CHNG2
MCID: HYP760
MIFTS: 54

Hypothyroidism, Congenital, Nongoitrous, 2 (CHNG2)

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

Aliases & Classifications for Hypothyroidism, Congenital, Nongoitrous, 2

MalaCards integrated aliases for Hypothyroidism, Congenital, Nongoitrous, 2:

Name: Hypothyroidism, Congenital, Nongoitrous, 2 57 29 6
Thyroid Dysgenesis 57 20 72 44 70
Thyroid Hypoplasia 57 20 58 70
Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia 57 29 13
Thyrotropin Resistance 57 72 6
Thyroid Hemiagenesis 58 6 70
Thyroid Agenesis 57 73 20
Chng2 57 12 72
Congenital Nongoitrous Hypothyroidism 2 12 15
Athyreotic Hypothyroidism 57 72
Thyroid, Ectopic 57 20
Rtsh 57 72
Congenital Hypothyroidism Due to Thyroid Dysgenesis or Hypoplasia 12
Hypothyroidism, Congenital, Due to Thyroid Dysgenesis 57
Congenital Hypothyroidism Due to Thyroid Dysgenesis 72
Hypothyroidism, Congenital, Non-Goitrous, 2 72
Hypothyroidism, Congenital, Nongoitrous, 1 70
Hypothyroidism, Congenital, Nongoitrous, 3 70
Thyroid-Stimulating Hormone Resistance 72
Thyroid Hormone Resistance Syndrome 70
Hypothyroidism, Athyreotic 57
Resistance to Thyrotropin 57
Thyrotropin; Rtsh 57
Thyroid Ectopic 54

Characteristics:

Orphanet epidemiological data:

58
thyroid hypoplasia
Prevalence: 1-9/100000 (Worldwide);

OMIM®:

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

Miscellaneous:
intrafamilial phenotypic variability
incomplete penetrance (in some families)
sensitivity to cold (if untreated)
progressive reduction in thyroid size (in some patients)


HPO:

31
hypothyroidism, congenital, nongoitrous, 2:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare endocrine diseases


Summaries for Hypothyroidism, Congenital, Nongoitrous, 2

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 95720 Definition Thyroid hypoplasia is a form of thyroid dysgenesis (see this term) characterized by incomplete development of the thyroid gland that results in primary congenital hypothyroidism (see this term), a permanent thyroid deficiency that is present from birth. Epidemiology Prevalence is estimated at around 1/28,000. Thyroid hypoplasia and athyreosis (see this term) combined account for one-third of cases of thyroid dysgenesis. Clinical description Clinical manifestations of thyroid hypoplasia are often subtle or not present at birth, probably as a result of trans-placental passage of some maternal thyroid hormone or due to the fact that many infants have some thyroid production of their own. More specific symptoms and signs do not develop until several months of age. Common clinical features and signs include decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice, myxedematous facies, large fontanels (especially posterior), macroglossia, a distended abdomen with umbilical hernia, and hypotonia. Goiter is always absent. Slow linear growth and developmental delay are usually apparent by 4-6 months of age. Without treatment thyroid hypoplasia results in severe intellectual deficit and short stature. Etiology Familial cases of thyroid hypoplasia are caused by mutations in the FOXE1, NKX2-1, NKX2-5 or PAX8 genes (9q22, 14q13, 5q34 and 2q12-q14). Mutations that result in partial inactivation of the TSHR gene (14q31) can present with thyroid hypoplasia. Diagnostic methods Imaging studies are required to confirm the diagnosis. Genetic counseling Thyroid hypoplasia is generally thought to be sporadic. However, recent evidence points to the possibility of a genetic component. Around 2% of cases have been shown to be familial.

MalaCards based summary : Hypothyroidism, Congenital, Nongoitrous, 2, also known as thyroid dysgenesis, is related to hypothyroidism, thyroidal or athyroidal, with spiky hair and cleft palate and nodular goiter. An important gene associated with Hypothyroidism, Congenital, Nongoitrous, 2 is PAX8 (Paired Box 8), and among its related pathways/superpathways are Aldosterone synthesis and secretion and Thyroxine (Thyroid Hormone) Production. The drug Hormones has been mentioned in the context of this disorder. Affiliated tissues include thyroid, tongue and heart, and related phenotypes are constipation and hypothyroidism

Disease Ontology : 12 A congenital hypothyroidism that has material basis in heterozygous mutation in the PAX8 gene on chromosome 2q13.

OMIM® : 57 In 80 to 85% of cases, congenital hypothyroidism is associated with, and presumably is a consequence of, thyroid dysgenesis. In these cases, the thyroid gland can be absent (agenesis), ectopically located, and/or severely reduced in size (hypoplasia). When thyroid hormone therapy is not initiated within the first 2 months of life, congenital hypothyroidism can cause severe neurologic, mental, and motor damage (Macchia et al., 1998). (218700) (Updated 20-May-2021)

UniProtKB/Swiss-Prot : 72 Hypothyroidism, congenital, non-goitrous, 2: A disease characterized by thyroid dysgenesis, the most frequent cause of congenital hypothyroidism, accounting for 85% of case. The thyroid gland can be completely absent (athyreosis), ectopically located and/or severely hypoplastic. Ectopic thyroid gland is the most frequent malformation, with thyroid tissue being found most often at the base of the tongue.

Wikipedia : 73 Thyroid dysgenesis is a cause of congenital hypothyroidism where the thyroid is missing, ectopic, or... more...

Related Diseases for Hypothyroidism, Congenital, Nongoitrous, 2

Diseases in the Hypothyroidism, Congenital, Nongoitrous, 2 family:

Hypothyroidism, Congenital, Nongoitrous, 5 Hypothyroidism, Congenital, Nongoitrous, 4
Hypothyroidism, Congenital, Nongoitrous, 1 Hypothyroidism, Congenital, Nongoitrous, 8
Hypothyroidism, Congenital, Nongoitrous, 9 Hypothyroidism, Congenital, Nongoitrous, 3
Hypothyroidism, Congenital, Nongoitrous, 6 Hypothyroidism, Congenital, Nongoitrous, 7

Diseases related to Hypothyroidism, Congenital, Nongoitrous, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 146)
# Related Disease Score Top Affiliating Genes
1 hypothyroidism, thyroidal or athyroidal, with spiky hair and cleft palate 31.0 SLC26A4 PAX8 NKX2-1 FOXE1
2 nodular goiter 30.8 TSHR TG
3 graves disease 1 30.6 TSHR TG
4 subacute thyroiditis 30.2 TSHR TG
5 thyroid ectopia 30.1 PAX8-AS1 PAX8
6 congenital hypothyroidism 30.1 TSHR TG SLC26A4 PAX8-AS1 PAX8 NKX2-1
7 hashimoto thyroiditis 30.1 TSHR TG SLC26A4
8 multinodular goiter 30.0 TSHR TG SLC26A4 PAX8 NKX2-1
9 endemic goiter 30.0 TSHR TG SLC26A4
10 thyroid carcinoma 29.8 TSHR TG SLC26A4 PAX8 NKX2-1
11 hyperthyroidism 29.8 TSHR TG CEP128
12 thyroid gland medullary carcinoma 29.7 TG PAX8 NKX2-1
13 myxedema 29.7 TSHR TG
14 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 29.6 TSHR TG
15 ectopic thymus 29.6 TG NKX2-1
16 pendred syndrome 29.6 TG SLC26A4 PAX8
17 graves' disease 29.5 TSHR TG PAX8
18 primary congenital hypothyroidism 29.4 TSHR PAX8 NKX2-1 FOXE1
19 goiter 29.4 TSHR TG SLC26A4 PAX8 NKX2-1
20 thyroid carcinoma, familial medullary 29.3 TG NKX2-1
21 papillary carcinoma 29.1 TSHR TG PAX8 NKX2-1
22 follicular adenoma 29.1 TSHR TG SLC26A4 PAX8 NKX2-1
23 hypothyroidism 29.1 TSHR TG SLC26A4 PAX8-AS1 PAX8 NKX2-1
24 athyreosis 29.1 TSHR TG SLC26A4 PAX8 NKX2-1 FOXE1
25 thyroid gland disease 29.1 TSHR TG SLC26A4 PAX8 NKX2-1 FOXE1
26 hypothyroidism, congenital, nongoitrous, 1 28.9 TSHR TG PAX8 FOXE1 CEP128
27 hypothyroidism, congenital, nongoitrous, 7 11.4
28 hypothyroidism, congenital, nongoitrous, 3 11.2
29 bamforth syndrome 11.2
30 thyroiditis 10.6
31 thyroid cancer, nonmedullary, 1 10.3
32 hyperthyroidism, nonautoimmune 10.2 TSHR CEP128
33 permanent congenital hypothyroidism 10.2
34 thymus basaloid carcinoma 10.2 PAX8 NKX2-1
35 thymus clear cell carcinoma 10.1 PAX8 NKX2-1
36 tremor 10.1
37 peritoneal serous adenocarcinoma 10.1 PAX8 NKX2-1
38 atypical follicular adenoma 10.1 TG PAX8
39 thyroid sarcoma 10.1 TG PAX8
40 iodine hypothyroidism 10.1 TSHR TG
41 clear cell adenoma 10.1 TG PAX8
42 thyroid crisis 10.1 TSHR TG
43 toxic diffuse goiter 10.1 TSHR TG
44 subacute lymphocytic thyroiditis 10.1 TSHR TG
45 pseudohypoparathyroidism, type ia 10.0
46 pseudopseudohypoparathyroidism 10.0
47 leptin deficiency or dysfunction 10.0
48 ovarian benign neoplasm 10.0 TG PAX8
49 plummer's disease 10.0 TSHR TG
50 suppurative thyroiditis 10.0 TSHR TG

Graphical network of the top 20 diseases related to Hypothyroidism, Congenital, Nongoitrous, 2:



Diseases related to Hypothyroidism, Congenital, Nongoitrous, 2

Symptoms & Phenotypes for Hypothyroidism, Congenital, Nongoitrous, 2

Human phenotypes related to Hypothyroidism, Congenital, Nongoitrous, 2:

58 31 (show all 34)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 constipation 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0002019
2 hypothyroidism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000821
3 macroglossia 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000158
4 coarse facial features 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000280
5 global developmental delay 58 31 hallmark (90%) Frequent (79-30%),Very frequent (99-80%) HP:0001263
6 umbilical hernia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001537
7 fatigue 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0012378
8 growth delay 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001510
9 jaundice 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000952
10 large fontanelles 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000239
11 thyroid hypoplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0005990
12 hypersomnia 58 31 hallmark (90%) Very frequent (99-80%) HP:0100786
13 abdominal distention 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0003270
14 thyroid agenesis 58 31 hallmark (90%) Very frequent (99-80%) HP:0008191
15 hypotonia 31 hallmark (90%) HP:0001252
16 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
17 intellectual disability, severe 58 31 frequent (33%) Frequent (79-30%) HP:0010864
18 hypothermia 31 HP:0002045
19 muscular hypotonia 58 Very frequent (99-80%),Very frequent (99-80%)
20 delayed skeletal maturation 31 HP:0002750
21 feeding difficulties in infancy 31 HP:0008872
22 dry skin 31 HP:0000958
23 abnormality of the face 58 Very frequent (99-80%),Very frequent (99-80%)
24 goiter 31 HP:0000853
25 lethargy 31 HP:0001254
26 hyperbilirubinemia 31 HP:0002904
27 stridor 31 HP:0010307
28 generalized hypotonia 31 HP:0001290
29 hoarse cry 31 HP:0001615
30 large posterior fontanelle 31 HP:0004491
31 congenital hypothyroidism 31 HP:0000851
32 ectopic thyroid 31 HP:0100028
33 increased thyroid-stimulating hormone level 31 HP:0002925
34 bradycardia 31 HP:0001662

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Other:
failure to thrive (if untreated)

Neurologic Central Nervous System:
delayed intellectual development (if untreated)
fatigue (if untreated)

Abdomen Gastrointestinal:
constipation (if untreated)

Endocrine Features:
hypothyroidism, congenital
normal-sized to hypoplastic or absent thyroid gland
ectopic thyroid gland (in some patients)
elevated tsh levels
normal to elevated thyroglobulin levels
more

Clinical features from OMIM®:

218700 (Updated 20-May-2021)

MGI Mouse Phenotypes related to Hypothyroidism, Congenital, Nongoitrous, 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.17 FOXE1 NKX2-1 PAX8 SLC26A4 TG TSHR

Drugs & Therapeutics for Hypothyroidism, Congenital, Nongoitrous, 2

Drugs for Hypothyroidism, Congenital, Nongoitrous, 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Hormones Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Utility of Recombinant Human Thyrotropin (rTSH) PET-CT Fusion Scanning to Identify Residual Well-differentiated Epithelial Thyroid Cancer Completed NCT00181168 Phase 2 Euthyroid Group
2 Phenotype and Genotype Analysis in Congenital Hypothyroidism Due to Thyroid Dysgenesis. The Use of Genetic Analysis in the Early Care of Children With Thyroid Dysgenesis Completed NCT01916018
3 Congenital Hypothyroidism in Children With Eutopic Gland or Thyroid Hemiagenesis: Predictive Factors for Transient vs Permanent Hypothyroidism. Recruiting NCT04712760
4 Growing up With the Young Endocrine Support System (YESS!): Innovative E-technology to Improve Transition From Paediatric to Adult Care Not yet recruiting NCT04252001

Search NIH Clinical Center for Hypothyroidism, Congenital, Nongoitrous, 2

Cochrane evidence based reviews: thyroid dysgenesis

Genetic Tests for Hypothyroidism, Congenital, Nongoitrous, 2

Genetic tests related to Hypothyroidism, Congenital, Nongoitrous, 2:

# Genetic test Affiliating Genes
1 Hypothyroidism, Congenital, Nongoitrous, 2 29 PAX8
2 Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia 29

Anatomical Context for Hypothyroidism, Congenital, Nongoitrous, 2

MalaCards organs/tissues related to Hypothyroidism, Congenital, Nongoitrous, 2:

40
Thyroid, Tongue, Heart, Thymus, Uterus, Brain, Lung

Publications for Hypothyroidism, Congenital, Nongoitrous, 2

Articles related to Hypothyroidism, Congenital, Nongoitrous, 2:

(show top 50) (show all 365)
# Title Authors PMID Year
1
Characterization of a novel loss of function mutation of PAX8 in a familial case of congenital hypothyroidism with in-place, normal-sized thyroid. 54 61 57 6
15356023 2004
2
PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis. 61 6 54 57
9590296 1998
3
Thyroid transcription factor 1 rescues PAX8/p300 synergism impaired by a natural PAX8 paired domain mutation with dominant negative activity. 61 6 57
15718293 2005
4
Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8. 57 61 6
11232006 2001
5
A novel mutation (Q40P) in PAX8 associated with congenital hypothyroidism and thyroid hypoplasia: evidence for phenotypic variability in mother and child. 6 57
11502839 2001
6
Mutations in the gene encoding thyroid transcription factor-1 (TTF-1) are not a frequent cause of congenital hypothyroidism (CH) with thyroid dysgenesis. 61 54 57
9226207 1997
7
Next-generation sequencing analysis of TSHR in 384 Chinese subclinical congenital hypothyroidism (CH) and CH patients. 61 6
27637299 2016
8
TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis. 6 61
22876533 2012
9
Genetics of congenital hypothyroidism. 61 57
15863666 2005
10
Linkage and mutational analysis of familial thyroid dysgenesis demonstrate genetic heterogeneity implicating novel genes. 61 57
15547625 2005
11
Thyroid development and its disorders: genetics and molecular mechanisms. 57 61
15466939 2004
12
Discordance of monozygotic twins for thyroid dysgenesis: implications for screening and for molecular pathophysiology. 61 57
12213848 2002
13
Thyroid developmental anomalies in first degree relatives of children with congenital hypothyroidism. 61 57
11836288 2002
14
Nineteen years of national screening for congenital hypothyroidism: familial cases with thyroid dysgenesis suggest the involvement of genetic factors. 61 57
11344199 2001
15
Familial forms of thyroid dysgenesis among infants with congenital hypothyroidism. 61 57
10939901 2000
16
Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia. 57 54
9697705 1998
17
Mutations of the human thyrotropin receptor gene causing thyroid hypoplasia and persistent congenital hypothyroidism. 6 61
9329388 1997
18
Thyroid dysgenesis in two pairs of monozygotic twins and in a mother and child. 57 61
5959523 1966
19
The role of thyroid dysgenesis and maldescent in the etiology of sporadic cretinism. 61 57
13896077 1962
20
Mutations in proteasome-related genes are associated with thyroid hemiagenesis. 6
28390009 2017
21
Poorly Controlled Congenital Hypothyroidism due to an Underlying Allgrove Syndrome. 6
27255745 2016
22
The Italian screening program for primary congenital hypothyroidism: actions to improve screening, diagnosis, follow-up, and surveillance. 6
23404215 2013
23
R450H TSH receptor mutation in congenital hypothyroidism in Taiwanese children. 6
22405933 2012
24
Molecular screening of the TSH receptor (TSHR) and thyroid peroxidase (TPO) genes in Korean patients with nonsyndromic congenital hypothyroidism. 6
21707688 2011
25
Nonclassic TSH resistance: TSHR mutation carriers with discrepantly high thyroidal iodine uptake. 6
21677043 2011
26
The R450H mutation and D727E polymorphism of the thyrotropin receptor gene in a Chinese child with congenital hypothyroidism. 6
21714469 2010
27
Novel TSHR mutations in consanguineous families with congenital nongoitrous hypothyroidism. 6
20718767 2010
28
Longitudinal evaluation of patients with a homozygous R450H mutation of the TSH receptor gene. 6
19506388 2009
29
Subclinical hypothyroidism caused by a mutation of the thyrotropin receptor gene. 6
15693879 2005
30
Congenital hypothyroidism and apparent athyreosis with compound heterozygosity or compensated hypothyroidism with probable hemizygosity for inactivating mutations of the TSH receptor. 6
14725684 2004
31
The W546X mutation of the thyrotropin receptor gene: potential major contributor to thyroid dysfunction in a Caucasian population. 6
12629076 2003
32
Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism. 6
12050212 2002
33
Novel inactivating missense mutations in the thyrotropin receptor gene in Japanese children with resistance to thyrotropin. 6
11442002 2001
34
A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH. 6
11095460 2000
35
Congenital hypothyroidism with impaired thyroid response to thyrotropin (TSH) and absent circulating thyroglobulin: evidence for a new inactivating mutation of the TSH receptor gene. 6
10720030 2000
36
Apparent congenital athyreosis contrasting with normal plasma thyroglobulin levels and associated with inactivating mutations in the thyrotropin receptor gene: are athyreosis and ectopic thyroid distinct entities? 6
9589691 1998
37
Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland. 6
9185526 1997
38
Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH. 6
9100579 1997
39
Four families with loss of function mutations of the thyrotropin receptor. 6
8954020 1996
40
A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism. 6
8964822 1996
41
Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene. 6
7528344 1995
42
Congenital hypothyroidism presenting as apparent spondyloepiphyseal dysplasia. 57
8256805 1993
43
Congenital hypothyroidism and growth hormone deficiency. 57
2904599 1988
44
Intratracheal thyroid--familial occurrence. 57
3965830 1985
45
Second International Conference on Neonatal Thyroid Screening: progress report. 57
6842320 1983
46
Racial differences in the incidence of congenital hypothyroidism. 57
7310589 1981
47
[Epidemiology of hypothyroidism due to congenital malformation of the gland: athyreosis or ectopic thyroid (author's transl)]. 57
7332439 1981
48
Familial thyroid ectopy and hemiagenesis. 57
7436522 1980
49
Ectopic thyroid gland. A clinical study of 30 children and review. 57
202687 1978
50
Familial agoitrous cretinism accompanied by musclar hypertrophy. 57
5637792 1968

Variations for Hypothyroidism, Congenital, Nongoitrous, 2

ClinVar genetic disease variations for Hypothyroidism, Congenital, Nongoitrous, 2:

6 (show top 50) (show all 227)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TSHR TSHR, 18-BP DEL, 4-BP INS Indel Pathogenic 6447 GRCh37:
GRCh38:
2 TSHR TSHR, 2-BP DEL, 654AC Deletion Pathogenic 6460 GRCh37:
GRCh38:
3 TSHR NM_000369.5(TSHR):c.1430C>T (p.Thr477Ile) SNV Pathogenic 6455 rs121908881 GRCh37: 14:81609832-81609832
GRCh38: 14:81143488-81143488
4 TSHR NM_000369.5(TSHR):c.928C>T (p.Arg310Cys) SNV Pathogenic 6456 rs121908882 GRCh37: 14:81609330-81609330
GRCh38: 14:81142986-81142986
5 TSHR NM_000369.5(TSHR):c.1798T>C (p.Cys600Arg) SNV Pathogenic 6458 rs121908884 GRCh37: 14:81610200-81610200
GRCh38: 14:81143856-81143856
6 TSHR NM_000369.5(TSHR):c.1400T>C (p.Leu467Pro) SNV Pathogenic 6459 rs121908885 GRCh37: 14:81609802-81609802
GRCh38: 14:81143458-81143458
7 TSHR NM_000369.5(TSHR):c.545+3G>C SNV Pathogenic 6461 rs786205080 GRCh37: 14:81558955-81558955
GRCh38: 14:81092611-81092611
8 TSHR NM_000369.5(TSHR):c.545+5G>T SNV Pathogenic 917858 GRCh37: 14:81558957-81558957
GRCh38: 14:81092613-81092613
9 PAX8-AS1 , PAX8 NM_003466.4(PAX8):c.322C>T (p.Arg108Ter) SNV Pathogenic 13783 rs104893655 GRCh37: 2:114002071-114002071
GRCh38: 2:113244494-113244494
10 PAX8-AS1 , PAX8 NM_003466.4(PAX8):c.92G>A (p.Arg31His) SNV Pathogenic 13784 rs104893657 GRCh37: 2:114004430-114004430
GRCh38: 2:113246853-113246853
11 PAX8-AS1 , PAX8 NM_003466.4(PAX8):c.185T>G (p.Leu62Arg) SNV Pathogenic 13785 rs104893658 GRCh37: 2:114004337-114004337
GRCh38: 2:113246760-113246760
12 PAX8-AS1 , PAX8 NM_003466.4(PAX8):c.170G>A (p.Cys57Tyr) SNV Pathogenic 13786 rs104893659 GRCh37: 2:114004352-114004352
GRCh38: 2:113246775-113246775
13 PAX8-AS1 , PAX8 NM_003466.4(PAX8):c.160A>G (p.Ser54Gly) SNV Pathogenic 13787 rs104893660 GRCh37: 2:114004362-114004362
GRCh38: 2:113246785-113246785
14 PAX8-AS1 , PAX8 NM_003466.4(PAX8):c.119A>C (p.Gln40Pro) SNV Pathogenic 13788 rs104893656 GRCh37: 2:114004403-114004403
GRCh38: 2:113246826-113246826
15 CEP128 , TSHR NM_000369.5(TSHR):c.122G>C (p.Cys41Ser) SNV Pathogenic 6442 rs121908869 GRCh37: 14:81422146-81422146
GRCh38: 14:80955802-80955802
16 TSHR NM_000369.5(TSHR):c.1637G>A (p.Trp546Ter) SNV Pathogenic 6439 rs121908866 GRCh37: 14:81610039-81610039
GRCh38: 14:81143695-81143695
17 PAX8-AS1 , PAX8 NM_003466.4(PAX8):c.143C>T (p.Ser48Phe) SNV Pathogenic 13789 rs121917719 GRCh37: 2:114004379-114004379
GRCh38: 2:113246802-113246802
18 TSHR NM_000369.5(TSHR):c.1170T>G (p.Cys390Trp) SNV Pathogenic 6444 rs121908871 GRCh37: 14:81609572-81609572
GRCh38: 14:81143228-81143228
19 TSHR NM_000369.5(TSHR):c.1575C>A (p.Phe525Leu) SNV Pathogenic 6443 rs121908870 GRCh37: 14:81609977-81609977
GRCh38: 14:81143633-81143633
20 TSHR NM_000369.5(TSHR):c.1228G>A (p.Asp410Asn) SNV Pathogenic 6441 rs121908868 GRCh37: 14:81609630-81609630
GRCh38: 14:81143286-81143286
21 TSHR NM_000369.5(TSHR):c.970C>T (p.Gln324Ter) SNV Pathogenic 6440 rs121908867 GRCh37: 14:81609372-81609372
GRCh38: 14:81143028-81143028
22 TSHR NM_000369.5(TSHR):c.326G>A (p.Arg109Gln) SNV Pathogenic 6438 rs121908865 GRCh37: 14:81554306-81554306
GRCh38: 14:81087962-81087962
23 TSHR NM_000369.5(TSHR):c.484C>G (p.Pro162Ala) SNV Pathogenic 6435 rs121908863 GRCh37: 14:81558891-81558891
GRCh38: 14:81092547-81092547
24 TSHR NM_000369.5(TSHR):c.500T>A (p.Ile167Asn) SNV Pathogenic 6434 rs121908862 GRCh37: 14:81558907-81558907
GRCh38: 14:81092563-81092563
25 PAX8-AS1 , PAX8 NM_003466.4(PAX8):c.457_458del (p.Leu153fs) Deletion Pathogenic 915465 GRCh37: 2:114000287-114000288
GRCh38: 2:113242710-113242711
26 TSHR NM_000369.5(TSHR):c.1349G>A (p.Arg450His) SNV Pathogenic 225505 rs189261858 GRCh37: 14:81609751-81609751
GRCh38: 14:81143407-81143407
27 PAX8-AS1 , PAX8 NM_003466.4(PAX8):c.236C>T (p.Ser79Phe) SNV Likely pathogenic 915464 GRCh37: 2:114002157-114002157
GRCh38: 2:113244580-113244580
28 PAX8 NM_003466.4(PAX8):c.203C>T (p.Thr68Ile) SNV Likely pathogenic 872942 GRCh37:
GRCh38:
29 PSMD3 GRCh37/hg19 17q21.1(chr17:38146929-38153473)x1 copy number loss Likely pathogenic 369988 GRCh37: 17:38146929-38153473
GRCh38:
30 overlap with 4 genes GRCh37/hg19 14q23.1(chr14:58737402-58891576)x1 copy number loss Likely pathogenic 369985 GRCh37: 14:58737402-58891576
GRCh38:
31 overlap with 4 genes GRCh37/hg19 11p15.2(chr11:14504463-14909461)x1 copy number loss Likely pathogenic 369982 GRCh37: 11:14504463-14909461
GRCh38:
32 overlap with 3 genes GRCh37/hg19 11p15.2(chr11:14657389-14918308)x1 copy number loss Likely pathogenic 369983 GRCh37: 11:14657389-14918308
GRCh38:
33 LINC01121 GRCh37/hg19 2p21(chr2:45453858-45455897)x3 copy number gain Likely pathogenic 369989 GRCh37: 2:45453858-45455897
GRCh38:
34 VPS13C GRCh37/hg19 15q22.2(chr15:62128861-62340126)x1 copy number loss Likely pathogenic 369986 GRCh37: 15:62128861-62340126
GRCh38:
35 overlap with 4 genes GRCh37/hg19 14q23.1(chr14:58737402-58884615)x1 copy number loss Likely pathogenic 369984 GRCh37: 14:58737402-58884615
GRCh38:
36 LINC01121 GRCh37/hg19 2p21(chr2:45454554-45457111)x3 copy number gain Likely pathogenic 369990 GRCh37: 2:45454554-45457111
GRCh38:
37 VPS13C GRCh37/hg19 15q22.2(chr15:62155282-62332980)x1 copy number loss Likely pathogenic 369987 GRCh37: 15:62155282-62332980
GRCh38:
38 PAX8-AS1 , PAX8 NM_003466.4(PAX8):c.160A>T (p.Ser54Cys) SNV Likely pathogenic 436165 rs104893660 GRCh37: 2:114004362-114004362
GRCh38: 2:113246785-113246785
39 TSHR NM_000369.5(TSHR):c.1657G>A (p.Ala553Thr) SNV Likely pathogenic 6445 rs121908872 GRCh37: 14:81610059-81610059
GRCh38: 14:81143715-81143715
40 TSHR NM_000369.5(TSHR):c.1960A>T (p.Ile654Phe) SNV Likely pathogenic 917861 GRCh37: 14:81610362-81610362
GRCh38: 14:81144018-81144018
41 TSHR NM_000369.5(TSHR):c.545+2_545+3del Microsatellite Likely pathogenic 189249 rs786204790 GRCh37: 14:81558952-81558953
GRCh38: 14:81092608-81092609
42 TSHR NM_000369.5(TSHR):c.202C>T (p.Pro68Ser) SNV Conflicting interpretations of pathogenicity 437071 rs142063461 GRCh37: 14:81528523-81528523
GRCh38: 14:81062179-81062179
43 PAX8 NM_003466.4(PAX8):c.1028A>G (p.Asn343Ser) SNV Conflicting interpretations of pathogenicity 801740 rs374652916 GRCh37: 2:113993030-113993030
GRCh38: 2:113235453-113235453
44 TSHR NM_000369.5(TSHR):c.*1580A>G SNV Uncertain significance 314720 rs189084497 GRCh37: 14:81612277-81612277
GRCh38: 14:81145933-81145933
45 TSHR NM_000369.5(TSHR):c.1600C>T (p.Arg534Cys) SNV Uncertain significance 135394 rs150602845 GRCh37: 14:81610002-81610002
GRCh38: 14:81143658-81143658
46 TSHR NM_000369.5(TSHR):c.463A>T (p.Ile155Leu) SNV Uncertain significance 888396 GRCh37: 14:81557483-81557483
GRCh38: 14:81091139-81091139
47 PAX8 NM_003466.4(PAX8):c.*1942C>T SNV Uncertain significance 892910 GRCh37: 2:113974168-113974168
GRCh38: 2:113216591-113216591
48 PAX8 NM_003466.4(PAX8):c.*1490G>A SNV Uncertain significance 892911 GRCh37: 2:113974620-113974620
GRCh38: 2:113217043-113217043
49 PAX8 NM_003466.4(PAX8):c.*1457G>A SNV Uncertain significance 892912 GRCh37: 2:113974653-113974653
GRCh38: 2:113217076-113217076
50 PAX8-AS1 , PAX8 NM_003466.4(PAX8):c.700G>A (p.Glu234Lys) SNV Uncertain significance 894420 GRCh37: 2:113999205-113999205
GRCh38: 2:113241628-113241628

UniProtKB/Swiss-Prot genetic disease variations for Hypothyroidism, Congenital, Nongoitrous, 2:

72
# Symbol AA change Variation ID SNP ID
1 PAX8 p.Arg31His VAR_012769 rs104893657
2 PAX8 p.Gln40Pro VAR_012770 rs104893656
3 PAX8 p.Cys57Tyr VAR_012771 rs104893659
4 PAX8 p.Leu62Arg VAR_012772 rs104893658

Expression for Hypothyroidism, Congenital, Nongoitrous, 2

Search GEO for disease gene expression data for Hypothyroidism, Congenital, Nongoitrous, 2.

Pathways for Hypothyroidism, Congenital, Nongoitrous, 2

Pathways related to Hypothyroidism, Congenital, Nongoitrous, 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.03 TSHR TG SLC26A4 PAX8
2 9.4 TSHR TG

GO Terms for Hypothyroidism, Congenital, Nongoitrous, 2

Biological processes related to Hypothyroidism, Congenital, Nongoitrous, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 thyroid hormone generation GO:0006590 9.26 TG FOXE1
2 iodide transport GO:0015705 9.16 TG SLC26A4
3 thyroid-stimulating hormone signaling pathway GO:0038194 8.96 TSHR PAX8
4 thyroid gland development GO:0030878 8.92 TG PAX8 NKX2-1 FOXE1

Molecular functions related to Hypothyroidism, Congenital, Nongoitrous, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 thyroid-stimulating hormone receptor activity GO:0004996 8.62 TSHR PAX8

Sources for Hypothyroidism, Congenital, Nongoitrous, 2

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
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35 IUPHAR
36 KEGG
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46 MGI
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56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
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68 SNOMED-CT via HPO
69 Tocris
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71 UMLS via Orphanet
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