CHNG6
MCID: HYP562
MIFTS: 32

Hypothyroidism, Congenital, Nongoitrous, 6 (CHNG6)

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

Aliases & Classifications for Hypothyroidism, Congenital, Nongoitrous, 6

MalaCards integrated aliases for Hypothyroidism, Congenital, Nongoitrous, 6:

Name: Hypothyroidism, Congenital, Nongoitrous, 6 56 29 13 6 71
Chng6 56 12 73
Hypothyroidism, Congenital, Non-Goitrous, 6 73
Congenital Nongoitrous Hypothyroidism 6 12

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
many features are present only in an untreated patient


HPO:

31
hypothyroidism, congenital, nongoitrous, 6:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Hypothyroidism, Congenital, Nongoitrous, 6

UniProtKB/Swiss-Prot : 73 Hypothyroidism, congenital, non-goitrous, 6: A disease characterized by growth retardation, developmental retardation, skeletal dysplasia, borderline low thyroxine levels and high triiodothyronine levels. There is differential sensitivity to thyroid hormone action, with retention of hormone responsiveness in the hypothalamic pituitary axis and liver but skeletal, gastrointestinal, and myocardial resistance.

MalaCards based summary : Hypothyroidism, Congenital, Nongoitrous, 6, is also known as chng6, and has symptoms including constipation and dry skin. An important gene associated with Hypothyroidism, Congenital, Nongoitrous, 6 is THRA (Thyroid Hormone Receptor Alpha), and among its related pathways/superpathways is Nuclear Receptor transcription pathway. Affiliated tissues include thyroid, liver and pituitary, and related phenotypes are hypertelorism and constipation

Disease Ontology : 12 A congenital hypothyroidism that has material basis in heterozygous mutation in the THRA gene on chromosome 17q21.1.

More information from OMIM: 614450 PS275200

Related Diseases for Hypothyroidism, Congenital, Nongoitrous, 6

Symptoms & Phenotypes for Hypothyroidism, Congenital, Nongoitrous, 6

Human phenotypes related to Hypothyroidism, Congenital, Nongoitrous, 6:

31 (show all 20)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 31 HP:0000316
2 constipation 31 HP:0002019
3 macroglossia 31 HP:0000158
4 delayed skeletal maturation 31 HP:0002750
5 anemia 31 HP:0001903
6 dry skin 31 HP:0000958
7 delayed eruption of teeth 31 HP:0000684
8 wormian bones 31 HP:0002645
9 growth delay 31 HP:0001510
10 congenital hip dislocation 31 HP:0001374
11 hoarse voice 31 HP:0001609
12 increased body weight 31 HP:0004324
13 omphalocele 31 HP:0001539
14 relative macrocephaly 31 HP:0004482
15 drowsiness 31 HP:0002329
16 congenital hypothyroidism 31 HP:0000851
17 broad-based gait 31 HP:0002136
18 increased body mass index 31 HP:0031418
19 impaired sensitivity to thyroid hormone 31 HP:0002930
20 increased t3/t4 ratio 31 HP:0012559

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
hypertelorism

Head And Neck Mouth:
macroglossia

Skin Nails Hair Skin:
dry skin
doughy skin (in some patients)

Abdomen External Features:
omphalocele

Neurologic Central Nervous System:
drowsiness
impairment of gross and fine motor coordination
slow reactions
difficulty with writing and drawing
slow, broad-based gait

Growth Other:
growth retardation

Skeletal Skull:
delayed bone age
multiple wormian bones
delayed fusion of cranial sutures
patent anterior fontanel

Head And Neck Nose:
low or flat nasal bridge

Cardiovascular Vascular:
low resting blood pressure
tortuosity of arteries of dorsal hands and feet (in some patients)

Muscle Soft Tissue:
reduced muscle tone but normal power

Neurologic Behavioral Psychiatric Manifestations:
placid affect

Metabolic Features:
decreased basal metabolic rate

Laboratory Abnormalities:
slightly elevated creatine kinase
slightly elevated cholesterol

Abdomen Gastrointestinal:
constipation
dilated bowel
delayed intestinal transit

Hematology:
anemia

Skeletal Pelvis:
congenital hip dislocation
absence of hip ossification centers

Head And Neck Head:
relative macrocephaly

Growth Weight:
increased body mass index

Head And Neck Teeth:
delayed tooth eruption

Growth Height:
growth deficit affecting lower segment of body

Cardiovascular Heart:
low resting heart rate

Skeletal Limbs:
decreased subischial leg length with normal sitting height
femoral epiphyseal dysgenesis
mild hypermobility and ligamentous laxity at knee and ankle

Neurologic Peripheral Nervous System:
slow deep tendon reflexes

Voice:
slow, monotonous speech
deep or hoarse voice

Endocrine Features:
total and free thyroxine low-normal or subnormal
total and free triiodothyronine high-normal or elevated
total thyroxine to total triiodothyronine ratio markedly low
free thyroxine to free triiodothyronine ratio markedly low
thyroid stimulating hormone normal
more

Clinical features from OMIM:

614450

UMLS symptoms related to Hypothyroidism, Congenital, Nongoitrous, 6:


constipation, dry skin

Drugs & Therapeutics for Hypothyroidism, Congenital, Nongoitrous, 6

Search Clinical Trials , NIH Clinical Center for Hypothyroidism, Congenital, Nongoitrous, 6

Genetic Tests for Hypothyroidism, Congenital, Nongoitrous, 6

Genetic tests related to Hypothyroidism, Congenital, Nongoitrous, 6:

# Genetic test Affiliating Genes
1 Hypothyroidism, Congenital, Nongoitrous, 6 29 THRA

Anatomical Context for Hypothyroidism, Congenital, Nongoitrous, 6

MalaCards organs/tissues related to Hypothyroidism, Congenital, Nongoitrous, 6:

40
Thyroid, Liver, Pituitary, Bone, Skin, Heart, Testes

Publications for Hypothyroidism, Congenital, Nongoitrous, 6

Articles related to Hypothyroidism, Congenital, Nongoitrous, 6:

# Title Authors PMID Year
1
Thyroid hormone resistance syndrome due to mutations in the thyroid hormone receptor α gene (THRA). 56 6
25670821 2015
2
Clinical phenotype and mutant TRα1. 56 6
22494134 2012
3
A mutation in the thyroid hormone receptor alpha gene. 56 6
22168587 2012

Variations for Hypothyroidism, Congenital, Nongoitrous, 6

ClinVar genetic disease variations for Hypothyroidism, Congenital, Nongoitrous, 6:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 THRA NM_001190919.1(THRA):c.1110+66C>ASNV Pathogenic 192271 rs876657394 17:38245652-38245652 17:40089399-40089399
2 THRA NM_001190919.1(THRA):c.1110+97G>ASNV Pathogenic 192272 rs876657395 17:38245683-38245683 17:40089430-40089430
3 THRA NM_001190919.1(THRA):c.1110+83C>GSNV Pathogenic 192273 rs876657396 17:38245669-38245669 17:40089416-40089416
4 THRA NM_001190919.1(THRA):c.134G>T (p.Ser45Ile)SNV Pathogenic 29913 rs137853162 17:38233773-38233773 17:40077520-40077520
5 THRA NM_001190919.1(THRA):c.1110G>C (p.Lys370Asn)SNV Pathogenic 29914 rs137853163 17:38245586-38245586 17:40089333-40089333
6 THRA NM_001190919.1(THRA):c.54-1G>ASNV Conflicting interpretations of pathogenicity 561132 rs199530759 17:38233123-38233123 17:40076870-40076870
7 THRA NM_199334.5(THRA):c.425G>T (p.Arg142Leu)SNV Uncertain significance 803389 17:38240917-38240917 17:40084664-40084664
8 THRA NM_021724.5(NR1D1):c.1653G>A (p.Ser551=)SNV Uncertain significance 225490 rs201037953 17:38249528-38249528 17:40093275-40093275

UniProtKB/Swiss-Prot genetic disease variations for Hypothyroidism, Congenital, Nongoitrous, 6:

73
# Symbol AA change Variation ID SNP ID
1 THRA p.Ala263Val VAR_074559 rs155554503
2 THRA p.Asn359Tyr VAR_074560

Expression for Hypothyroidism, Congenital, Nongoitrous, 6

Search GEO for disease gene expression data for Hypothyroidism, Congenital, Nongoitrous, 6.

Pathways for Hypothyroidism, Congenital, Nongoitrous, 6

Pathways related to Hypothyroidism, Congenital, Nongoitrous, 6 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.58 THRA NR1D1

GO Terms for Hypothyroidism, Congenital, Nongoitrous, 6

Cellular components related to Hypothyroidism, Congenital, Nongoitrous, 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II transcription factor complex GO:0090575 8.62 THRA NR1D1

Biological processes related to Hypothyroidism, Congenital, Nongoitrous, 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription, DNA-templated GO:0045892 9.37 THRA NR1D1
2 transcription initiation from RNA polymerase II promoter GO:0006367 9.32 THRA NR1D1
3 steroid hormone mediated signaling pathway GO:0043401 9.26 THRA NR1D1
4 hormone-mediated signaling pathway GO:0009755 9.16 THRA NR1D1
5 intracellular receptor signaling pathway GO:0030522 8.96 THRA NR1D1
6 response to lipid GO:0033993 8.62 THRA NR1D1

Molecular functions related to Hypothyroidism, Congenital, Nongoitrous, 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sequence-specific DNA binding GO:0043565 9.46 THRA NR1D1
2 transcription factor binding GO:0008134 9.43 THRA NR1D1
3 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 9.4 THRA NR1D1
4 transcription regulatory region DNA binding GO:0044212 9.37 THRA NR1D1
5 signaling receptor activity GO:0038023 9.32 THRA NR1D1
6 transcription regulatory region sequence-specific DNA binding GO:0000976 9.26 THRA NR1D1
7 nuclear receptor transcription coactivator activity GO:0030374 9.16 THRA NR1D1
8 steroid hormone receptor activity GO:0003707 8.96 THRA NR1D1
9 nuclear receptor activity GO:0004879 8.62 THRA NR1D1

Sources for Hypothyroidism, Congenital, Nongoitrous, 6

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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