HTNA
MCID: HYP249
MIFTS: 32

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 58 30 13 6 41
Familial Hyperthyroidism Due to Mutations in Tsh Receptor 60 76
Resistance to Thyroid Stimulating Hormone 60 76
Familial Non-Immune Hyperthyroidism 60 76
Hyperthyroidism, Nonautoimmune, Autosomal Dominant 58
Hyperthyroidism Non-Autoimmune Autosomal Dominant 76
Toxic Thyroid Hyperplasia, Autosomal Dominant 58
Toxic Thyroid Hyperplasia Autosomal Dominant 76
Hyperthyroidism, Congenital Nonautoimmune 58
Hyperthyroidism Congenital Non-Autoimmune 76
Hyperthyroidism, Non-Autoimmune 76
Htna 76

Characteristics:

Orphanet epidemiological data:

60
familial hyperthyroidism due to mutations in tsh receptor
Inheritance: Autosomal dominant; Age of onset: All ages;

OMIM:

58
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:

33
hyperthyroidism, nonautoimmune:
Inheritance autosomal dominant inheritance sporadic


Classifications:



Summaries for Hyperthyroidism, Nonautoimmune

UniProtKB/Swiss-Prot : 76 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.

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

Description from OMIM: 609152

Related Diseases for Hyperthyroidism, Nonautoimmune

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

# Related Disease Score Top Affiliating Genes
1 hypothyroidism, congenital, nongoitrous, 1 31.7 CEP128 TSHR
2 familial hyperthyroidism due to mutations in tsh receptor 11.6
3 hypothyroidism, congenital, nongoitrous, 5 11.3
4 pseudohypoparathyroidism, type ib 11.3
5 hyperthyroidism, familial gestational 9.6 LOC101928462 TSHR

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:

60 33 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperthyroidism 60 33 Obligate (100%) HP:0000836
2 goiter 60 33 Very frequent (99-80%) HP:0000853
3 motor delay 60 33 Frequent (79-30%) HP:0001270
4 accelerated skeletal maturation 60 33 Frequent (79-30%) HP:0005616
5 hyperactivity 60 33 Frequent (79-30%) HP:0000752
6 small for gestational age 60 33 Very frequent (99-80%) HP:0001518
7 thyroid hyperplasia 60 33 Very frequent (99-80%) HP:0008249
8 intellectual disability 33 HP:0001249
9 sleep disturbance 60 Frequent (79-30%)
10 global developmental delay 60 Frequent (79-30%)
11 delayed speech and language development 33 HP:0000750
12 abnormality of metabolism/homeostasis 33 HP:0001939
13 weight loss 60 Very frequent (99-80%)
14 agitation 60 Frequent (79-30%)
15 diarrhea 60 Very frequent (99-80%)
16 proptosis 60 Very rare (<4-1%)
17 premature birth 33 HP:0001622
18 tachycardia 33 HP:0001649
19 autoimmune antibody positivity 60 Excluded (0%)
20 hand tremor 60 Very frequent (99-80%)
21 activating thyroid-stimulating hormone receptor (tshr) defect 60 Obligate (100%)
22 thyrotoxicosis with diffuse goiter 60 Very frequent (99-80%)
23 abnormal eye morphology 60 Excluded (0%)

Symptoms via clinical synopsis from OMIM:

58
Endocrine Features:
hyperthyroidism
goiter
thyroid hyperplasia
absence of immune complexes and lymphocytes in thyroid tissue

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

Neurologic Behavioral Psychiatric Manifestations:
hyperactivity

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 30 TSHR

Anatomical Context for Hyperthyroidism, Nonautoimmune

MalaCards organs/tissues related to Hyperthyroidism, Nonautoimmune:

42
Thyroid, Bone, Eye

Publications for Hyperthyroidism, Nonautoimmune

Articles related to Hyperthyroidism, Nonautoimmune:

(show all 13)
# Title Authors Year
1
Consecutive mutational events in a TSHR allele of Arab families with resistance to thyroid stimulating hormone. ( 22313426 )
2012
2
Association of the TSHR gene with Graves' disease: the first disease specific locus. ( 16106256 )
2005
3
The syndrome of resistance to thyroid stimulating hormone. ( 14604307 )
2003
4
The first activating TSH receptor mutation in transmembrane domain 1 identified in a family with nonautoimmune hyperthyroidism. ( 11549687 )
2001
5
A germline mutation of the thyrotropin receptor gene associated with thyrotoxicosis and mitral valve prolapse in a Chinese family. ( 10199795 )
1999
6
Severe congenital hyperthyroidism caused by a germ-line neo mutation in the extracellular portion of the thyrotropin receptor. ( 9589634 )
1998
7
Sporadic congenital hyperthyroidism due to a spontaneous germline mutation in the thyrotropin receptor gene. ( 9360555 )
1997
8
Identification of a new thyrotropin receptor germline mutation (Leu629Phe) in a family with neonatal onset of autosomal dominant nonautoimmune hyperthyroidism. ( 9398746 )
1997
9
Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas. ( 9253356 )
1997
10
Somatic mutations in the thyrotropin receptor gene and not in the Gs alpha protein gene in 31 toxic thyroid nodules. ( 9360556 )
1997
11
Brief report: congenital hyperthyroidism caused by a mutation in the thyrotropin-receptor gene. ( 7800007 )
1995
12
Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism. ( 7920658 )
1994
13
Familial hyperthyroidism without evidence of autoimmunity. ( 7124278 )
1982

Variations for Hyperthyroidism, Nonautoimmune

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

76 (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

ClinVar genetic disease variations for Hyperthyroidism, Nonautoimmune:

6 (show top 50) (show all 114)
# Gene Variation Type Significance SNP ID Assembly Location
1 TSHR NM_000369.2(TSHR): c.106G> C (p.Asp36His) single nucleotide variant Benign/Likely benign rs61747482 GRCh37 Chromosome 14, 81422130: 81422130
2 TSHR NM_000369.2(TSHR): c.106G> C (p.Asp36His) single nucleotide variant Benign/Likely benign rs61747482 GRCh38 Chromosome 14, 80955786: 80955786
3 TSHR NM_000369.2(TSHR): c.1891T> C (p.Phe631Leu) single nucleotide variant Pathogenic rs121908861 GRCh37 Chromosome 14, 81610293: 81610293
4 TSHR NM_000369.2(TSHR): c.1891T> C (p.Phe631Leu) single nucleotide variant Pathogenic rs121908861 GRCh38 Chromosome 14, 81143949: 81143949
5 TSHR NM_000369.2(TSHR): c.1358T> C (p.Met453Thr) single nucleotide variant Pathogenic rs121908864 GRCh37 Chromosome 14, 81609760: 81609760
6 TSHR NM_000369.2(TSHR): c.1358T> C (p.Met453Thr) single nucleotide variant Pathogenic rs121908864 GRCh38 Chromosome 14, 81143416: 81143416
7 TSHR NM_000369.2(TSHR): c.1637G> A (p.Trp546Ter) single nucleotide variant Conflicting interpretations of pathogenicity rs121908866 GRCh37 Chromosome 14, 81610039: 81610039
8 TSHR NM_000369.2(TSHR): c.1637G> A (p.Trp546Ter) single nucleotide variant Conflicting interpretations of pathogenicity rs121908866 GRCh38 Chromosome 14, 81143695: 81143695
9 TSHR NM_000369.2(TSHR): c.1657G> A (p.Ala553Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs121908872 GRCh37 Chromosome 14, 81610059: 81610059
10 TSHR NM_000369.2(TSHR): c.1657G> A (p.Ala553Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs121908872 GRCh38 Chromosome 14, 81143715: 81143715
11 TSHR NM_000369.2(TSHR): c.1526T> C (p.Val509Ala) single nucleotide variant Pathogenic rs121908874 GRCh37 Chromosome 14, 81609928: 81609928
12 TSHR NM_000369.2(TSHR): c.1526T> C (p.Val509Ala) single nucleotide variant Pathogenic rs121908874 GRCh38 Chromosome 14, 81143584: 81143584
13 TSHR NM_000369.2(TSHR): c.2015G> A (p.Cys672Tyr) single nucleotide variant Pathogenic rs121908875 GRCh37 Chromosome 14, 81610417: 81610417
14 TSHR NM_000369.2(TSHR): c.2015G> A (p.Cys672Tyr) single nucleotide variant Pathogenic rs121908875 GRCh38 Chromosome 14, 81144073: 81144073
15 TSHR NM_000369.2(TSHR): c.1514G> A (p.Ser505Asn) single nucleotide variant Pathogenic rs121908876 GRCh37 Chromosome 14, 81609916: 81609916
16 TSHR NM_000369.2(TSHR): c.1514G> A (p.Ser505Asn) single nucleotide variant Pathogenic rs121908876 GRCh38 Chromosome 14, 81143572: 81143572
17 TSHR NM_000369.2(TSHR): c.1887G> T (p.Leu629Phe) single nucleotide variant Pathogenic rs121908877 GRCh37 Chromosome 14, 81610289: 81610289
18 TSHR NM_000369.2(TSHR): c.1887G> T (p.Leu629Phe) single nucleotide variant Pathogenic rs121908877 GRCh38 Chromosome 14, 81143945: 81143945
19 TSHR NM_000369.2(TSHR): c.842G> A (p.Ser281Asn) single nucleotide variant Pathogenic rs121908873 GRCh37 Chromosome 14, 81606172: 81606172
20 TSHR NM_000369.2(TSHR): c.842G> A (p.Ser281Asn) single nucleotide variant Pathogenic rs121908873 GRCh38 Chromosome 14, 81139828: 81139828
21 TSHR NM_000369.2(TSHR): c.1915C> T (p.Pro639Ser) single nucleotide variant Pathogenic rs121908880 GRCh37 Chromosome 14, 81610317: 81610317
22 TSHR NM_000369.2(TSHR): c.1915C> T (p.Pro639Ser) single nucleotide variant Pathogenic rs121908880 GRCh38 Chromosome 14, 81143973: 81143973
23 TSHR NM_000369.2(TSHR): c.1291G> A (p.Gly431Ser) single nucleotide variant Pathogenic rs121908883 GRCh37 Chromosome 14, 81609693: 81609693
24 TSHR NM_000369.2(TSHR): c.1291G> A (p.Gly431Ser) single nucleotide variant Pathogenic rs121908883 GRCh38 Chromosome 14, 81143349: 81143349
25 TSHR NM_000369.2(TSHR): c.2232C> G (p.Asn744Lys) single nucleotide variant Likely benign rs61743974 GRCh37 Chromosome 14, 81610634: 81610634
26 TSHR NM_000369.2(TSHR): c.2232C> G (p.Asn744Lys) single nucleotide variant Likely benign rs61743974 GRCh38 Chromosome 14, 81144290: 81144290
27 TSHR NM_000369.2(TSHR): c.2161G> T (p.Val721Phe) single nucleotide variant Uncertain significance rs61745409 GRCh38 Chromosome 14, 81144219: 81144219
28 TSHR NM_000369.2(TSHR): c.2161G> T (p.Val721Phe) single nucleotide variant Uncertain significance rs61745409 GRCh37 Chromosome 14, 81610563: 81610563
29 TSHR NM_000369.2(TSHR): c.2181G> C (p.Glu727Asp) single nucleotide variant Benign/Likely benign rs1991517 GRCh38 Chromosome 14, 81144239: 81144239
30 TSHR NM_000369.2(TSHR): c.2181G> C (p.Glu727Asp) single nucleotide variant Benign/Likely benign rs1991517 GRCh37 Chromosome 14, 81610583: 81610583
31 TSHR NM_000369.2(TSHR): c.881+3A> G single nucleotide variant Likely benign rs186091357 GRCh38 Chromosome 14, 81139870: 81139870
32 TSHR NM_000369.2(TSHR): c.881+3A> G single nucleotide variant Likely benign rs186091357 GRCh37 Chromosome 14, 81606214: 81606214
33 TSHR NM_000369.2(TSHR): c.545+13A> G single nucleotide variant Benign/Likely benign rs2241119 GRCh37 Chromosome 14, 81558965: 81558965
34 TSHR NM_000369.2(TSHR): c.545+13A> G single nucleotide variant Benign/Likely benign rs2241119 GRCh38 Chromosome 14, 81092621: 81092621
35 TSHR NM_000369.2(TSHR): c.561T> C (p.Asn187=) single nucleotide variant Benign/Likely benign rs2075179 GRCh38 Chromosome 14, 81096654: 81096654
36 TSHR NM_000369.2(TSHR): c.561T> C (p.Asn187=) single nucleotide variant Benign/Likely benign rs2075179 GRCh37 Chromosome 14, 81562998: 81562998
37 TSHR NM_000369.2(TSHR): c.1377G> A (p.Ala459=) single nucleotide variant Benign/Likely benign rs113951800 GRCh38 Chromosome 14, 81143435: 81143435
38 TSHR NM_000369.2(TSHR): c.1377G> A (p.Ala459=) single nucleotide variant Benign/Likely benign rs113951800 GRCh37 Chromosome 14, 81609779: 81609779
39 TSHR NM_000369.2(TSHR): c.1290G> A (p.Leu430=) single nucleotide variant Uncertain significance rs375393735 GRCh38 Chromosome 14, 81143348: 81143348
40 TSHR NM_000369.2(TSHR): c.1290G> A (p.Leu430=) single nucleotide variant Uncertain significance rs375393735 GRCh37 Chromosome 14, 81609692: 81609692
41 TSHR NM_000369.2(TSHR): c.*18C> A single nucleotide variant Likely benign rs77789619 GRCh38 Chromosome 14, 81144371: 81144371
42 TSHR NM_000369.2(TSHR): c.*18C> A single nucleotide variant Likely benign rs77789619 GRCh37 Chromosome 14, 81610715: 81610715
43 TSHR NM_000369.2(TSHR): c.*319G> A single nucleotide variant Uncertain significance rs886050857 GRCh38 Chromosome 14, 81144672: 81144672
44 TSHR NM_000369.2(TSHR): c.*319G> A single nucleotide variant Uncertain significance rs886050857 GRCh37 Chromosome 14, 81611016: 81611016
45 TSHR NM_000369.2(TSHR): c.*1154dupT duplication Likely benign rs3214569 GRCh37 Chromosome 14, 81611851: 81611851
46 TSHR NM_000369.2(TSHR): c.*1154dupT duplication Likely benign rs3214569 GRCh38 Chromosome 14, 81145507: 81145507
47 TSHR NM_000369.2(TSHR): c.*1620C> G single nucleotide variant Uncertain significance rs886050860 GRCh38 Chromosome 14, 81145973: 81145973
48 TSHR NM_000369.2(TSHR): c.*1620C> G single nucleotide variant Uncertain significance rs886050860 GRCh37 Chromosome 14, 81612317: 81612317
49 TSHR NM_000369.2(TSHR): c.*1742G> T single nucleotide variant Uncertain significance rs886050861 GRCh38 Chromosome 14, 81146095: 81146095
50 TSHR NM_000369.2(TSHR): c.*1742G> T single nucleotide variant Uncertain significance rs886050861 GRCh37 Chromosome 14, 81612439: 81612439

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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