HTNA
MCID: HYP249
MIFTS: 36

Hyperthyroidism, Nonautoimmune (HTNA)

Categories: Cardiovascular diseases, Endocrine diseases, Genetic diseases, Immune diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Hyperthyroidism, Nonautoimmune

MalaCards integrated aliases for Hyperthyroidism, Nonautoimmune:

Name: Hyperthyroidism, Nonautoimmune 56 29 13 6 39
Familial Hyperthyroidism Due to Mutations in Tsh Receptor 52 58 73
Resistance to Thyroid Stimulating Hormone 52 58 73
Familial Non-Immune Hyperthyroidism 52 58 73
Hyperthyroidism, Nonautoimmune, Autosomal Dominant 56
Hyperthyroidism Non-Autoimmune Autosomal Dominant 73
Toxic Thyroid Hyperplasia, Autosomal Dominant 56
Toxic Thyroid Hyperplasia Autosomal Dominant 73
Hyperthyroidism, Congenital Nonautoimmune 56
Hyperthyroidism Congenital Non-Autoimmune 73
Hyperthyroidism, Non-Autoimmune 73
Nonautoimmune Hyperthyroidism 52
Htna 73

Characteristics:

Orphanet epidemiological data:

58
familial hyperthyroidism due to mutations in tsh receptor
Inheritance: Autosomal dominant; Age of onset: All ages;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
de novo mutation (in some patients)
age at onset ranges from neonatal to adulthood
phenotypic variation
patients usually require total thyroidectomy
distinct disorder from transient neonatal hyperthyroidism due to maternal graves disease (see )


HPO:

31
hyperthyroidism, nonautoimmune:
Inheritance autosomal dominant inheritance sporadic


Classifications:

Orphanet: 58  
Rare circulatory system diseases
Rare renal diseases
Rare endocrine diseases


Summaries for Hyperthyroidism, Nonautoimmune

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 424 Definition A rare hyperthyroidism characterized by mild to severe hyperthyroidism, presence of goiter, absence of features of autoimmunity, frequent relapses while on treatment and a positive family history . Visit the Orphanet disease page for more resources.

MalaCards based summary : Hyperthyroidism, Nonautoimmune, also known as familial hyperthyroidism due to mutations in tsh receptor, is related to hypothyroidism, congenital, nongoitrous, 1 and hypothyroidism, congenital, nongoitrous, 5, and has symptoms including difficulty sleeping An important gene associated with Hyperthyroidism, Nonautoimmune is TSHR (Thyroid Stimulating Hormone Receptor). Affiliated tissues include thyroid, eye and bone, and related phenotypes are activating thyroid-stimulating hormone receptor defect and weight loss

UniProtKB/Swiss-Prot : 73 Hyperthyroidism, non-autoimmune: A condition characterized by abnormally high levels of serum thyroid hormones, thyroid hyperplasia, goiter and lack of anti-thyroid antibodies. Typical features of Graves disease such as exophthalmia, myxedema, antibodies anti-TSH receptor and lymphocytic infiltration of the thyroid gland are absent.

More information from OMIM: 609152

Related Diseases for Hyperthyroidism, Nonautoimmune

Diseases related to Hyperthyroidism, Nonautoimmune via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 18)
# Related Disease Score Top Affiliating Genes
1 hypothyroidism, congenital, nongoitrous, 1 31.3 TSHR CEP128
2 hypothyroidism, congenital, nongoitrous, 5 11.5
3 pseudohypoparathyroidism, type ib 11.5
4 hyperthyroidism 10.7
5 goiter 10.5
6 graves disease 1 10.4
7 helix syndrome 10.2
8 graves' disease 10.2
9 orthostatic intolerance 10.1
10 congenital hypothyroidism 10.1
11 multinodular goiter 10.1
12 plummer's disease 10.1
13 synostosis 10.1
14 nodular goiter 10.1
15 hypothyroidism 10.1
16 adenoma 10.1
17 cerebrofacial arteriovenous metameric syndrome 10.1
18 thyroid carcinoma 10.1

Graphical network of the top 20 diseases related to Hyperthyroidism, Nonautoimmune:



Diseases related to Hyperthyroidism, Nonautoimmune

Symptoms & Phenotypes for Hyperthyroidism, Nonautoimmune

Human phenotypes related to Hyperthyroidism, Nonautoimmune:

31 58 (show all 24)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 activating thyroid-stimulating hormone receptor defect 31 obligate (100%) HP:0011790
2 weight loss 58 31 hallmark (90%) Very frequent (99-80%) HP:0001824
3 goiter 58 31 hallmark (90%) Very frequent (99-80%) HP:0000853
4 diarrhea 58 31 hallmark (90%) Very frequent (99-80%) HP:0002014
5 small for gestational age 58 31 hallmark (90%) Very frequent (99-80%) HP:0001518
6 hand tremor 58 31 hallmark (90%) Very frequent (99-80%) HP:0002378
7 thyroid hyperplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008249
8 thyrotoxicosis with diffuse goiter 58 31 hallmark (90%) Very frequent (99-80%) HP:0011784
9 sleep disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0002360
10 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
11 hyperactivity 58 31 frequent (33%) Frequent (79-30%) HP:0000752
12 motor delay 58 31 frequent (33%) Frequent (79-30%) HP:0001270
13 agitation 58 31 frequent (33%) Frequent (79-30%) HP:0000713
14 accelerated skeletal maturation 58 31 frequent (33%) Frequent (79-30%) HP:0005616
15 proptosis 58 31 very rare (1%) Very rare (<4-1%) HP:0000520
16 hyperthyroidism 58 31 Obligate (100%) HP:0000836
17 intellectual disability 31 HP:0001249
18 delayed speech and language development 31 HP:0000750
19 abnormality of metabolism/homeostasis 31 HP:0001939
20 abnormal eye morphology 58 Excluded (0%)
21 premature birth 31 HP:0001622
22 tachycardia 31 HP:0001649
23 autoimmune antibody positivity 58 Excluded (0%)
24 activating thyroid-stimulating hormone receptor (tshr) defect 58 Obligate (100%)

Symptoms via clinical synopsis from OMIM:

56
Neurologic Behavioral Psychiatric Manifestations:
hyperactivity

Cardiovascular Heart:
tachycardia

Skeletal:
advanced bone age

Immunology:
absence of anti-thyroid antibodies

Skin Nails Hair Skin:
absence of dermopathy
absence of pretibial myxedema

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

Endocrine Features:
hyperthyroidism
goiter
thyroid hyperplasia
absence of immune complexes and lymphocytes in thyroid tissue

Neurologic Central Nervous System:
delayed motor development
mental retardation
delayed speech development
sleep difficulties

Growth Weight:
low birth weight

Head And Neck Eyes:
absence of exophthalmos

Prenatal Manifestations Delivery:
premature delivery of affected infants

Clinical features from OMIM:

609152

UMLS symptoms related to Hyperthyroidism, Nonautoimmune:


difficulty sleeping

Drugs & Therapeutics for Hyperthyroidism, Nonautoimmune

Search Clinical Trials , NIH Clinical Center for Hyperthyroidism, Nonautoimmune

Genetic Tests for Hyperthyroidism, Nonautoimmune

Genetic tests related to Hyperthyroidism, Nonautoimmune:

# Genetic test Affiliating Genes
1 Hyperthyroidism, Nonautoimmune 29 TSHR

Anatomical Context for Hyperthyroidism, Nonautoimmune

MalaCards organs/tissues related to Hyperthyroidism, Nonautoimmune:

40
Thyroid, Eye, Bone

Publications for Hyperthyroidism, Nonautoimmune

Articles related to Hyperthyroidism, Nonautoimmune:

(show all 22)
# Title Authors PMID Year
1
Brief report: congenital hyperthyroidism caused by a mutation in the thyrotropin-receptor gene. 56 6
7800007 1995
2
Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism. 56 6
7920658 1994
3
Familial hyperthyroidism without evidence of autoimmunity. 56 6
7124278 1982
4
Association of the TSHR gene with Graves' disease: the first disease specific locus. 6
16106256 2005
5
The first activating TSH receptor mutation in transmembrane domain 1 identified in a family with nonautoimmune hyperthyroidism. 6
11549687 2001
6
A germline mutation of the thyrotropin receptor gene associated with thyrotoxicosis and mitral valve prolapse in a Chinese family. 6
10199795 1999
7
Severe congenital hyperthyroidism caused by a germ-line neo mutation in the extracellular portion of the thyrotropin receptor. 6
9589634 1998
8
Identification of a new thyrotropin receptor germline mutation (Leu629Phe) in a family with neonatal onset of autosomal dominant nonautoimmune hyperthyroidism. 6
9398746 1997
9
The thyrotropin receptor in thyroid diseases. 56
9385128 1997
10
Sporadic congenital hyperthyroidism due to a spontaneous germline mutation in the thyrotropin receptor gene. 6
9360555 1997
11
Somatic mutations in the thyrotropin receptor gene and not in the Gs alpha protein gene in 31 toxic thyroid nodules. 6
9360556 1997
12
Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas. 6
9253356 1997
13
A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism. 56
8964822 1996
14
Congenital graves disease. Four familial cases with long-term follow-up and perspective. 56
946383 1976
15
Hereditary aspects of Graves' disease in infancy and childhood. 56
5068321 1972
16
Follow-up Findings in a Turkish Girl with Pseudohypoparathyroidism Type Ia Caused by a Novel Heterozygous Mutation in the GNAS Gene. 61
27425121 2017
17
Consecutive mutational events in a TSHR allele of Arab families with resistance to thyroid stimulating hormone. 61
22313426 2012
18
Establishment of diagnosis by bisulfite-treated methylation-specific PCR method and analysis of clinical characteristics of pseudohypoparathyroidism type 1b. 61
21836370 2011
19
Clinical heterogeneity of pseudohypoparathyroidism: from hyper- to hypocalcemia. 61
18663313 2008
20
Pseudohypoparathyroidism type 1a with congenital hypothyroidism. 61
16995592 2006
21
The syndrome of resistance to thyroid stimulating hormone. 61
14604307 2003
22
[Soluble forms of adhesion molecules sELAM-1 and sICAM-1 in Graves disease and toxic nodular goiter]. 61
14768174 2003

Variations for Hyperthyroidism, Nonautoimmune

ClinVar genetic disease variations for Hyperthyroidism, Nonautoimmune:

6 (show top 50) (show all 57) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TSHR NM_000369.2(TSHR):c.1526T>C (p.Val509Ala)SNV Pathogenic 6448 rs121908874 14:81609928-81609928 14:81143584-81143584
2 TSHR NM_000369.2(TSHR):c.2015G>A (p.Cys672Tyr)SNV Pathogenic 6449 rs121908875 14:81610417-81610417 14:81144073-81144073
3 TSHR NM_000369.2(TSHR):c.1514G>A (p.Ser505Asn)SNV Pathogenic 6450 rs121908876 14:81609916-81609916 14:81143572-81143572
4 TSHR NM_000369.2(TSHR):c.1887G>T (p.Leu629Phe)SNV Pathogenic 6451 rs121908877 14:81610289-81610289 14:81143945-81143945
5 TSHR NM_000369.2(TSHR):c.842G>A (p.Ser281Asn)SNV Pathogenic 6452 rs121908873 14:81606172-81606172 14:81139828-81139828
6 TSHR NM_000369.2(TSHR):c.1915C>T (p.Pro639Ser)SNV Pathogenic 6454 rs121908880 14:81610317-81610317 14:81143973-81143973
7 TSHR NM_000369.2(TSHR):c.1291G>A (p.Gly431Ser)SNV Pathogenic 6457 rs121908883 14:81609693-81609693 14:81143349-81143349
8 TSHR NM_000369.2(TSHR):c.1891T>C (p.Phe631Leu)SNV Pathogenic 6433 rs121908861 14:81610293-81610293 14:81143949-81143949
9 TSHR NM_000369.2(TSHR):c.1358T>C (p.Met453Thr)SNV Pathogenic 6436 rs121908864 14:81609760-81609760 14:81143416-81143416
10 TSHR NM_000369.2(TSHR):c.1637G>A (p.Trp546Ter)SNV Conflicting interpretations of pathogenicity 6439 rs121908866 14:81610039-81610039 14:81143695-81143695
11 TSHR NM_000369.2(TSHR):c.1657G>A (p.Ala553Thr)SNV Conflicting interpretations of pathogenicity 6445 rs121908872 14:81610059-81610059 14:81143715-81143715
12 TSHR NM_000369.2(TSHR):c.394G>C (p.Gly132Arg)SNV Conflicting interpretations of pathogenicity 314693 rs760874290 14:81557414-81557414 14:81091070-81091070
13 TSHR NM_000369.2(TSHR):c.2120G>A (p.Arg707Gln)SNV Uncertain significance 314698 rs368452281 14:81610522-81610522 14:81144178-81144178
14 TSHR NM_000369.2(TSHR):c.*116G>ASNV Uncertain significance 314700 rs554104473 14:81610813-81610813 14:81144469-81144469
15 TSHR NM_000369.2(TSHR):c.*400T>CSNV Uncertain significance 314707 rs143040631 14:81611097-81611097 14:81144753-81144753
16 TSHR NM_000369.2(TSHR):c.*1946C>TSNV Uncertain significance 314726 rs187891791 14:81612643-81612643 14:81146299-81146299
17 TSHR NM_000369.2(TSHR):c.157A>C (p.Ser53Arg)SNV Uncertain significance 314690 rs886050853 14:81422181-81422181 14:80955837-80955837
18 TSHR NM_000369.2(TSHR):c.1191G>T (p.Val397=)SNV Uncertain significance 314696 rs781406064 14:81609593-81609593 14:81143249-81143249
19 TSHR NM_000369.2(TSHR):c.*125A>GSNV Uncertain significance 314701 rs886050855 14:81610822-81610822 14:81144478-81144478
20 TSHR NM_000369.2(TSHR):c.*137delGdeletion Uncertain significance 314702 rs886050856 14:81610834-81610834 14:81144490-81144490
21 TSHR NM_000369.2(TSHR):c.*1695T>CSNV Uncertain significance 314722 rs112187344 14:81612392-81612392 14:81146048-81146048
22 TSHR NM_000369.2(TSHR):c.*1317C>ASNV Uncertain significance 314718 rs886050859 14:81612014-81612014 14:81145670-81145670
23 TSHR NM_000369.2(TSHR):c.*1898A>GSNV Uncertain significance 314725 rs886050862 14:81612595-81612595 14:81146251-81146251
24 TSHR NM_000369.2(TSHR):c.*1620C>GSNV Uncertain significance 314721 rs886050860 14:81612317-81612317 14:81145973-81145973
25 TSHR NM_000369.2(TSHR):c.*1742G>TSNV Uncertain significance 314723 rs886050861 14:81612439-81612439 14:81146095-81146095
26 TSHR NM_000369.2(TSHR):c.-60G>ASNV Uncertain significance 314689 rs201252762 14:81421965-81421965 14:80955621-80955621
27 TSHR NM_000369.2(TSHR):c.171-11T>CSNV Uncertain significance 314691 rs145265345 14:81528481-81528481 14:81062137-81062137
28 TSHR NM_000369.2(TSHR):c.615-6C>GSNV Uncertain significance 314694 rs886050854 14:81574713-81574713 14:81108369-81108369
29 TSHR NM_000369.2(TSHR):c.692+3G>ASNV Uncertain significance 314695 rs552128204 14:81574799-81574799 14:81108455-81108455
30 TSHR NM_000369.2(TSHR):c.2161G>T (p.Val721Phe)SNV Uncertain significance 135399 rs61745409 14:81610563-81610563 14:81144219-81144219
31 TSHR NM_000369.2(TSHR):c.1290G>A (p.Leu430=)SNV Uncertain significance 314697 rs375393735 14:81609692-81609692 14:81143348-81143348
32 TSHR NM_000369.2(TSHR):c.*319G>ASNV Uncertain significance 314706 rs886050857 14:81611016-81611016 14:81144672-81144672
33 TSHR NM_000369.2(TSHR):c.357T>A (p.Pro119=)SNV Uncertain significance 314692 rs144084915 14:81554337-81554337 14:81087993-81087993
34 TSHR NM_000369.2(TSHR):c.*1154dupTduplication Likely benign 314715 rs3214569 14:81611851-81611851 14:81145507-81145507
35 TSHR NM_000369.2(TSHR):c.*18C>ASNV Likely benign 314699 rs77789619 14:81610715-81610715 14:81144371-81144371
36 TSHR NM_000369.2(TSHR):c.*1152T>ASNV Likely benign 314714 rs2288494 14:81611849-81611849 14:81145505-81145505
37 TSHR NM_000369.2(TSHR):c.*1222G>CSNV Likely benign 314716 rs2288495 14:81611919-81611919 14:81145575-81145575
38 TSHR NM_000369.2(TSHR):c.*1289A>GSNV Likely benign 314717 rs150122093 14:81611986-81611986 14:81145642-81145642
39 TSHR NM_000369.2(TSHR):c.881+3A>GSNV Likely benign 218440 rs186091357 14:81606214-81606214 14:81139870-81139870
40 TSHR NM_000369.2(TSHR):c.2232C>G (p.Asn744Lys)SNV Likely benign 135396 rs61743974 14:81610634-81610634 14:81144290-81144290
41 TSHR NM_000369.2(TSHR):c.*1417T>CSNV Likely benign 314719 rs2288496 14:81612114-81612114 14:81145770-81145770
42 TSHR NM_000369.2(TSHR):c.*1580A>GSNV Likely benign 314720 rs189084497 14:81612277-81612277 14:81145933-81145933
43 TSHR NM_000369.2(TSHR):c.*1813T>ASNV Likely benign 314724 rs58832257 14:81612510-81612510 14:81146166-81146166
44 TSHR NM_000369.2(TSHR):c.*245C>TSNV Likely benign 314705 rs7144481 14:81610942-81610942 14:81144598-81144598
45 TSHR NM_000369.2(TSHR):c.*431T>CSNV Likely benign 314708 rs17630128 14:81611128-81611128 14:81144784-81144784
46 TSHR NM_000369.2(TSHR):c.*960T>CSNV Likely benign 314712 rs142517342 14:81611657-81611657 14:81145313-81145313
47 TSHR NM_000369.2(TSHR):c.*1106G>TSNV Likely benign 314713 rs150923034 14:81611803-81611803 14:81145459-81145459
48 TSHR NM_000369.2(TSHR):c.*474G>TSNV Likely benign 314709 rs61266735 14:81611171-81611171 14:81144827-81144827
49 TSHR NM_000369.2(TSHR):c.*728A>GSNV Likely benign 314710 rs73342245 14:81611425-81611425 14:81145081-81145081
50 TSHR NM_000369.2(TSHR):c.*909C>TSNV Likely benign 314711 rs2288493 14:81611606-81611606 14:81145262-81145262

UniProtKB/Swiss-Prot genetic disease variations for Hyperthyroidism, Nonautoimmune:

73 (show all 21)
# Symbol AA change Variation ID SNP ID
1 TSHR p.Ser281Asn VAR_003570
2 TSHR p.Ser505Asn VAR_003571
3 TSHR p.Leu629Phe VAR_003575
4 TSHR p.Gly431Ser VAR_011527
5 TSHR p.Met453Thr VAR_011529
6 TSHR p.Met463Val VAR_011530
7 TSHR p.Ile486Phe VAR_011531
8 TSHR p.Ile486Met VAR_011532
9 TSHR p.Ser505Arg VAR_011534
10 TSHR p.Val509Ala VAR_011535
11 TSHR p.Ile568Thr VAR_011539
12 TSHR p.Phe631Leu VAR_011545
13 TSHR p.Thr632Ala VAR_011546
14 TSHR p.Thr632Ile VAR_011547
15 TSHR p.Asp633Glu VAR_011549
16 TSHR p.Pro639Ser VAR_011552
17 TSHR p.Ala647Val VAR_011553
18 TSHR p.Asn650Tyr VAR_011554
19 TSHR p.Asn670Ser VAR_011556
20 TSHR p.Cys672Tyr VAR_011557
21 TSHR p.Val597Phe VAR_021499

Expression for Hyperthyroidism, Nonautoimmune

Search GEO for disease gene expression data for Hyperthyroidism, Nonautoimmune.

Pathways for Hyperthyroidism, Nonautoimmune

GO Terms for Hyperthyroidism, Nonautoimmune

Sources for Hyperthyroidism, Nonautoimmune

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