TDH2A
MCID: THY061
MIFTS: 30

Thyroid Dyshormonogenesis 2a (TDH2A)

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

Aliases & Classifications for Thyroid Dyshormonogenesis 2a

MalaCards integrated aliases for Thyroid Dyshormonogenesis 2a:

Name: Thyroid Dyshormonogenesis 2a 57 12 72 13
Deficiency of Iodide Peroxidase 29 6 70
Iodide Peroxidase Deficiency 57 12 72
Tdh2a 57 12 72
Genetic Defect in Thyroid Hormonogenesis 2a 12 72
Thyroid Peroxidase Deficiency 57 12
Congenital Hypothyroidism Due to Dyshormonogenesis Type 2a 72
Hypothyroidism, Congenital, Due to Dyshormonogenesis, 2a 57
Thyroid Hormonogenesis, Genetic Defect in, 2a 57
Thyroid Hormone Organification Defect 2 72
Chdh2a 72
Tiod 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
thyroid dyshormonogenesis 2a:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0112186
OMIM® 57 274500
MeSH 44 D003409
MedGen 41 C1291299
SNOMED-CT via HPO 68 258211005 3716002 40930008
UMLS 70 C1291299

Summaries for Thyroid Dyshormonogenesis 2a

OMIM® : 57 Approximately 10% of patients with congenital hypothyroidism harbor inborn errors of metabolism in one of the steps for thyroid hormone synthesis in thyrocytes (Vono-Toniolo et al., 2005). The most prevalent cause of thyroid dyshormonogenesis is TPO deficiency (Park and Chatterjee, 2005). Defects in TPO cause a severe form of congenital hypothyroidism characterized by a complete and immediate release of accumulated radioiodide from the thyroid after sodium perchlorate administration (Bakker et al., 2000). This release of radioiodide represents total iodine organification defect (TIOD), a disruption of the process by which iodide present in the thyroid is oxidized by hydrogen peroxide and bound to tyrosine residues in thyroglobulin (TG; 188450) to form iodotyrosine. (274500) (Updated 05-Apr-2021)

MalaCards based summary : Thyroid Dyshormonogenesis 2a, also known as deficiency of iodide peroxidase, is related to hypothyroidism and congenital hypothyroidism. An important gene associated with Thyroid Dyshormonogenesis 2a is TPO (Thyroid Peroxidase). Affiliated tissues include thyroid, and related phenotypes are hypothyroidism and goiter

Disease Ontology : 12 A familial thyroid dyshormonogenesis that has material basis in homozygous or compound heterozygous mutation in TPO on chromosome 2p25.3.

UniProtKB/Swiss-Prot : 72 Thyroid dyshormonogenesis 2A: A disorder due to defective conversion of accumulated iodide to organically bound iodine. The iodide organification defect can be partial or complete.

Related Diseases for Thyroid Dyshormonogenesis 2a

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 2a via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hypothyroidism 10.1
2 congenital hypothyroidism 9.9
3 goiter 9.9

Symptoms & Phenotypes for Thyroid Dyshormonogenesis 2a

Human phenotypes related to Thyroid Dyshormonogenesis 2a:

31
# Description HPO Frequency HPO Source Accession
1 hypothyroidism 31 HP:0000821
2 goiter 31 HP:0000853
3 abnormality of metabolism/homeostasis 31 HP:0001939
4 thyroid defect in oxidation and organification of iodide 31 HP:0008263

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Endocrine Features:
hypothyroidism
thyroid defect in oxidation and organification of iodide

Laboratory Abnormalities:
rapid radioactive iodide (rai) discharge after thiocyanate or perchlorate
thyroid peroxidase defect
tyrosine iodination defect

Head And Neck Neck:
goiter

Clinical features from OMIM®:

274500 (Updated 05-Apr-2021)

Drugs & Therapeutics for Thyroid Dyshormonogenesis 2a

Search Clinical Trials , NIH Clinical Center for Thyroid Dyshormonogenesis 2a

Genetic Tests for Thyroid Dyshormonogenesis 2a

Genetic tests related to Thyroid Dyshormonogenesis 2a:

# Genetic test Affiliating Genes
1 Deficiency of Iodide Peroxidase 29 TPO

Anatomical Context for Thyroid Dyshormonogenesis 2a

MalaCards organs/tissues related to Thyroid Dyshormonogenesis 2a:

40
Thyroid

Publications for Thyroid Dyshormonogenesis 2a

Articles related to Thyroid Dyshormonogenesis 2a:

(show all 48)
# Title Authors PMID Year
1
Two decades of screening for congenital hypothyroidism in The Netherlands: TPO gene mutations in total iodide organification defects (an update). 57 6
11061528 2000
2
Two different mutations in the thyroid peroxidase gene of a large inbred Amish kindred: power and limits of homozygosity mapping. 57 6
10084596 1999
3
Metastatic thyroid carcinoma arising from congenital goiter due to mutation in the thyroperoxidase gene. 57 6
9814507 1998
4
Congenital hypothyroidism caused by a premature termination signal in exon 10 of the human thyroid peroxidase gene. 6 57
8964831 1996
5
Identification of five novel inactivating mutations in the human thyroid peroxidase gene by denaturing gradient gel electrophoresis. 6 57
7550241 1995
6
A 20-basepair duplication in the human thyroid peroxidase gene results in a total iodide organification defect and congenital hypothyroidism. 57 6
8027236 1994
7
Identification of a mutation in the coding sequence of the human thyroid peroxidase gene causing congenital goiter. 6 57
1401057 1992
8
High frequency of mutations in 'dyshormonogenesis genes' in severe congenital hypothyroidism. 6
30240412 2018
9
Detection of Novel Gene Variants Associated with Congenital Hypothyroidism in a Finnish Patient Cohort. 6
27373559 2016
10
A Homozygous TPO Gene Duplication (c.1184_1187dup4) Causes Congenital Hypothyroidism in Three Siblings Born to a Consanguineous Family. 6
27617131 2015
11
One Base Deletion (c.2422delT) in the TPO Gene Causes Severe Congenital Hypothyroidism. 6
25241611 2014
12
Detection of heterozygous c.1708C>T and c.1978C>G thyroid peroxidase (TPO) mutations in Iraqi patients with toxic and nontoxic goiter. 6
24482635 2014
13
Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community. 6
23236987 2013
14
Congenital goitrous primary hypothyroidism in two German families caused by novel thyroid peroxidase (TPO) gene mutations. 6
23512414 2013
15
Pseudodominant inheritance of goitrous congenital hypothyroidism caused by TPO mutations: molecular and in silico studies. 6
18029453 2008
16
Clinical description of infants with congenital hypothyroidism and iodide organification defects. 57
18772598 2008
17
High prevalence of thyroid peroxidase gene mutations in patients with thyroid dyshormonogenesis. 6
17468186 2007
18
Naturally occurring mutations in the thyroglobulin gene. 57
16187910 2005
19
Genetics of congenital hypothyroidism. 57
15863666 2005
20
Mutation screening of the thyroid peroxidase gene in a cohort of 55 Portuguese patients with congenital hypothyroidism. 6
15745925 2005
21
Thyroperoxidase gene mutations in congenital goitrous hypothyroidism with total and partial iodide organification defect. 6
14751036 2003
22
Monoallelic expression of mutant thyroid peroxidase allele causing total iodide organification defect. 6
12843174 2003
23
High prevalence of a novel mutation (2268 insT) of the thyroid peroxidase gene in Taiwanese patients with total iodide organification defect, and evidence for a founder effect. 6
12213873 2002
24
Two novel missense mutations in the thyroid peroxidase gene, R665W and G771R, result in a localization defect and cause congenital hypothyroidism. 6
11916616 2002
25
Maternal isodisomy for chromosome 2p causing severe congenital hypothyroidism. 6
11238503 2001
26
A novel mutation in the TPO gene in goitrous hypothyroid patients with iodide organification defect. 6
10468986 1999
27
Molecular analysis of mutated thyroid peroxidase detected in patients with total iodide organification defects. 6
9024270 1997
28
Tetranucleotide repeat polymorphism at the human thyroid peroxidase (hTPO) locus. 57
1339470 1992
29
Genetic linkage studies of thyroid peroxidase (TPO) gene in families with TPO deficiency. 57
1671388 1991
30
Congenital hypothyroidism caused by defective iodide transport. 57
3998954 1985
31
Congenital goiter with defective iodide transport. 57
6313338 1983
32
Familial thyroid peroxidase defect. 57
7116652 1982
33
Partial and total iodide organification defect in different sibships in a kindred. 57
192074 1977
34
Thyroid iodine organification defects: a case with lack of thyroglobulin iodination and a case without any peroxidase activity. 57
1262432 1976
35
Differentiation of two abnormalities in thyroid peroxidase causing organification defect and goitrous hypothyroidism. 57
162974 1975
36
A defective thyroid peroxidase solubilized from a familial goiter with iodine organification defect. 57
4835124 1974
37
Peroxidase defect in congenital goiter with complete organification block. 57
4345693 1973
38
Peroxidase deficiency in familial goiter with iodide organification defect. 57
4330593 1971
39
Thyroxine biosynthesis in human goitrous cretinism. 57
4189569 1970
40
DEFECTIVE COUPLING OF IODOTYROSINE IN FAMILIAL GOITERS; REPORT OF TWO PATIENTS. 57
14170622 1964
41
GENETIC STUDIES IN FAMILIAL GOITROUS CRETINISM. 57
14175495 1964
42
Inheritance of defective organification of iodine in familial goitrous cretinism. 57
13732855 1961
43
Defect of the iodinating system in congenital goitrous cretinism: report of a case with biochemical studies. 57
13830735 1959
44
Mild thyroid peroxidase deficiency caused by TPO mutations with residual activity: Correlation between clinical phenotypes and enzymatic activity. 61
28867693 2017
45
Novel human pathological mutations. Gene symbol: TPO. Disease: Thyroid peroxidase deficiency. 61
20108397 2010
46
Thyroid dyshormonogenesis. 61
16424561 2005
47
Congenital hypothyroidism with goiter in toy fox terriers. 61
12564727 2003
48
Thyroid peroxidase deficiency in Batten-Spielmeyer-Vogt disease. 61
167705 1975

Variations for Thyroid Dyshormonogenesis 2a

ClinVar genetic disease variations for Thyroid Dyshormonogenesis 2a:

6 (show top 50) (show all 136)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TPO TPO, 4-BP INS, NT1227 Insertion Pathogenic 4040 GRCh37:
GRCh38:
2 TPO TPO, 20-BP DUP Duplication Pathogenic 4041 GRCh37:
GRCh38:
3 TPO NM_001206744.2(TPO):c.1339A>T (p.Ile447Phe) SNV Pathogenic 4043 rs104893669 GRCh37: 2:1488368-1488368
GRCh38: 2:1484596-1484596
4 TPO NM_001206744.2(TPO):c.1768G>A (p.Gly590Ser) SNV Pathogenic 4045 rs121908084 GRCh37: 2:1491763-1491763
GRCh38: 2:1487991-1487991
5 TPO TPO, 1-BP INS, 2505C Insertion Pathogenic 4047 GRCh37:
GRCh38:
6 TPO NM_001206744.2(TPO):c.1943G>A (p.Arg648Gln) SNV Pathogenic 4048 rs121908086 GRCh37: 2:1497748-1497748
GRCh38: 2:1493976-1493976
7 TPO NM_001206744.2(TPO):c.2077C>T (p.Arg693Trp) SNV Pathogenic 4051 rs121908087 GRCh37: 2:1499831-1499831
GRCh38: 2:1496059-1496059
8 TPO NM_001206744.2(TPO):c.1496del (p.Pro499fs) Deletion Pathogenic 4052 rs1573380429 GRCh37: 2:1488523-1488523
GRCh38: 2:1484751-1484751
9 TPO NM_001206744.2(TPO):c.1994G>A (p.Arg665Gln) SNV Pathogenic 374344 rs140124953 GRCh37: 2:1497799-1497799
GRCh38: 2:1494027-1494027
10 TPO NM_001206744.2(TPO):c.2395G>A (p.Glu799Lys) SNV Pathogenic 4046 rs121908085 GRCh37: 2:1507728-1507728
GRCh38: 2:1503956-1503956
11 TPO NM_001206744.2(TPO):c.2512del (p.Cys838fs) Deletion Pathogenic 4049 rs1573459560 GRCh37: 2:1507845-1507845
GRCh38: 2:1504073-1504073
12 TPO NM_001206744.2(TPO):c.2421del (p.Cys808fs) Deletion Pathogenic 623380 rs760307139 GRCh37: 2:1507748-1507748
GRCh38: 2:1503976-1503976
13 TPO NM_001206744.2(TPO):c.764dup (p.Gly256fs) Duplication Pathogenic 623381 rs1558307375 GRCh37: 2:1459994-1459995
GRCh38: 2:1456222-1456223
14 TPO NM_001206744.2(TPO):c.1618C>T (p.Arg540Ter) SNV Pathogenic 4042 rs121908082 GRCh37: 2:1491613-1491613
GRCh38: 2:1487841-1487841
15 TPO NM_001206744.2(TPO):c.1357T>G (p.Tyr453Asp) SNV Pathogenic 4044 rs121908083 GRCh37: 2:1488386-1488386
GRCh38: 2:1484614-1484614
16 TPO NM_001206744.2(TPO):c.1978C>G (p.Gln660Glu) SNV Pathogenic 4053 rs121908088 GRCh37: 2:1497783-1497783
GRCh38: 2:1494011-1494011
17 TPO NM_001206744.2(TPO):c.1955dup (p.Phe653fs) Duplication Pathogenic 4054 rs1491142370 GRCh37: 2:1497759-1497760
GRCh38: 2:1493987-1493988
18 TPO NM_001206744.2(TPO):c.2422del (p.Cys808fs) Deletion Pathogenic 632332 rs763662774 GRCh37: 2:1507755-1507755
GRCh38: 2:1503983-1503983
19 TPO NM_001206744.2(TPO):c.1184_1187dup (p.Ala397fs) Duplication Pathogenic 429301 rs763941231 GRCh37: 2:1481219-1481220
GRCh38: 2:1477447-1477448
20 TPO NM_001206744.2(TPO):c.2268dup (p.Glu757Ter) Duplication Pathogenic 4050 rs770781635 GRCh37: 2:1500418-1500419
GRCh38: 2:1496646-1496647
21 TPO NM_001206744.2(TPO):c.214C>T (p.Gln72Ter) SNV Pathogenic 1028337 GRCh37: 2:1437244-1437244
GRCh38: 2:1433472-1433472
22 TPO NM_001206744.2(TPO):c.1558C>T (p.His520Tyr) SNV Likely pathogenic 374178 rs1057518950 GRCh37: 2:1488587-1488587
GRCh38: 2:1484815-1484815
23 TPO NM_001206744.2(TPO):c.719A>G (p.Asp240Gly) SNV Likely pathogenic 869101 GRCh37: 2:1459954-1459954
GRCh38: 2:1456182-1456182
24 TPO NM_001206744.2(TPO):c.2315A>G (p.Tyr772Cys) SNV Likely pathogenic 916543 GRCh37: 2:1500466-1500466
GRCh38: 2:1496694-1496694
25 TPO NM_001206744.2(TPO):c.1430_1450del (p.Ala477_Asn483del) Deletion Uncertain significance 930340 GRCh37: 2:1488457-1488477
GRCh38: 2:1484685-1484705
26 TPO NM_001206744.2(TPO):c.1747G>T (p.Gly583Cys) SNV Uncertain significance 931713 GRCh37: 2:1491742-1491742
GRCh38: 2:1487970-1487970
27 TPO NM_001206744.2(TPO):c.2242G>A (p.Val748Met) SNV Uncertain significance 256612 rs28991292 GRCh37: 2:1500393-1500393
GRCh38: 2:1496621-1496621
28 TPO NM_001206744.2(TPO):c.660C>T (p.Val220=) SNV Uncertain significance 256615 rs151154074 GRCh37: 2:1459895-1459895
GRCh38: 2:1456123-1456123
29 TPO NM_001206744.2(TPO):c.1312C>T (p.Arg438Cys) SNV Uncertain significance 1028336 GRCh37: 2:1481350-1481350
GRCh38: 2:1477578-1477578
30 TPO NM_001206744.2(TPO):c.9G>A (p.Ala3=) SNV Uncertain significance 331217 rs61758084 GRCh37: 2:1418189-1418189
GRCh38: 2:1414417-1414417
31 TPO NM_001206744.2(TPO):c.1857C>G (p.Ala619=) SNV Uncertain significance 331358 rs140322336 GRCh37: 2:1497662-1497662
GRCh38: 2:1493890-1493890
32 TPO NM_001206744.2(TPO):c.2488G>A (p.Glu830Lys) SNV Uncertain significance 74130 rs145974595 GRCh37: 2:1507821-1507821
GRCh38: 2:1504049-1504049
33 TPO NM_001206744.2(TPO):c.1294G>A (p.Ala432Thr) SNV Uncertain significance 331316 rs886054900 GRCh37: 2:1481332-1481332
GRCh38: 2:1477560-1477560
34 TPO NM_001206744.2(TPO):c.2181G>T (p.Met727Ile) SNV Uncertain significance 331364 rs886054919 GRCh37: 2:1499935-1499935
GRCh38: 2:1496163-1496163
35 TPO NM_001206744.2(TPO):c.2241C>T (p.Ser747=) SNV Uncertain significance 331367 rs373350060 GRCh37: 2:1500392-1500392
GRCh38: 2:1496620-1496620
36 TPO NM_001206744.2(TPO):c.12C>T (p.Leu4=) SNV Uncertain significance 331218 rs9678281 GRCh37: 2:1418192-1418192
GRCh38: 2:1414420-1414420
37 TPO NM_001206744.2(TPO):c.95-4G>A SNV Uncertain significance 331221 rs757494249 GRCh37: 2:1426813-1426813
GRCh38: 2:1423041-1423041
38 TPO NM_001206744.2(TPO):c.-2+19T>C SNV Uncertain significance 331216 rs886054871 GRCh37: 2:1417336-1417336
GRCh38: 2:1413564-1413564
39 TPO NM_001206744.2(TPO):c.612G>A (p.Pro204=) SNV Uncertain significance 331308 rs3732349 GRCh37: 2:1457595-1457595
GRCh38: 2:1453823-1453823
40 TPO NM_001206744.2(TPO):c.443C>T (p.Ala148Val) SNV Uncertain significance 331224 rs138509145 GRCh37: 2:1440117-1440117
GRCh38: 2:1436345-1436345
41 TPO NM_001206744.2(TPO):c.759C>T (p.Phe253=) SNV Uncertain significance 331311 rs757051221 GRCh37: 2:1459994-1459994
GRCh38: 2:1456222-1456222
42 TPO NM_001206744.2(TPO):c.2436G>A (p.Ala812=) SNV Uncertain significance 331392 rs763673114 GRCh37: 2:1507769-1507769
GRCh38: 2:1503997-1503997
43 TPO NM_001206744.2(TPO):c.2717C>T (p.Pro906Leu) SNV Uncertain significance 331640 rs138289170 GRCh37: 2:1544464-1544464
GRCh38: 2:1540692-1540692
44 TPO NM_001206744.2(TPO):c.840G>A (p.Pro280=) SNV Uncertain significance 331313 rs187974063 GRCh37: 2:1480878-1480878
GRCh38: 2:1477106-1477106
45 TPO NM_001206744.2(TPO):c.1899T>C (p.Asp633=) SNV Uncertain significance 331359 rs199621917 GRCh37: 2:1497704-1497704
GRCh38: 2:1493932-1493932
46 TPO NM_001206744.2(TPO):c.2647C>T (p.Pro883Ser) SNV Uncertain significance 225496 rs190968346 GRCh37: 2:1544394-1544394
GRCh38: 2:1540622-1540622
47 TPO NM_001206744.2(TPO):c.2299T>C (p.Ser767Pro) SNV Uncertain significance 1028338 GRCh37: 2:1500450-1500450
GRCh38: 2:1496678-1496678
48 TPO NM_001206744.2(TPO):c.*124G>C SNV Uncertain significance 331646 rs747816995 GRCh37: 2:1546370-1546370
GRCh38: 2:1542598-1542598
49 TPO NM_001206744.2(TPO):c.2499C>T (p.Asp833=) SNV Uncertain significance 331393 rs142148533 GRCh37: 2:1507832-1507832
GRCh38: 2:1504060-1504060
50 TPO NM_001206744.2(TPO):c.2212C>G (p.Gln738Glu) SNV Uncertain significance 331365 rs200796513 GRCh37: 2:1499966-1499966
GRCh38: 2:1496194-1496194

UniProtKB/Swiss-Prot genetic disease variations for Thyroid Dyshormonogenesis 2a:

72 (show all 24)
# Symbol AA change Variation ID SNP ID
1 TPO p.Tyr453Asp VAR_006060 rs121908083
2 TPO p.Glu799Lys VAR_006062 rs121908085
3 TPO p.Arg648Gln VAR_013138 rs121908086
4 TPO p.Ile447Phe VAR_015375 rs104893669
5 TPO p.Ala53Pro VAR_021622
6 TPO p.Asp240Asn VAR_021623 rs142702434
7 TPO p.Asn307Thr VAR_021624
8 TPO p.Ala326Thr VAR_021625 rs371367459
9 TPO p.Val433Met VAR_021626 rs103579111
10 TPO p.Leu458Pro VAR_021627 rs123187037
11 TPO p.Arg491His VAR_021628 rs201165648
12 TPO p.Gly493Ser VAR_021629 rs778515113
13 TPO p.Pro499Leu VAR_021630 rs116907218
14 TPO p.Trp527Cys VAR_021631 rs779434941
15 TPO p.Gln660Glu VAR_021632 rs121908088
16 TPO p.Arg665Trp VAR_021633 rs776742629
17 TPO p.Arg693Trp VAR_021634 rs121908087
18 TPO p.Gly771Arg VAR_021635 rs138931129
19 TPO p.Asp796Tyr VAR_021636
20 TPO p.Cys808Arg VAR_021637 rs935058009
21 TPO p.Glu378Lys VAR_025784 rs129731278
22 TPO p.Gly533Cys VAR_027229
23 TPO p.Gly590Ser VAR_027231 rs121908084
24 TPO p.Val839Ile VAR_027235 rs146351101

Expression for Thyroid Dyshormonogenesis 2a

Search GEO for disease gene expression data for Thyroid Dyshormonogenesis 2a.

Pathways for Thyroid Dyshormonogenesis 2a

GO Terms for Thyroid Dyshormonogenesis 2a

Sources for Thyroid Dyshormonogenesis 2a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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