Hypothyroidism, Congenital, Nongoitrous, 1 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

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Aliases & Classifications for Hypothyroidism, Congenital, Nongoitrous, 1

MalaCards integrated aliases for Hypothyroidism, Congenital, Nongoitrous, 1:

Name: Hypothyroidism, Congenital, Nongoitrous, 1 ⁵⁷ ²⁹ ⁶ ⁷³

Tsh Resistance ⁵⁷ ⁷⁵ ⁵⁵

Hypothyroidism Due to Unresponsiveness to Thyrotropin ⁵⁷ ⁷⁵

Thyrotropin Resistance ⁵⁷ ⁷⁵

Chng1 ⁵⁷ ⁷⁵

Rtsh ⁵⁷ ⁷⁵

Hypothyroidism, Congenital, Due to Tsh Resistance ⁵⁷

Congenital Hypothyroidism Due to Tsh Resistance ⁷⁵

Hypothyroidism Due to Tsh Receptor Mutations ⁵⁹

Hypothyroidism, Congenital, Non-Goitrous, 1 ⁷⁵

Thyroid-Stimulating Hormone, Resistance to ⁵⁷

Hypothyroidism, Congenital, Nongoitrous, 3 ⁷³

Thyroid-Stimulating Hormone Resistance ⁷⁵

Thyroid Hormone Resistance Syndrome ⁷³

Thyroid-Stimulating Hormone ; Rtsh ⁵⁷

Hypothyroidism, Nonautoimmune ⁵⁷

Non-Autoimmune Hypothyroidism ⁷⁵

Characteristics:

Orphanet epidemiological data:

⁵⁹

hypothyroidism due to tsh receptor mutations
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

⁵⁷

Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
most patients are asymptomatic and are detected by newborn screening
variable severity ranging from asymptomatic euthyroid to severe hypothyroidism

HPO:

³²

hypothyroidism, congenital, nongoitrous, 1:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Endocrine diseases

See all MalaCards categories (disease lists)

ICD10: ³⁴ ³³

Endocrine, nutritional and metabolic diseases

Disorders of thyroid gland

Other hypothyroidism

Congenital hypothyroidism without goitre

Hypothyroidism due to medicaments and other exogenous substances

Hypothyroidism, unspecified

Other specified hypothyroidism

Orphanet: ⁵⁹

Rare endocrine diseases

External Ids:

OMIM ⁵⁷ 275200

Orphanet ⁵⁹ ORPHA90673

ICD10 via Orphanet ³⁴ E03.1

MedGen ⁴² C3493776 C2940786 CN074268

MeSH ⁴⁴ D003409

ICD10 ³³ E03.2 E03.8 E03.9

UMLS ⁷³ C3493776 C2940785

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Summaries for Hypothyroidism, Congenital, Nongoitrous, 1

UniProtKB/Swiss-Prot : ⁷⁵ Hypothyroidism, congenital, non-goitrous, 1: A non-autoimmune condition characterized by resistance to thyroid- stimulating hormone (TSH) leading to increased levels of plasma TSH and low levels of thyroid hormone. It presents variable severity depending on the completeness of the defect. Most patients are euthyroid and asymptomatic, with a normal sized thyroid gland. Only a subset of patients develop hypothyroidism and present a hypoplastic thyroid gland.

MalaCards based summary : Hypothyroidism, Congenital, Nongoitrous, 1, also known as tsh resistance, is related to hyperthyroidism, nonautoimmune and hypothyroidism. An important gene associated with Hypothyroidism, Congenital, Nongoitrous, 1 is TSHR (Thyroid Stimulating Hormone Receptor), and among its related pathways/superpathways are cAMP signaling pathway and G alpha (s) signalling events. Affiliated tissues include thyroid and skin, and related phenotypes are hypothyroidism and muscular hypotonia

OMIM : ⁵⁷ Resistance to thyroid-stimulating hormone (TSH; see 188540), a hallmark of congenital nongoitrous hypothyroidism, causes increased levels of plasma TSH and low levels of thyroid hormone. Only a subset of patients develop frank hypothyroidism; the remainder are euthyroid and asymptomatic (so-called compensated hypothyroidism) and are usually detected by neonatal screening programs (Paschke and Ludgate, 1997). (275200)

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Related Diseases for Hypothyroidism, Congenital, Nongoitrous, 1

Diseases in the Hypothyroidism, Congenital, Nongoitrous, 2 family:

Hypothyroidism, Congenital, Nongoitrous, 5	Hypothyroidism, Congenital, Nongoitrous, 4
Hypothyroidism, Congenital, Nongoitrous, 1	Hypothyroidism, Congenital, Nongoitrous, 3
Hypothyroidism, Congenital, Nongoitrous, 6

Diseases related to Hypothyroidism, Congenital, Nongoitrous, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 14)

#	Related Disease	Score	Top Affiliating Genes
1	hyperthyroidism, nonautoimmune	30.3	CEP128 LOC101928462 TSHR
2	hypothyroidism	29.2	GNAS TSHR
3	hypothyroidism, congenital, nongoitrous, 2	11.2
4	hypothyroidism, congenital, nongoitrous, 3	11.2
5	congenital nongoitrous hypothryoidism 1	11.2
6	pseudohypoparathyroidism, type ib	11.2
7	renal tubular acidosis	9.9
8	nephrotic syndrome	9.9
9	renal tubular acidosis, distal	9.9
10	multinodular goiter	9.8	GNAS TSHR
11	goiter	9.8	GNAS TSHR
12	hyperthyroidism, familial gestational	9.8	LOC101928462 TSHR
13	hyperthyroidism	9.7	GNAS TSHR
14	adenoma	9.6	GNAS TSHR

Graphical network of the top 20 diseases related to Hypothyroidism, Congenital, Nongoitrous, 1:

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Symptoms & Phenotypes for Hypothyroidism, Congenital, Nongoitrous, 1

Symptoms via clinical synopsis from OMIM:

⁵⁷

Endocrine Features:
euthyroidism
normal sized thyroid gland
no goiter
hypothyroidism in subset of patients
patients with hypothyroidism have hypoplastic thyroid gland

Laboratory Abnormalities:
increased serum thyroid-stimulating hormone (tsh)
normal or mildly decreased serum levels of free thyroid hormones

Immunology:
absence of anti-thyroid antibodies

Clinical features from OMIM:

275200

Human phenotypes related to Hypothyroidism, Congenital, Nongoitrous, 1:

⁵⁹ ³² (show all 15)

#	Description	HPO Frequency	Orphanet Frequency	HPO Source Accession
1	hypothyroidism ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0000821
2	muscular hypotonia ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0001252
3	constipation ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0002019
4	sleep disturbance ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0002360
5	macroglossia ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0000158
6	umbilical hernia ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0001537
7	hoarse cry ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0001615
8	feeding difficulties ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0011968
9	dry skin ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0000958
10	jaundice ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0000952
11	large fontanelles ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0000239
12	abdominal distention ⁵⁹ ³²	hallmark (90%)	Very frequent (99-80%)	HP:0003270
13	thyroid hypoplasia ³²			HP:0005990
14	congenital hypothyroidism ³²			HP:0000851
15	increased thyroid-stimulating hormone level ³²			HP:0002925

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Drugs & Therapeutics for Hypothyroidism, Congenital, Nongoitrous, 1

Search Clinical Trials , NIH Clinical Center for Hypothyroidism, Congenital, Nongoitrous, 1

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Genetic Tests for Hypothyroidism, Congenital, Nongoitrous, 1

Genetic tests related to Hypothyroidism, Congenital, Nongoitrous, 1:

#	Genetic test	Affiliating Genes
1	Hypothyroidism, Congenital, Nongoitrous, 1 ²⁹	TSHR

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Anatomical Context for Hypothyroidism, Congenital, Nongoitrous, 1

MalaCards organs/tissues related to Hypothyroidism, Congenital, Nongoitrous, 1:

⁴¹

Thyroid, Skin

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Publications for Hypothyroidism, Congenital, Nongoitrous, 1

Articles related to Hypothyroidism, Congenital, Nongoitrous, 1:

#	Title	Authors	Year
1	Nonclassic TSH resistance: TSHR mutation carriers with discrepantly high thyroidal iodine uptake. ( 21677043 )	Narumi S....Hasegawa T.	2011
2	Genetics and phenomics of hypothyroidism due to TSH resistance. ( 20083154 )	Persani L....Bonomi M.	2010
3	Thyrotropin receptor gene mutations and TSH resistance: variable expressivity in the heterozygotes. ( 16060907 )	Camilot M....TatA^ L.	2005
4	Intracellular entrapment of wild-type TSH receptor by oligomerization with mutants linked to dominant TSH resistance. ( 16135555 )	Calebiro D....Persani L.	2005
5	Paternal imprinting of Galpha(s) in the human thyroid as the basis of TSH resistance in pseudohypoparathyroidism type 1a. ( 12147228 )	Germain-Lee E.L....Levine M.A.	2002

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Genes for Hypothyroidism, Congenital, Nongoitrous, 1

Genes related to Hypothyroidism, Congenital, Nongoitrous, 1 (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	TSHR	Thyroid Stimulating Hormone Receptor	Protein Coding	1679.66	Molecular basis known ⁵⁷ Pathogenic ⁶ Causative germline mutation (loss of function) ⁵⁹ Causative variation ⁷⁵ Genetic Tests ²⁹ Novoseek inferred ⁵⁵ GeneCards inferred via : Variants (show sections)	7528344 12050212 9100579 (more) 8954020 9329388 10720030 11095460 9589691 12629076 9185526 16135555 11379397 16060907 17237844 20083154 19820021
2	GNAS	GNAS Complex Locus	Protein Coding	20.82	Novoseek inferred ⁵⁵ GeneCards inferred via : Novoseek inferred (show sections)	12970307
3	CEP128	Centrosomal Protein 128	Protein Coding	17.82	GeneCards inferred via : Variants (show sections)
4	LOC101928462	Uncharacterized LOC101928462	RNA Gene	9.26	GeneCards inferred via : Variants (show sections)

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Variations for Hypothyroidism, Congenital, Nongoitrous, 1

UniProtKB/Swiss-Prot genetic disease variations for Hypothyroidism, Congenital, Nongoitrous, 1:

⁷⁵ (show all 17)

#	Symbol	AA change	Variation ID	SNP ID
1	TSHR	p.Cys41Ser	VAR_011519
2	TSHR	p.Arg109Gln	VAR_011520
3	TSHR	p.Pro162Ala	VAR_011521	rs121908863
4	TSHR	p.Ile167Asn	VAR_011522
5	TSHR	p.Arg310Cys	VAR_011524
6	TSHR	p.Cys390Trp	VAR_011525
7	TSHR	p.Asp410Asn	VAR_011526
8	TSHR	p.Arg450His	VAR_011528
9	TSHR	p.Gly498Ser	VAR_011533
10	TSHR	p.Phe525Leu	VAR_011537
11	TSHR	p.Ala553Thr	VAR_011538
12	TSHR	p.Leu467Pro	VAR_017295
13	TSHR	p.Thr477Ile	VAR_017296
14	TSHR	p.Cys600Arg	VAR_017297
15	TSHR	p.Leu252Pro	VAR_021495
16	TSHR	p.Asn432Asp	VAR_075585
17	TSHR	p.Pro449Leu	VAR_075586

ClinVar genetic disease variations for Hypothyroidism, Congenital, Nongoitrous, 1:

⁶

(show all 36)

#	Gene	Variation	Type	Significance	SNP ID	Assembly	Location
1	TSHR	NM_000369.2(TSHR): c.500T> A (p.Ile167Asn)	single nucleotide variant	Pathogenic	rs121908862	GRCh37	Chromosome 14, 81558907: 81558907
2	TSHR	NM_000369.2(TSHR): c.500T> A (p.Ile167Asn)	single nucleotide variant	Pathogenic	rs121908862	GRCh38	Chromosome 14, 81092563: 81092563
3	TSHR	NM_000369.2(TSHR): c.484C> G (p.Pro162Ala)	single nucleotide variant	Pathogenic	rs121908863	GRCh37	Chromosome 14, 81558891: 81558891
4	TSHR	NM_000369.2(TSHR): c.484C> G (p.Pro162Ala)	single nucleotide variant	Pathogenic	rs121908863	GRCh38	Chromosome 14, 81092547: 81092547
5	TSHR	NM_000369.2(TSHR): c.326G> A (p.Arg109Gln)	single nucleotide variant	Pathogenic	rs121908865	GRCh37	Chromosome 14, 81554306: 81554306
6	TSHR	NM_000369.2(TSHR): c.326G> A (p.Arg109Gln)	single nucleotide variant	Pathogenic	rs121908865	GRCh38	Chromosome 14, 81087962: 81087962
7	TSHR	NM_000369.2(TSHR): c.970C> T (p.Gln324Ter)	single nucleotide variant	Pathogenic	rs121908867	GRCh37	Chromosome 14, 81609372: 81609372
8	TSHR	NM_000369.2(TSHR): c.970C> T (p.Gln324Ter)	single nucleotide variant	Pathogenic	rs121908867	GRCh38	Chromosome 14, 81143028: 81143028
9	TSHR	NM_000369.2(TSHR): c.1228G> A (p.Asp410Asn)	single nucleotide variant	Pathogenic	rs121908868	GRCh37	Chromosome 14, 81609630: 81609630
10	TSHR	NM_000369.2(TSHR): c.1228G> A (p.Asp410Asn)	single nucleotide variant	Pathogenic	rs121908868	GRCh38	Chromosome 14, 81143286: 81143286
11	TSHR	NM_000369.2(TSHR): c.122G> C (p.Cys41Ser)	single nucleotide variant	Pathogenic	rs121908869	GRCh37	Chromosome 14, 81422146: 81422146
12	TSHR	NM_000369.2(TSHR): c.122G> C (p.Cys41Ser)	single nucleotide variant	Pathogenic	rs121908869	GRCh38	Chromosome 14, 80955802: 80955802
13	TSHR	NM_000369.2(TSHR): c.1575C> A (p.Phe525Leu)	single nucleotide variant	Pathogenic	rs121908870	GRCh37	Chromosome 14, 81609977: 81609977
14	TSHR	NM_000369.2(TSHR): c.1575C> A (p.Phe525Leu)	single nucleotide variant	Pathogenic	rs121908870	GRCh38	Chromosome 14, 81143633: 81143633
15	TSHR	NM_000369.2(TSHR): c.1170T> G (p.Cys390Trp)	single nucleotide variant	Pathogenic	rs121908871	GRCh37	Chromosome 14, 81609572: 81609572
16	TSHR	NM_000369.2(TSHR): c.1170T> G (p.Cys390Trp)	single nucleotide variant	Pathogenic	rs121908871	GRCh38	Chromosome 14, 81143228: 81143228
17	TSHR	TSHR, 18-BP DEL, 4-BP INS	indel	Pathogenic
18	TSHR	NM_000369.2(TSHR): c.1430C> T (p.Thr477Ile)	single nucleotide variant	Pathogenic	rs121908881	GRCh37	Chromosome 14, 81609832: 81609832
19	TSHR	NM_000369.2(TSHR): c.1430C> T (p.Thr477Ile)	single nucleotide variant	Pathogenic	rs121908881	GRCh38	Chromosome 14, 81143488: 81143488
20	TSHR	NM_000369.2(TSHR): c.928C> T (p.Arg310Cys)	single nucleotide variant	Pathogenic	rs121908882	GRCh37	Chromosome 14, 81609330: 81609330
21	TSHR	NM_000369.2(TSHR): c.928C> T (p.Arg310Cys)	single nucleotide variant	Pathogenic	rs121908882	GRCh38	Chromosome 14, 81142986: 81142986
22	TSHR	NM_000369.2(TSHR): c.1798T> C (p.Cys600Arg)	single nucleotide variant	Pathogenic	rs121908884	GRCh37	Chromosome 14, 81610200: 81610200
23	TSHR	NM_000369.2(TSHR): c.1798T> C (p.Cys600Arg)	single nucleotide variant	Pathogenic	rs121908884	GRCh38	Chromosome 14, 81143856: 81143856
24	TSHR	NM_000369.2(TSHR): c.1400T> C (p.Leu467Pro)	single nucleotide variant	Pathogenic	rs121908885	GRCh37	Chromosome 14, 81609802: 81609802
25	TSHR	NM_000369.2(TSHR): c.1400T> C (p.Leu467Pro)	single nucleotide variant	Pathogenic	rs121908885	GRCh38	Chromosome 14, 81143458: 81143458
26	TSHR	TSHR, 2-BP DEL, 654AC	deletion	Pathogenic
27	TSHR	NM_000369.2(TSHR): c.545+3G> C	single nucleotide variant	Pathogenic	rs786205080	GRCh38	Chromosome 14, 81092611: 81092611
28	TSHR	NM_000369.2(TSHR): c.545+3G> C	single nucleotide variant	Pathogenic	rs786205080	GRCh37	Chromosome 14, 81558955: 81558955
29	TSHR	NM_000369.2(TSHR): c.545+2_545+3delTG	deletion	Likely pathogenic	rs786204790	GRCh37	Chromosome 14, 81558954: 81558955
30	TSHR	NM_000369.2(TSHR): c.545+2_545+3delTG	deletion	Likely pathogenic	rs786204790	GRCh38	Chromosome 14, 81092610: 81092611
31	TSHR	NM_000369.2(TSHR): c.733G> A (p.Gly245Ser)	single nucleotide variant	Uncertain significance	rs189506473	GRCh37	Chromosome 14, 81606063: 81606063
32	TSHR	NM_000369.2(TSHR): c.733G> A (p.Gly245Ser)	single nucleotide variant	Uncertain significance	rs189506473	GRCh38	Chromosome 14, 81139719: 81139719
33	TSHR	NM_000369.2(TSHR): c.1349G> A (p.Arg450His)	single nucleotide variant	Pathogenic	rs189261858	GRCh37	Chromosome 14, 81609751: 81609751
34	TSHR	NM_000369.2(TSHR): c.1349G> A (p.Arg450His)	single nucleotide variant	Pathogenic	rs189261858	GRCh38	Chromosome 14, 81143407: 81143407
35	TSHR	NM_000369.2(TSHR): c.202C> T (p.Pro68Ser)	single nucleotide variant	Likely pathogenic	rs142063461	GRCh38	Chromosome 14, 81062179: 81062179
36	TSHR	NM_000369.2(TSHR): c.202C> T (p.Pro68Ser)	single nucleotide variant	Likely pathogenic	rs142063461	GRCh37	Chromosome 14, 81528523: 81528523

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Expression for Hypothyroidism, Congenital, Nongoitrous, 1

Search GEO for disease gene expression data for Hypothyroidism, Congenital, Nongoitrous, 1.

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Pathways for Hypothyroidism, Congenital, Nongoitrous, 1

Pathways related to Hypothyroidism, Congenital, Nongoitrous, 1 according to GeneCards Suite gene sharing:

#	Super pathways	Score	Top Affiliating Genes
1	cAMP signaling pathway ³⁷ Show member pathways Hydroxycarboxylic acid-binding receptors ⁶⁶	11.56	GNAS TSHR
2	G alpha (s) signalling events ⁶⁶	11.32	GNAS TSHR
3	Human Thyroid Stimulating Hormone (TSH) signaling pathway ¹	10.79	GNAS TSHR
4	Regulation of lipolysis in adipocytes ³⁷	10.36	GNAS TSHR

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GO Terms for Hypothyroidism, Congenital, Nongoitrous, 1

Biological processes related to Hypothyroidism, Congenital, Nongoitrous, 1 according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	adenylate cyclase-activating G-protein coupled receptor signaling pathway	GO:0007189	9.16	GNAS TSHR
2	activation of adenylate cyclase activity	GO:0007190	8.96	GNAS TSHR
3	obsolete positive regulation of cAMP biosynthetic process	GO:0030819	8.62	GNAS TSHR

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⁷⁶ Wikipedia