Molecule Information

General Information of the Molecule (ID: Mol01926)

• Name: Paired box 8 (PAX8) ,Homo sapiens
• Synonyms: PAX8
• Molecule Type: Protein
• Gene Name: PAX8
• Gene ID: 7849
• Location: chr2:113,215,997-113,278,921[-]
• Sequence:
  MPHNSIRSGHGGLNQLGGAFVNGRPLPEVVRQRIVDLAHQGVRPCDISRQLRVSHGCVSK
  ILGRYYETGSIRPGVIGGSKPKVATPKVVEKIGDYKRQNPTMFAWEIRDRLLAEGVCDND
  TVPSVSSINRIIRTKVQQPFNLPMDSCVATKSLSPGHTLIPSSAVTPPESPQSDSLGSTY
  SINGLLGIAQPGSDKRKMDDSDQDSCRLSIDSQSSSSGPRKHLRTDAFSQHHLEPLECPF
  ERQHYPEAYASPSHTKGEQGLYPLPLLNSTLDDGKATLTPSNTPLGRNLSTHQTYPVVAD
  PHSPFAIKQETPEVSSSSSTPSSLSSSAFLDLQQVGSGVPPFNAFPHAASVYGQFTGQAL
  LSGREMVGPTLPGYPPHIPTSGQGSYASSAIAGMVAGSEYSGNAYGHTPYSSYSEAWRFP
  NSSLLSSPYYYSSTSRPSAPPTTATAFDHL
• Function: Transcription factor for the thyroid-specific expression of the genes exclusively expressed in the thyroid cell type, maintaining the functional differentiation of such cells.
• Uniprot ID: PAX8_HUMAN
• Ensembl ID: ENSG00000125618
• HGNC ID: HGNC:8622

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Investigative Drug(s) 1 drug(s) in total

Thyrotropin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Subclinical hypothyroidism [1]

• Resistant Disease: Subclinical hypothyroidism [ICD-11: 5A00.22]
• Resistant Drug: Thyrotropin
• Molecule Alteration: Missense mutation; p.L16P
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: PAX8 mutations are not a relevant cause of sporadic thyroid ectopy or genuine agenesis but found in a minority of cases (e.g. 1/28 German, 1/16 Chinese) within the normotopic hypoplasia subgroup. More generally, heterozygous PAX8 LOF mutations have to be considered as another cause of RTSH that is clinically and by thyroid function tests indistinguishable from that caused by TSHR mutations. The clinical severity can thus range from subclinical hypothyroidism with normal-sized gland to overt hypothyroidism with severe thyroid gland hypoplasia.

Disease Class: Subclinical hypothyroidism [1]

• Resistant Disease: Subclinical hypothyroidism [ICD-11: 5A00.22]
• Resistant Drug: Thyrotropin
• Molecule Alteration: Missense mutation; p.F20S
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: PAX8 mutations are not a relevant cause of sporadic thyroid ectopy or genuine agenesis but found in a minority of cases (e.g. 1/28 German, 1/16 Chinese) within the normotopic hypoplasia subgroup. More generally, heterozygous PAX8 LOF mutations have to be considered as another cause of RTSH that is clinically and by thyroid function tests indistinguishable from that caused by TSHR mutations. The clinical severity can thus range from subclinical hypothyroidism with normal-sized gland to overt hypothyroidism with severe thyroid gland hypoplasia.

Disease Class: Subclinical hypothyroidism [1]

• Resistant Disease: Subclinical hypothyroidism [ICD-11: 5A00.22]
• Resistant Drug: Thyrotropin
• Molecule Alteration: Missense mutation; p.R133Q
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: PAX8 mutations are not a relevant cause of sporadic thyroid ectopy or genuine agenesis but found in a minority of cases (e.g. 1/28 German, 1/16 Chinese) within the normotopic hypoplasia subgroup. More generally, heterozygous PAX8 LOF mutations have to be considered as another cause of RTSH that is clinically and by thyroid function tests indistinguishable from that caused by TSHR mutations. The clinical severity can thus range from subclinical hypothyroidism with normal-sized gland to overt hypothyroidism with severe thyroid gland hypoplasia.

Disease Class: Congenital hypothyroidism [1]

• Resistant Disease: Congenital hypothyroidism [ICD-11: 5A00.0]
• Resistant Drug: Thyrotropin
• Molecule Alteration: Missense mutation; p.L16P
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: PAX8 mutations are not a relevant cause of sporadic thyroid ectopy or genuine agenesis but found in a minority of cases (e.g. 1/28 German, 1/16 Chinese) within the normotopic hypoplasia subgroup. More generally, heterozygous PAX8 LOF mutations have to be considered as another cause of RTSH that is clinically and by thyroid function tests indistinguishable from that caused by TSHR mutations. The clinical severity can thus range from subclinical hypothyroidism with normal-sized gland to overt hypothyroidism with severe thyroid gland hypoplasia.

Disease Class: Congenital hypothyroidism [1]

• Resistant Disease: Congenital hypothyroidism [ICD-11: 5A00.0]
• Resistant Drug: Thyrotropin
• Molecule Alteration: Missense mutation; p.F20S
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: PAX8 mutations are not a relevant cause of sporadic thyroid ectopy or genuine agenesis but found in a minority of cases (e.g. 1/28 German, 1/16 Chinese) within the normotopic hypoplasia subgroup. More generally, heterozygous PAX8 LOF mutations have to be considered as another cause of RTSH that is clinically and by thyroid function tests indistinguishable from that caused by TSHR mutations. The clinical severity can thus range from subclinical hypothyroidism with normal-sized gland to overt hypothyroidism with severe thyroid gland hypoplasia.

Disease Class: Congenital hypothyroidism [1]

• Resistant Disease: Congenital hypothyroidism [ICD-11: 5A00.0]
• Resistant Drug: Thyrotropin
• Molecule Alteration: Missense mutation; p.R133Q
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: PAX8 mutations are not a relevant cause of sporadic thyroid ectopy or genuine agenesis but found in a minority of cases (e.g. 1/28 German, 1/16 Chinese) within the normotopic hypoplasia subgroup. More generally, heterozygous PAX8 LOF mutations have to be considered as another cause of RTSH that is clinically and by thyroid function tests indistinguishable from that caused by TSHR mutations. The clinical severity can thus range from subclinical hypothyroidism with normal-sized gland to overt hypothyroidism with severe thyroid gland hypoplasia.

References

• Ref 1: Resistance to thyrotropin .Best Pract Res Clin Endocrinol Metab. 2017 Mar;31(2):183-194. doi: 10.1016/j.beem.2017.03.004. Epub 2017 Mar 30. 10.1016/j.beem.2017.03.004