical severity can thus range from subclinical hypothyroidism with normal-sized gland to overt hypothyroidism with severe thyroid gland hypoplasia. | |||
Key Molecule: Paired box 8 (PAX8) | [1] | |||
Molecule Alteration | Missense mutation | p.F20S |
||
Resistant Disease | Congenital hypothyroidism [ICD-11: 5A00.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | PAX8 mutations are not a relevant cause of sporadic thyroid ectopy or genuine agenesis but found in a minority of cases (e.g. 1/28 German, 1/16 Chinese) within the normotopic hypoplasia subgroup. More generally, heterozygous PAX8 LOF mutations have to be considered as another cause of RTSH that is clinically and by thyroid function tests indistinguishable from that caused by TSHR mutations. The clinical severity can thus range from subclinical hypothyroidism with normal-sized gland to overt hypothyroidism with severe thyroid gland hypoplasia. | |||
Key Molecule: Paired box 8 (PAX8) | [1] | |||
Molecule Alteration | Missense mutation | p.R133Q |
||
Resistant Disease | Congenital hypothyroidism [ICD-11: 5A00.0] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | PAX8 mutations are not a relevant cause of sporadic thyroid ectopy or genuine agenesis but found in a minority of cases (e.g. 1/28 German, 1/16 Chinese) within the normotopic hypoplasia subgroup. More generally, heterozygous PAX8 LOF mutations have to be considered as another cause of RTSH that is clinically and by thyroid function tests indistinguishable from that caused by TSHR mutations. The clinical severity can thus range from subclinical hypothyroidism with normal-sized gland to overt hypothyroidism with severe thyroid gland hypoplasia. |
ICD-20: Developmental anomalies
Albright hereditary osteodystrophy syndrome [ICD-11: LD44]
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Key Molecule: Adenylate cyclase-stimulating G alpha protein (GNAS) | [1] | |||
Molecule Alteration | Expression | Down-regulation |
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Resistant Disease | Albright hereditary osteodystrophy syndrome [ICD-11: LD44.20] | |||
Experimental Note | Identified from the Human Clinical Data | |||
Mechanism Description | Heterozygous germline mutations in the gene encoding the alpha subunit of G stimulatory protein (Gsalpha, GNAS1) cause hypocalcemia and hyperphosphatemia due to impaired signaling transduction from the parathormone receptor (pseudohypoparathyroidism, PHP Ia). Haploinsufficiency for GNAS1 also explains the resistance to other hormones, specifically gonadotropins and TSH. |
References
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