GRTH
MCID: THY114
MIFTS: 31

Thyroid Hormone Resistance, Generalized, Autosomal Recessive (GRTH)

Categories: Endocrine diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Thyroid Hormone Resistance, Generalized, Autosomal Recessive

MalaCards integrated aliases for Thyroid Hormone Resistance, Generalized, Autosomal Recessive:

Name: Thyroid Hormone Resistance, Generalized, Autosomal Recessive 56 29 6 39 71
Thyroid Hormone Resistance, Autosomal Recessive 56 13
Thyroid Hormone Resistance, Generalized, Autosomal Dominant 71
Generalized Thyroid Hormone Resistance Autosomal Recessive 73
Thyroid Hormone Resistance Syndrome 71
Thyroid Hormone Unresponsiveness 56
Refetoff Syndrome 56
Gthrar 73
Grth 56
Gthr 56

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive


HPO:

31
thyroid hormone resistance, generalized, autosomal recessive:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Thyroid Hormone Resistance, Generalized, Autosomal Recessive

UniProtKB/Swiss-Prot : 73 Generalized thyroid hormone resistance autosomal recessive: An autosomal recessive disorder characterized by goiter, clinical euthyroidism, end-organ unresponsiveness to thyroid hormone, abnormal growth and bone maturation, and deafness. Patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone.

MalaCards based summary : Thyroid Hormone Resistance, Generalized, Autosomal Recessive, also known as thyroid hormone resistance, autosomal recessive, is related to thyroid hormone resistance, generalized, autosomal dominant and generalized resistance to thyroid hormone. An important gene associated with Thyroid Hormone Resistance, Generalized, Autosomal Recessive is THRB (Thyroid Hormone Receptor Beta). Affiliated tissues include thyroid, bone and pituitary, and related phenotypes are hearing impairment and epiphyseal stippling

More information from OMIM: 274300

Related Diseases for Thyroid Hormone Resistance, Generalized, Autosomal Recessive

Diseases in the Generalized Resistance to Thyroid Hormone family:

Thyroid Hormone Resistance, Generalized, Autosomal Dominant Thyroid Hormone Resistance, Generalized, Autosomal Recessive

Diseases related to Thyroid Hormone Resistance, Generalized, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(showing 20, show less)
# Related Disease Score Top Affiliating Genes
1 thyroid hormone resistance, generalized, autosomal dominant 11.7
2 generalized resistance to thyroid hormone 11.7
3 thyroid hormone resistance, selective pituitary 11.3
4 azoospermia 10.3
5 papillomatosis, confluent and reticulated 10.3
6 graves disease 1 10.2
7 male infertility 10.2
8 graves' disease 10.2
9 infertility 10.2
10 orthostatic intolerance 10.1
11 atrial fibrillation 10.1
12 primary hyperparathyroidism 10.1
13 goiter 10.1
14 hyperparathyroidism 10.1
15 pituitary tumors 10.1
16 tremor 10.1
17 congenital hypothyroidism 9.9
18 hypothyroidism 9.9
19 exophthalmos 9.9
20 cardiogenic shock 9.9

Graphical network of the top 20 diseases related to Thyroid Hormone Resistance, Generalized, Autosomal Recessive:



Diseases related to Thyroid Hormone Resistance, Generalized, Autosomal Recessive

Symptoms & Phenotypes for Thyroid Hormone Resistance, Generalized, Autosomal Recessive

Human phenotypes related to Thyroid Hormone Resistance, Generalized, Autosomal Recessive:

31 (showing 6, show less)
# Description HPO Frequency HPO Source Accession
1 hearing impairment 31 HP:0000365
2 epiphyseal stippling 31 HP:0010655
3 goiter 31 HP:0000853
4 proptosis 31 HP:0000520
5 small for gestational age 31 HP:0001518
6 impaired sensitivity to thyroid hormone 31 HP:0002930

Symptoms via clinical synopsis from OMIM:

56
Neck:
goiter

Ears:
congenital deafness

Endocrine:
end-organ unresponsiveness to thyroid hormone
thyroid hormone receptor-beta gene (thr1) deletion
clinical euthyroidism

Misc:
low birth weight for dates

Eyes:
exophthalmos

Skel:
stippled epiphyses

Lab:
abnormally high pbi
elevated blood thyroid hormones
elevated thyrotropin
normal response to thyrotropin-releasing hormone

Clinical features from OMIM:

274300

Drugs & Therapeutics for Thyroid Hormone Resistance, Generalized, Autosomal Recessive

Interventional clinical trials:

(showing 1, show less)
# Name Status NCT ID Phase Drugs
1 The Prevalence of Hearing Loss Among Children With Congenital Hypothyroidism Withdrawn NCT01223638

Search NIH Clinical Center for Thyroid Hormone Resistance, Generalized, Autosomal Recessive

Genetic Tests for Thyroid Hormone Resistance, Generalized, Autosomal Recessive

Genetic tests related to Thyroid Hormone Resistance, Generalized, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Thyroid Hormone Resistance, Generalized, Autosomal Recessive 29 THRB

Anatomical Context for Thyroid Hormone Resistance, Generalized, Autosomal Recessive

MalaCards organs/tissues related to Thyroid Hormone Resistance, Generalized, Autosomal Recessive:

40
Thyroid, Bone, Pituitary, Testis

Publications for Thyroid Hormone Resistance, Generalized, Autosomal Recessive

Articles related to Thyroid Hormone Resistance, Generalized, Autosomal Recessive:

(showing 102, show less)
# Title Authors PMID Year
1
Screening of nineteen unrelated families with generalized resistance to thyroid hormone for known point mutations in the thyroid hormone receptor beta gene and the detection of a new mutation. 61 56 6
1991834 1991
2
Familial syndrome combining deaf-mutism, stuppled epiphyses, goiter and abnormally high PBI: possible target organ refractoriness to thyroid hormone. 56 6
4163616 1967
3
Homozygosity for a dominant negative thyroid hormone receptor gene responsible for generalized resistance to thyroid hormone. 61 6
1682340 1991
4
A new mutation in the thyroid hormone receptor (TR) beta gene (V458A) in a family with resistance to thyroid hormone (RTH). 6
8875752 1996
5
Nomenclature of thyroid hormone receptor beta gene mutations in resistance to thyroid hormone: consensus statement from the First Workshop on Thyroid Hormone Resistance, 10-11 July 1993, Cambridge, UK. 6
8013151 1994
6
A homozygous deletion in the c-erbA beta thyroid hormone receptor gene in a patient with generalized thyroid hormone resistance: isolation and characterization of the mutant receptor. 6
1653889 1991
7
Thyroid hormone action at the nuclear level. 56
2982308 1985
8
Thyroid hormone unresponsiveness in two siblings with intrauterine growth retardation exophthalmos. 56
6538138 1984
9
Syndromes of thyroid hormone resistance. 56
6287848 1982
10
Defective thyroid hormone feedback regulation in the syndrome of peripheral resistance to thyroid hormone. 56
6769941 1980
11
Nuclear receptors for thyroid hormone: evidence for nonrandom distribution within chromatin. 56
168576 1975
12
Partial target organ resistance to thyroid hormone. 56
4632689 1973
13
Congenital euthyroid goitre and partial peripheral resistance to thyroid hormones. 56
4123403 1973
14
Studies of a sibship with apparent hereditary resistance to the intracellular action of thyroid hormone. 56
5047916 1972
15
Targeted Knock-In Mice with a Human Mutation in GRTH/DDX25 Reveals the Essential Role of Phosphorylated GRTH in Spermatid Development during Spermatogenesis. 61
31009948 2019
16
Characterization of the Phosphorylation Site of GRTH/DDX25 and Protein Kinase A Binding Interface Provides Structural Basis for the Design of a Non-Hormonal Male Contraceptive. 61
31040297 2019
17
Gonadotropin Regulation Testicular RNA Helicase, Two Decades of Studies on Its Structure Function and Regulation From Its Discovery Opens a Window for Development of a Non-hormonal Oral Male Contraceptive. 61
31555207 2019
18
Allethrin toxicity causes reproductive dysfunction in male rats. 61
28181402 2017
19
Germ Cell Nuclear Factor (GCNF/RTR) Regulates Transcription of Gonadotropin-Regulated Testicular RNA Helicase (GRTH/DDX25) in Testicular Germ Cells--The Androgen Connection. 61
26484580 2015
20
Elucidation of RNA binding regions of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) to transcripts of a chromatin remodeling protein essential for spermatogenesis. 61
25910401 2015
21
Association of the gonadotrophin-regulated testicular RNA helicase gene polymorphism with human male infertility. 61
24168058 2014
22
Connecting cis-elements and trans-factors with mechanisms of developmental regulation of mRNA translation in meiotic and haploid mammalian spermatogenic cells. 61
23579190 2013
23
A 5'-flanking region of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) gene directs its cell-specific androgen-regulated gene expression in testicular germ cells. 61
23546600 2013
24
GRTH: a key to understanding androgen-mediated germ cell signaling. 61
23687113 2013
25
Androgen-induced activation of gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) transcription: essential role of a nonclassical androgen response element half-site. 61
22331472 2012
26
Expression of DDX25 in nuage components of mammalian spermatogenic cells: immunofluorescence and immunoelectron microscopic study. 61
22038044 2012
27
Role of gonadotropin regulated testicular RNA helicase (GRTH/Ddx25) on polysomal associated mRNAs in mouse testis. 61
22479328 2012
28
Testis-specific miRNA-469 up-regulated in gonadotropin-regulated testicular RNA helicase (GRTH/DDX25)-null mice silences transition protein 2 and protamine 2 messages at sites within coding region: implications of its role in germ cell development. 61
22086916 2011
29
Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), a negative regulator of luteinizing/chorionic gonadotropin hormone-induced steroidogenesis in Leydig cells: central role of steroidogenic acute regulatory protein (StAR). 61
21719703 2011
30
Gonadotropin-regulated testicular helicase (GRTH/DDX25): a master post-transcriptional regulator of spermatogenesis. 61
21691948 2011
31
Relevance of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) in the structural integrity of the chromatoid body during spermatogenesis. 61
20176059 2010
32
Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) gene: cell-specific expression and transcriptional regulation by androgen in transgenic mouse testis. 61
20108248 2010
33
Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25): a multifunctional protein essential for spermatogenesis. 61
19875492 2010
34
Differences in gonadotropin-regulated testicular helicase (GRTH/DDX25) single nucleotide polymorphism between Japanese and Chinese populations. 61
18487219 2008
35
Gonadotropin-regulated testicular helicase (DDX25), an essential regulator of spermatogenesis, prevents testicular germ cell apoptosis. 61
18430733 2008
36
Polymorphism of the GRTH/DDX25 gene in normal and infertile Japanese men: a missense mutation associated with loss of GRTH phosphorylation. 61
17848414 2007
37
Evaluation of thyroid hormone action in a case of generalized resistance to thyroid hormone with chronic thyroiditis: discovery of a novel heterozygous missense mutation (G347A). 61
17827792 2007
38
Gonadotropin-regulated testicular helicase (GRTH/DDX25): an essential regulator of spermatogenesis. 61
17889551 2007
39
Thyroid hormone resistance. 61
17132274 2006
40
Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is a transport protein involved in gene-specific mRNA export and protein translation during spermatogenesis. 61
16968703 2006
41
Single nucleotide polymorphisms of the gonadotrophin-regulated testicular helicase (GRTH) gene may be associated with the human spermatogenesis impairment. 61
16293649 2006
42
The role of polyhalogenated aromatic hydrocarbons on thyroid hormone disruption and cognitive function: a review. 61
15573475 2004
43
Genomic organization and transcriptional analysis of gonadotropin-regulated testicular RNA helicase--GRTH/DDX25 gene. 61
15094194 2004
44
Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is essential for spermatid development and completion of spermatogenesis. 61
15096601 2004
45
Successful therapy with L-T4 in a 5 year-old boy with generalized thyroid hormone resistance. 61
14513884 2003
46
Cell-specific and hormone-regulated expression of gonadotropin-regulated testicular RNA helicase gene (GRTH/Ddx25) resulting from alternative utilization of translation initiation codons in the rat testis. 61
12734186 2003
47
Atrial fibrillation and mitral prolapse in a subject affected by Refetoff syndrome. 61
12032470 2002
48
Genetic analyses and evaluation of peripheral parameters of thyroid hormone action for the differential diagnosis of RTH. A novel heterozygous missense mutation (M334T) discovered. 61
11929097 2002
49
Resistance to thyroid hormone, and peroxisome-proliferator-activated receptor gamma resistance. 61
11356159 2001
50
Regulation of steroidogenic enzymes and a novel testicular RNA helicase. 61
11384877 2001
51
Abnormally high TSH in subject with thyrotoxicosis affected by congenital hypothyroidism. Case report. 61
11148847 2000
52
A novel gonadotropin-regulated testicular RNA helicase. A new member of the dead-box family. 61
10608860 1999
53
DNA binding affinity of hTRbeta1 mutants as heterodimers with traps from different tissues. 61
10401662 1999
54
Association between an R338L mutation in the thyroid hormone receptor-beta gene and thyrotoxic features in two unrelated kindreds with resistance to thyroid hormone. 61
10037068 1999
55
Selective pituitary resistance to thyroid hormone produced by expression of a mutant thyroid hormone receptor beta gene in the pituitary gland of transgenic mice. 61
9535809 1998
56
Central hyperthyroidism. 61
9534036 1998
57
Clinical and hormonal outcome after two years of triiodothyroacetic acid treatment in a child with thyroid hormone resistance. 61
9349583 1997
58
Resistance to thyroid hormone. 61
9350446 1997
59
Introducing a point mutation identified in a patient with pituitary resistance to thyroid hormone (Arg 338 to Trp) into other mutant thyroid hormone receptors weakens their dominant negative activities. 61
8958790 1996
60
New point mutation (R243W) in the hormone binding domain of the c-erbA beta 1 gene in a family with generalized resistance to thyroid hormone. 61
8664910 1996
61
Thyroid hormone receptor-beta mutants associated with generalized resistance to thyroid hormone show defects in their ligand-sensitive repression function. 61
8584031 1995
62
Functional analysis of a proline to serine mutation in codon 453 of the thyroid hormone receptor beta 1 gene. 61
7593432 1995
63
Functional properties of a mutant T3 receptor beta (R338W) identified in a subject with pituitary resistance to thyroid hormone. 61
8674808 1995
64
Phenotypic variability in patients with generalised resistance to thyroid hormone. 61
7616549 1995
65
Generalized resistance to thyroid hormone: identification of a novel c-erbA beta thyroid hormone receptor variant (Leu450) in a Japanese family and analysis of its secondary structure by the Chou and Fasman method. 61
7873749 1994
66
Genetic analysis of 29 kindreds with generalized and pituitary resistance to thyroid hormone. Identification of thirteen novel mutations in the thyroid hormone receptor beta gene. 61
8040303 1994
67
Resistance to thyroid hormone in children. 61
7951671 1994
68
Hormone-nuclear receptor interactions in health and disease. Thyroid hormone resistance. 61
8092973 1994
69
[Diagnosis of thyroid hormone resistance by molecular biology]. 61
8196182 1994
70
[Resistance to thyroid hormone]. 61
8196181 1994
71
Generalized thyroid hormone resistance due to a deletion of the carboxy terminus of the c-erbA beta receptor. 61
8187964 1994
72
Thyroid function and attention-deficit hyperactivity disorder. 61
8150787 1994
73
Resistance to thyroid hormone and its molecular basis. 61
8165897 1994
74
The variable clinical phenotype in thyroid hormone resistance syndrome. 61
7920008 1994
75
Resistance to thyroid hormone--an uncommon cause of thyroxine excess and inappropriate TSH secretion. 61
7998483 1994
76
Attention-deficit hyperactivity disorder and thyroid function. 61
8410504 1993
77
Thyroid hormone resistance syndrome: correlation of dominant negative activity and location of mutations. 61
8408475 1993
78
Dominant negative inhibition by mutant thyroid hormone receptors is thyroid hormone response element and receptor isoform specific. 61
8264663 1993
79
Identical mutations in unrelated families with generalized resistance to thyroid hormone occur in cytosine-guanine-rich areas of the thyroid hormone receptor beta gene. Analysis of 15 families. 61
8514853 1993
80
Differential expression of mutant and normal beta T3 receptor alleles in kindreds with generalized resistance to thyroid hormone. 61
8486789 1993
81
Thyroid hormone resistance syndromes. 61
8475937 1993
82
Multiple genetic factors in the heterogeneity of thyroid hormone resistance. 61
8421095 1993
83
The relative expression of mutant and normal thyroid hormone receptor genes in patients with generalized resistance to thyroid hormone determined by estimation of their specific messenger ribonucleic acid products. 61
8421105 1993
84
Transcriptional activity of a mutant thyroid hormone receptor beta in a family with generalized resistance to thyroid hormone. 61
1301392 1992
85
Generalized resistance to thyroid hormone (GRTH) in a family: case studies. 61
1294371 1992
86
New insights on the mechanism(s) of the dominant negative effect of mutant thyroid hormone receptor in generalized resistance to thyroid hormone. 61
1430208 1992
87
A point mutation in the 3,5,3'-triiodothyronine-binding domain of thyroid hormone receptor-beta associated with a family with generalized resistance to thyroid hormone. 61
1619012 1992
88
Thyroid hormone receptor mutants that cause resistance to thyroid hormone. Evidence for receptor competition for DNA sequences in target genes. 61
1618799 1992
89
A point mutation of the T3 receptor beta 1 gene in a kindred of generalized resistance to thyroid hormone. 61
1587388 1992
90
Rapid localization of mutations in the thyroid hormone receptor-beta gene by denaturing gradient gel electrophoresis in 18 families with thyroid hormone resistance. 61
1548332 1992
91
Variable transcriptional activity and ligand binding of mutant beta 1 3,5,3'-triiodothyronine receptors from four families with generalized resistance to thyroid hormone. 61
1569968 1992
92
Pituitary resistance to thyroid hormones. 61
1306520 1992
93
Thyroid hormone resistance. 61
1580595 1992
94
Molecular diagnosis and characterization of thyroid hormone resistance syndromes. 61
1668726 1991
95
Neonatal detection of generalized resistance to thyroid hormone. 61
2120481 1990
96
Sex hormone-binding globulin measurement in patients with inappropriate secretion of thyrotropin (IST): evidence against selective pituitary thyroid hormone resistance in nonneoplastic IST. 61
2370293 1990
97
Serum thyrotropin and prolactin in the syndrome of generalized resistance to thyroid hormone: responses to thyrotropin-releasing hormone stimulation and short term triiodothyronine suppression. 61
2110573 1990
98
Syndrome of generalized (peripheral tissue and pituitary) resistance to thyroid hormone. 61
2516399 1989
99
The syndrome of generalized resistance to thyroid hormone (GRTH). 61
2699456 1989
100
Sex hormone-binding globulin in the diagnosis of peripheral tissue resistance to thyroid hormone: the value of changes after short term triiodothyronine administration. 61
3346353 1988
101
Resistance to thyroid hormone diagnosed by the reduced response of fibroblasts to the triiodothyronine-induced suppression of fibronectin synthesis. 61
3597704 1987
102
Hormonal regulation of glycosaminoglycan accumulation in fibroblasts from patients with resistance to thyroid hormone. 61
6630416 1983

Variations for Thyroid Hormone Resistance, Generalized, Autosomal Recessive

ClinVar genetic disease variations for Thyroid Hormone Resistance, Generalized, Autosomal Recessive:

6 (showing 4, show less) ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 THRB THRB, EX4-10DELdeletion Pathogenic 12538
2 THRB NM_001354712.2(THRB):c.1010_1012del (p.Thr337del)deletion Pathogenic 12539 rs387906515 3:24169122-24169124 3:24127631-24127633
3 THRB NM_001354712.2(THRB):c.803C>G (p.Ala268Gly)SNV Pathogenic/Likely pathogenic 492912 rs750905761 3:24174889-24174889 3:24133398-24133398
4 THRB NM_001354712.2(THRB):c.1373T>C (p.Val458Ala)SNV Likely pathogenic 12564 rs121918704 3:24164388-24164388 3:24122897-24122897

Expression for Thyroid Hormone Resistance, Generalized, Autosomal Recessive

Search GEO for disease gene expression data for Thyroid Hormone Resistance, Generalized, Autosomal Recessive.

Pathways for Thyroid Hormone Resistance, Generalized, Autosomal Recessive

GO Terms for Thyroid Hormone Resistance, Generalized, Autosomal Recessive

Sources for Thyroid Hormone Resistance, Generalized, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
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