TDH3
MCID: THY056
MIFTS: 32

Thyroid Dyshormonogenesis 3 (TDH3)

Categories: Endocrine diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Thyroid Dyshormonogenesis 3

MalaCards integrated aliases for Thyroid Dyshormonogenesis 3:

Name: Thyroid Dyshormonogenesis 3 57 12 72 13 70
Tdh3 57 12 72
Hypothyroidism, Congenital, Due to Dyshormonogenesis, 3 57 6
Congenital Hypothyroidism Due to Dyshormonogenesis Type 3 72
Genetic Defect in Thyroid Hormonogenesis Type 3 72
Thyroid Hormonogenesis, Genetic Defect in, 3 57
Genetic Defect in Thyroid Hormonogenesis 3 12
Thyroid Dyshormonogenesis, Type 3 39
Chdh3 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive


HPO:

31
thyroid dyshormonogenesis 3:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0112187
OMIM® 57 274700
MeSH 44 D003409
MedGen 41 C0342194
UMLS 70 C0342194

Summaries for Thyroid Dyshormonogenesis 3

OMIM® : 57 Kanou et al. (2007) reviewed characteristics of thyroid dyshormonogenesis caused by mutations in the thyroglobulin (TG) gene. This form of thyroid dyshormonogenesis has an estimated prevalence of one in 100,000 newborns. Inherited in an autosomal recessive manner, the disorder in the majority of patients causes large goiters of elastic and soft consistency. Although the degree of thyroid dysfunction varies considerably among patients with defective TG synthesis, patients usually have a relatively high serum free T3 concentration with disproportionately low free T4 level. The maintenance of relatively high FT3 levels prevents profound tissue hypothyroidism except in brain and pituitary, which are dependent on T4 supply, resulting in neurologic and intellectual defects in some cases. (274700) (Updated 20-May-2021)

MalaCards based summary : Thyroid Dyshormonogenesis 3, also known as tdh3, is related to thyroid dyshormonogenesis 1 and familial thyroid dyshormonogenesis. An important gene associated with Thyroid Dyshormonogenesis 3 is TG (Thyroglobulin). Affiliated tissues include thyroid and pituitary, and related phenotypes are intellectual disability and goiter

Disease Ontology : 12 A familial thyroid dyshormonogenesis that has material basis in homozygous or compound heterozygous mutation in TG on chromosome 8q24.22.

UniProtKB/Swiss-Prot : 72 Thyroid dyshormonogenesis 3: A disorder due to thyroid dyshormonogenesis, causing large goiters of elastic and soft consistency in the majority of patients. Although the degree of thyroid dysfunction varies considerably among patients with defective thyroglobulin synthesis, patients usually have a relatively high serum free triiodothyronine (T3) concentration with disproportionately low free tetraiodothyronine (T4) level. The maintenance of relatively high free T3 levels prevents profound tissue hypothyroidism except in brain and pituitary, which are dependent on T4 supply, resulting in neurologic and intellectual defects in some cases.

Related Diseases for Thyroid Dyshormonogenesis 3

Diseases in the Thyroid Dyshormonogenesis 2a family:

Thyroid Dyshormonogenesis 1 Thyroid Dyshormonogenesis 3
Thyroid Dyshormonogenesis 4 Thyroid Dyshormonogenesis 5
Thyroid Dyshormonogenesis 6 Familial Thyroid Dyshormonogenesis

Diseases related to Thyroid Dyshormonogenesis 3 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 thyroid dyshormonogenesis 1 10.1
2 familial thyroid dyshormonogenesis 9.5 TG SLA

Symptoms & Phenotypes for Thyroid Dyshormonogenesis 3

Human phenotypes related to Thyroid Dyshormonogenesis 3:

31
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 goiter 31 HP:0000853
3 thyroid carcinoma 31 HP:0002890
4 compensated hypothyroidism 31 HP:0008223
5 increased t3/t4 ratio 31 HP:0012559

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Endocrine Features:
hypothyroidism
euthyroid (compensated hypothyroidism)

Neoplasia:
thyroid cancer

Laboratory Abnormalities:
thyroid hormone coupling defect
excessive iodide trapping
high ft3/ft4 ratio

Head And Neck Neck:
goiter

Neurologic Central Nervous System:
mental retardation (if untreated in infancy)

Clinical features from OMIM®:

274700 (Updated 20-May-2021)

Drugs & Therapeutics for Thyroid Dyshormonogenesis 3

Search Clinical Trials , NIH Clinical Center for Thyroid Dyshormonogenesis 3

Genetic Tests for Thyroid Dyshormonogenesis 3

Anatomical Context for Thyroid Dyshormonogenesis 3

MalaCards organs/tissues related to Thyroid Dyshormonogenesis 3:

40
Thyroid, Pituitary

Publications for Thyroid Dyshormonogenesis 3

Articles related to Thyroid Dyshormonogenesis 3:

(show top 50) (show all 134)
# Title Authors PMID Year
1
Thyroglobulin gene mutations producing defective intracellular transport of thyroglobulin are associated with increased thyroidal type 2 iodothyronine deiodinase activity. 6 57
17244789 2007
2
Haplotype analysis reveals founder effects of thyroglobulin gene mutations C1058R and C1977S in Japan. 6 57
16720658 2006
3
Clinical case seminar: metastatic follicular thyroid carcinoma arising from congenital goiter as a result of a novel splice donor site mutation in the thyroglobulin gene. 57 6
16403815 2006
4
A novel compound heterozygous mutation in the thyroglobulin gene resulting in congenital goitrous hypothyroidism with high serum triiodothyronine levels. 6 57
16477365 2006
5
High incidence of thyroid cancer in long-standing goiters with thyroglobulin mutations. 57 6
16187918 2005
6
Two distinct compound heterozygous constellations (R277X/IVS34-1G>C and R277X/R1511X) in the thyroglobulin (TG) gene in affected individuals of a Brazilian kindred with congenital goiter and defective TG synthesis. 57 6
14764776 2004
7
A 3' splice site mutation in the thyroglobulin gene responsible for congenital goiter with hypothyroidism. 6 57
1752952 1991
8
Low levels of thyroglobulin messenger ribonucleic acid in congenital goitrous hypothyroidism with defective thyroglobulin synthesis. 57 6
2584351 1989
9
Phenotype risk scores identify patients with unrecognized Mendelian disease patterns. 6
29590070 2018
10
Against all odds: blended phenotypes of three single-gene defects. 6
26813946 2016
11
New insights into thyroglobulin gene: molecular analysis of seven novel mutations associated with goiter and hypothyroidism. 6
23164529 2013
12
A new compound heterozygous for c.886C>T/c.2206C>T [p.R277X/p.Q717X] mutations in the thyroglobulin gene as a cause of foetal goitrous hypothyroidism. 6
21128992 2011
13
New insights into thyroglobulin pathophysiology revealed by the study of a family with congenital goiter. 6
20410234 2010
14
Human Splicing Finder: an online bioinformatics tool to predict splicing signals. 6
19339519 2009
15
Naturally occurring mutations in the thyroglobulin gene. 57
16187910 2005
16
A new case of congenital goiter with hypothyroidism caused by a homozygous p.R277X mutation in the exon 7 of the thyroglobulin gene: a mutational hot spot could explain the recurrence of this mutation. 6
15769978 2005
17
Compound heterozygous mutations in the thyroglobulin gene (1143delC and 6725G-->A [R2223H]) resulting in fetal goitrous hypothyroidism. 6
12915634 2003
18
Congenital goiter with hypothyroidism caused by a 5' splice site mutation in the thyroglobulin gene. 6
11484898 2001
19
A premature stopcodon in thyroglobulin messenger RNA results in familial goiter and moderate hypothyroidism. 6
10404833 1999
20
Two novel cysteine substitutions (C1263R and C1995S) of thyroglobulin cause a defect in intracellular transport of thyroglobulin in patients with congenital goiter and the variant type of adenomatous goiter. 6
10199792 1999
21
Evidence for the segregation of three different mutated alleles of the thyroglobulin gene in a Brazilian family with congenital goiter and hypothyroidism. 6
9588493 1998
22
Prenatal diagnosis and treatment of dyshormonogenetic fetal goiter due to defective thyroglobulin synthesis. 57
9398747 1997
23
A variant of adenomatous goiter with characteristic histology and possible hereditary thyroglobulin abnormality. 57
8626865 1996
24
A 138-nucleotide deletion in the thyroglobulin ribonucleic acid messenger in a congenital goiter with defective thyroglobulin synthesis. 6
7593451 1995
25
A nonsense mutation causes human hereditary congenital goiter with preferential production of a 171-nucleotide-deleted thyroglobulin ribonucleic acid messenger. 6
8325944 1993
26
Merging autosomal dominance and recessivity. 57
3661566 1987
27
Unusual scarcity of restriction site polymorphism in the human thyroglobulin gene. A linkage study suggesting autosomal dominance of a defective thyroglobulin allele. 57
6088387 1984
28
Inherited disorders of thyroid metabolism. 57
6354701 1983
29
Congenital goiter and the development of metastatic follicular carcinoma with evidence for a leak of nonhormonal iodide: clinical, pathological, kinetic, and biochemical studies and a review of the literature. 57
7462393 1981
30
Abnormal cellular localization of thyroglobulin mRNA associated with hereditary congenital goiter and thyroglobulin deficiency. 57
272675 1978
31
Defective thyroglobulin export as a cause of congenital goitre. 57
1157342 1975
32
A goitrous subject with structural abnormality of thyroglobulin. 57
4628864 1972
33
Studies on the congenitally goitrous sheep. Iodoproteins of the goitre. 57
5419739 1970
34
Congenital goiter with hypothyroidism and iodo-serum albumin replacing thyroglobulin. 57
4163612 1967
35
THYROIDAL IODOPROTEINS IN PATIENTS WITH GOITROUS HYPOTHYROIDISM. 57
14167076 1964
36
Differential Roles of a Family of Flavodoxin-Like Proteins That Promote Resistance to Quinone-Mediated Oxidative Stress in Candida albicans. 61
33468576 2021
37
Construction of lactic acid-tolerant Saccharomyces cerevisiae by using CRISPR-Cas-mediated genome evolution for efficient D-lactic acid production. 61
32960291 2020
38
Aberrant Intracellular pH Regulation Limiting Glyceraldehyde-3-Phosphate Dehydrogenase Activity in the Glucose-Sensitive Yeast tps1Δ Mutant. 61
33109759 2020
39
Promoter-Library-Based Pathway Optimization for Efficient (2S)-Naringenin Production from p-Coumaric Acid in Saccharomyces cerevisiae. 61
32458684 2020
40
The formation of hybrid complexes between isoenzymes of glyceraldehyde-3-phosphate dehydrogenase regulates its aggregation state, the glycolytic activity and sphingolipid status in Saccharomyces cerevisiae. 61
31743950 2020
41
Combining proteomics and lipid analysis to unravel Confidor stress response in Saccharomyces cerevisiae. 61
31696623 2020
42
Compensatory trans-regulatory alleles minimizing variation in TDH3 expression are common within Saccharomyces cerevisiae. 61
31636938 2019
43
Moonlighting proteins are variably exposed at the cell surfaces of Candida glabrata, Candida parapsilosis and Candida tropicalis under certain growth conditions. 61
31269895 2019
44
YHp as a highly stable, hyper-copy, hyper-expression plasmid constructed using a full 2-μm circle sequence in cir0 strains of Saccharomyces cerevisiae. 61
30537227 2019
45
Tunable Expression Systems for Orthogonal DNA Replication. 61
30408954 2018
46
Clioquinol induces G2/M cell cycle arrest through the up-regulation of TDH3 in Saccharomyces cerevisiae. 61
30031471 2018
47
Fitness effects of altering gene expression noise in Saccharomyces cerevisiae. 61
30124429 2018
48
The external face of Candida albicans: A proteomic view of the cell surface and the extracellular environment. 61
29223801 2018
49
Condition-specific promoter activities in Saccharomyces cerevisiae. 61
29631591 2018
50
The HMGB protein Ixr1 interacts with Ssn8 and Tdh3 involved in transcriptional regulation. 61
29438513 2018

Variations for Thyroid Dyshormonogenesis 3

ClinVar genetic disease variations for Thyroid Dyshormonogenesis 3:

6 (show top 50) (show all 296)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TG NM_003235.5(TG):c.7021G>A (p.Gly2341Ser) SNV Pathogenic 545609 rs898275076 GRCh37: 8:134034380-134034380
GRCh38: 8:133022135-133022135
2 TG TG, 138-BP DEL, NT5590 TG, IVS30, +1, G-T Deletion Pathogenic 12692 GRCh37:
GRCh38:
3 TG NM_003235.5(TG):c.3229T>C (p.Cys1077Arg) SNV Pathogenic 12702 rs137854433 GRCh37: 8:133911054-133911054
GRCh38: 8:132898809-132898809
4 TG NM_003235.5(TG):c.7123G>A (p.Gly2375Arg) SNV Pathogenic 12703 rs137854434 GRCh37: 8:134042152-134042152
GRCh38: 8:133029907-133029907
5 TG NM_003235.5(TG):c.5690G>A (p.Cys1897Tyr) SNV Pathogenic 12704 rs121912649 GRCh37: 8:133980042-133980042
GRCh38: 8:132967797-132967797
6 TG NM_003235.5(TG):c.48G>A (p.Trp16Ter) SNV Pathogenic 915466 GRCh37: 8:133879293-133879293
GRCh38: 8:132867048-132867048
7 TG NM_003235.5(TG):c.275-3C>G SNV Pathogenic 12689 rs1587166863 GRCh37: 8:133883590-133883590
GRCh38: 8:132871345-132871345
8 TG NM_003235.5(TG):c.1143del (p.Tyr382fs) Deletion Pathogenic 12699 rs778849740 GRCh37: 8:133898760-133898760
GRCh38: 8:132886515-132886515
9 TG NM_003235.5(TG):c.6200-1G>C SNV Pathogenic 12701 rs1587678058 GRCh37: 8:133995594-133995594
GRCh38: 8:132983349-132983349
10 TG NM_003235.5(TG):c.3733T>C (p.Cys1245Arg) SNV Pathogenic 12693 rs121912647 GRCh37: 8:133919031-133919031
GRCh38: 8:132906786-132906786
11 TG NM_003235.5(TG):c.5986T>A (p.Cys1996Ser) SNV Pathogenic 12694 rs2076739 GRCh37: 8:133984049-133984049
GRCh38: 8:132971804-132971804
12 TG NM_003235.5(TG):c.7007G>A (p.Arg2336Gln) SNV Pathogenic 12705 rs121912650 GRCh37: 8:134034366-134034366
GRCh38: 8:133022121-133022121
13 TG NM_003235.5(TG):c.5184C>A (p.Cys1728Ter) SNV Pathogenic 208619 rs199599591 GRCh37: 8:133953738-133953738
GRCh38: 8:132941493-132941493
14 TG NM_003235.5(TG):c.266dup (p.Val90fs) Duplication Pathogenic 436997 rs1554649344 GRCh37: 8:133882061-133882062
GRCh38: 8:132869816-132869817
15 TG NM_003235.5(TG):c.475C>T (p.Arg159Ter) SNV Pathogenic 1028100 GRCh37: 8:133883793-133883793
GRCh38: 8:132871548-132871548
16 TG NM_003235.5(TG):c.8055G>A (p.Trp2685Ter) SNV Pathogenic 1028102 GRCh37: 8:134145771-134145771
GRCh38: 8:133133527-133133527
17 TG NM_003235.5(TG):c.1351C>T (p.Arg451Ter) SNV Pathogenic 1031314 GRCh37: 8:133898968-133898968
GRCh38: 8:132886723-132886723
18 TG NM_003235.5(TG):c.4588C>T (p.Arg1530Ter) SNV Pathogenic 12691 rs121912646 GRCh37: 8:133935642-133935642
GRCh38: 8:132923397-132923397
19 TG NM_003235.5(TG):c.886C>T (p.Arg296Ter) SNV Pathogenic 12695 rs121912648 GRCh37: 8:133894854-133894854
GRCh38: 8:132882609-132882609
20 TG NM_003235.5(TG):c.638+1G>A SNV Pathogenic 12706 rs1587178555 GRCh37: 8:133885467-133885467
GRCh38: 8:132873222-132873222
21 TG NM_003235.5(TG):c.3329_3330+1dup Duplication Pathogenic 1031316 GRCh37: 8:133911151-133911152
GRCh38: 8:132898906-132898907
22 TG NM_003235.5(TG):c.416G>A (p.Trp139Ter) SNV Pathogenic 1031317 GRCh37: 8:133883734-133883734
GRCh38: 8:132871489-132871489
23 TG NM_003235.5(TG):c.4378+1G>T SNV Pathogenic 1031318 GRCh37: 8:133925511-133925511
GRCh38: 8:132913266-132913266
24 SLA , TG NM_003235.5(TG):c.7502G>A (p.Trp2501Ter) SNV Pathogenic 1031319 GRCh37: 8:134108547-134108547
GRCh38: 8:133096303-133096303
25 TG NM_003235.5(TG):c.8210C>A (p.Ser2737Ter) SNV Pathogenic 1031321 GRCh37: 8:134146941-134146941
GRCh38: 8:133134697-133134697
26 TG NM_003235.5(TG):c.6725G>A (p.Arg2242His) SNV Pathogenic/Likely pathogenic 12700 rs2069566 GRCh37: 8:134030185-134030185
GRCh38: 8:133017940-133017940
27 TG NM_003235.5(TG):c.6791G>A (p.Cys2264Tyr) SNV Likely pathogenic 917855 GRCh37: 8:134031855-134031855
GRCh38: 8:133019610-133019610
28 TG NM_003235.5(TG):c.229G>A (p.Gly77Ser) SNV Conflicting interpretations of pathogenicity 436996 rs142698837 GRCh37: 8:133882026-133882026
GRCh38: 8:132869781-132869781
29 TG NM_003235.5(TG):c.8205del (p.Gln2736fs) Deletion Conflicting interpretations of pathogenicity 632023 rs758002273 GRCh37: 8:134146934-134146934
GRCh38: 8:133134690-133134690
30 TG NM_003235.5(TG):c.2359C>T (p.Arg787Ter) SNV Conflicting interpretations of pathogenicity 632071 rs752966476 GRCh37: 8:133900411-133900411
GRCh38: 8:132888166-132888166
31 TG NM_003235.5(TG):c.638+5G>A SNV Conflicting interpretations of pathogenicity 218239 rs774274702 GRCh37: 8:133885471-133885471
GRCh38: 8:132873226-132873226
32 TG NM_003235.5(TG):c.5386C>T (p.Gln1796Ter) SNV Uncertain significance 361975 rs754658907 GRCh37: 8:133961173-133961173
GRCh38: 8:132948928-132948928
33 TG NM_003235.5(TG):c.2761+2T>G SNV Uncertain significance 361930 rs886062705 GRCh37: 8:133900815-133900815
GRCh38: 8:132888570-132888570
34 TG NM_003235.5(TG):c.2455C>T (p.Leu819Phe) SNV Uncertain significance 361925 rs886062704 GRCh37: 8:133900507-133900507
GRCh38: 8:132888262-132888262
35 TG NM_003235.5(TG):c.4982G>A (p.Arg1661His) SNV Uncertain significance 361968 rs115509019 GRCh37: 8:133948050-133948050
GRCh38: 8:132935805-132935805
36 TG NM_003235.5(TG):c.1532A>G (p.Asn511Ser) SNV Uncertain significance 361914 rs192077055 GRCh37: 8:133899149-133899149
GRCh38: 8:132886904-132886904
37 TG NM_003235.5(TG):c.2709G>C (p.Glu903Asp) SNV Uncertain significance 361928 rs755672784 GRCh37: 8:133900761-133900761
GRCh38: 8:132888516-132888516
38 TG NM_003235.5(TG):c.8189-14C>T SNV Uncertain significance 362004 rs374177941 GRCh37: 8:134146906-134146906
GRCh38: 8:133134662-133134662
39 TG NM_003235.5(TG):c.1963C>T (p.Gln655Ter) SNV Uncertain significance 632020 rs771807370 GRCh37: 8:133899580-133899580
GRCh38: 8:132887335-132887335
40 TG NM_003235.5(TG):c.5895C>A (p.Tyr1965Ter) SNV Uncertain significance 632021 rs1255388549 GRCh37: 8:133981734-133981734
GRCh38: 8:132969489-132969489
41 TG NM_003235.5(TG):c.1333C>T (p.Arg445Ter) SNV Uncertain significance 632515 rs748309986 GRCh37: 8:133898950-133898950
GRCh38: 8:132886705-132886705
42 SLA , TG NM_003235.5(TG):c.7539C>T (p.Asp2513=) SNV Uncertain significance 361994 rs114539802 GRCh37: 8:134108584-134108584
GRCh38: 8:133096340-133096340
43 TG NM_003235.5(TG):c.5856G>A (p.Arg1952=) SNV Uncertain significance 361978 rs115476696 GRCh37: 8:133980208-133980208
GRCh38: 8:132967963-132967963
44 TG NM_003235.5(TG):c.198C>T (p.Asp66=) SNV Uncertain significance 361907 rs141082783 GRCh37: 8:133881995-133881995
GRCh38: 8:132869750-132869750
45 TG NM_003235.5(TG):c.2150G>A (p.Arg717Gln) SNV Uncertain significance 361921 rs200611812 GRCh37: 8:133899767-133899767
GRCh38: 8:132887522-132887522
46 TG NM_003235.5(TG):c.4379-13T>G SNV Uncertain significance 361960 rs886062708 GRCh37: 8:133931608-133931608
GRCh38: 8:132919363-132919363
47 TG NM_003235.5(TG):c.7648G>A (p.Glu2550Lys) SNV Uncertain significance 361999 rs199724462 GRCh37: 8:134125741-134125741
GRCh38: 8:133113497-133113497
48 TG NM_003235.5(TG):c.3241C>G (p.Arg1081Gly) SNV Uncertain significance 361944 rs745902921 GRCh37: 8:133911066-133911066
GRCh38: 8:132898821-132898821
49 TG NM_003235.5(TG):c.2330C>T (p.Pro777Leu) SNV Uncertain significance 361923 rs3739274 GRCh37: 8:133900382-133900382
GRCh38: 8:132888137-132888137
50 TG NM_003235.5(TG):c.6945G>A (p.Pro2315=) SNV Uncertain significance 361988 rs769872031 GRCh37: 8:134034304-134034304
GRCh38: 8:133022059-133022059

UniProtKB/Swiss-Prot genetic disease variations for Thyroid Dyshormonogenesis 3:

72
# Symbol AA change Variation ID SNP ID
1 TG p.Cys1264Arg VAR_010216 rs2076738
2 TG p.Cys1996Ser VAR_010219 rs2076739
3 TG p.Cys183Tyr VAR_063034
4 TG p.Cys1897Tyr VAR_063035 rs121912649
5 TG p.Ala2234Asp VAR_063036 rs370991693
6 TG p.Arg2336Gln VAR_063037 rs121912650
7 TG p.Gly2375Arg VAR_063038 rs137854434

Expression for Thyroid Dyshormonogenesis 3

Search GEO for disease gene expression data for Thyroid Dyshormonogenesis 3.

Pathways for Thyroid Dyshormonogenesis 3

GO Terms for Thyroid Dyshormonogenesis 3

Sources for Thyroid Dyshormonogenesis 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
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32 ICD10
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57 OMIM® (Updated 20-May-2021)
61 PubMed
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