CHNG6
MCID: HYP562
MIFTS: 38

Hypothyroidism, Congenital, Nongoitrous, 6 (CHNG6)

Categories: Bone diseases, Ear 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 57 29 13 6 70
Chng6 57 12 72
Congenital Nongoitrous Hypothyroidism 6 12 15
Hypothyroidism, Congenital, Nongoitrous, Type 6 39
Hypothyroidism, Congenital, Non-Goitrous, 6 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
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 : 72 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, also known as chng6, is related to thrombasthenia and retinal ischemia, 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 are Colorectal Cancer Metastasis and Amyotrophic lateral sclerosis (ALS). Affiliated tissues include thyroid, pituitary and bone, and related phenotypes are constipation and macroglossia

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

Graphical network of the top 20 diseases related to Hypothyroidism, Congenital, Nongoitrous, 6:



Diseases related to 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 constipation 31 HP:0002019
2 macroglossia 31 HP:0000158
3 delayed skeletal maturation 31 HP:0002750
4 hypertelorism 31 HP:0000316
5 anemia 31 HP:0001903
6 dry skin 31 HP:0000958
7 growth delay 31 HP:0001510
8 congenital hip dislocation 31 HP:0001374
9 delayed eruption of teeth 31 HP:0000684
10 hoarse voice 31 HP:0001609
11 wormian bones 31 HP:0002645
12 omphalocele 31 HP:0001539
13 broad-based gait 31 HP:0002136
14 relative macrocephaly 31 HP:0004482
15 congenital hypothyroidism 31 HP:0000851
16 drowsiness 31 HP:0002329
17 increased body weight 31 HP:0004324
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®:

57 (Updated 05-Apr-2021)
Abdomen Gastrointestinal:
constipation
dilated bowel
delayed intestinal transit

Head And Neck Eyes:
hypertelorism

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

Head And Neck Mouth:
macroglossia

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 (Updated 05-Apr-2021)

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


constipation; dry skin

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased viability with paclitaxel GR00179-A-1 8.32 CASP3

MGI Mouse Phenotypes related to Hypothyroidism, Congenital, Nongoitrous, 6:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 immune system MP:0005387 9.28 BCL2L1 CASP3 CXCL13 EGF HPRT1 MARCHF8

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, Pituitary, Bone, Heart

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). 57 6
25670821 2015
2
Clinical phenotype and mutant TRα1. 6 57
22494134 2012
3
A mutation in the thyroid hormone receptor alpha gene. 57 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 Position
1 THRA NM_001190919.1(THRA):c.134G>T (p.Ser45Ile) SNV Pathogenic 29913 rs137853162 GRCh37: 17:38233773-38233773
GRCh38: 17:40077520-40077520
2 THRA NM_001190919.1(THRA):c.1110G>C (p.Lys370Asn) SNV Pathogenic 29914 rs137853163 GRCh37: 17:38245586-38245586
GRCh38: 17:40089333-40089333
3 THRA NM_001190919.1(THRA):c.1110+66C>A SNV Pathogenic 192271 rs876657394 GRCh37: 17:38245652-38245652
GRCh38: 17:40089399-40089399
4 THRA NM_001190919.1(THRA):c.1110+97G>A SNV Pathogenic 192272 rs876657395 GRCh37: 17:38245683-38245683
GRCh38: 17:40089430-40089430
5 THRA NM_001190919.1(THRA):c.1110+83C>G SNV Pathogenic 192273 rs876657396 GRCh37: 17:38245669-38245669
GRCh38: 17:40089416-40089416
6 THRA NM_001190919.1(THRA):c.54-1G>A SNV Pathogenic 561132 rs199530759 GRCh37: 17:38233123-38233123
GRCh38: 17:40076870-40076870
7 THRA NM_199334.5(THRA):c.518A>G (p.Glu173Gly) SNV Likely pathogenic 992628 GRCh37: 17:38241010-38241010
GRCh38: 17:40084757-40084757
8 NR1D1 , THRA NM_021724.5(NR1D1):c.1653G>A (p.Ser551=) SNV Uncertain significance 225490 rs201037953 GRCh37: 17:38249528-38249528
GRCh38: 17:40093275-40093275
9 THRA NM_199334.5(THRA):c.425G>T (p.Arg142Leu) SNV Uncertain significance 803389 rs1598396222 GRCh37: 17:38240917-38240917
GRCh38: 17:40084664-40084664

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

72
# 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 11.35 EGF CASP3 BCL2L1
2 10.95 CASP3 BCL2L1
3 10.83 CASP3 BCL2L1
4 10.65 CASP3 BCL2L1
5 10.52 CASP3 BCL2L1
6 9.77 EGF CASP3

GO Terms for Hypothyroidism, Congenital, Nongoitrous, 6

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

# Name GO ID Score Top Affiliating Genes
1 erythrocyte differentiation GO:0030218 9.26 THRA CASP3
2 neuron apoptotic process GO:0051402 9.16 CASP3 BCL2L1
3 intracellular receptor signaling pathway GO:0030522 8.96 THRA NR1D1
4 extrinsic apoptotic signaling pathway in absence of ligand GO:0097192 8.62 CASP3 BCL2L1

Sources for Hypothyroidism, Congenital, Nongoitrous, 6

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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