Entity Name Entity type Gene Symbol Sources(; separated) Level4 Level3 Level2 Model_Of_Inheritance Phenotypes Omim Orphanet HPO Publications Description Flagged GEL_Status UserRatings_Green_amber_red version ready Mode of pathogenicity EnsemblId(GRch37) EnsemblId(GRch38) HGNC Position Chromosome Position GRCh37 Start Position GRCh37 End Position GRCh38 Start Position GRCh38 End STR Repeated Sequence STR Normal Repeats STR Pathogenic Repeats Region Haploinsufficiency Score Region Triplosensitivity Score Region Required Overlap Percentage Region Variant Type Region Verbose Name DUOX2 gene DUOX2 Eligibility statement prior genetic testing;Expert Review Green;Illumina TruGenome Clinical Sequencing Services;UKGTN Congenital hypothyroidism Endocrinology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Congenital hypothyroidism;Thryoid dyshormonogenesis 6, 607200;permanent congenital hypothyroidism;transient congenital hypothyroidism;eutopic gland-in-situ;goitre;borderline congenital hypothyroidism;iodide organification defect 12110737;24423310;16134168;27525530 (Nicholas et al.,2016) identify a monogenic and digenic basis of disease;27166716 False 3 100;0;0 3.3 False ENSG00000140279 ENSG00000140279 HGNC:13273 DUOXA2 gene DUOXA2 Expert Review Green;Other Congenital hypothyroidism Endocrinology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Thyroid dyshormonogenesis 5, 274900;HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 5;eutopic gland-in-situ;mild congenital hypothyroidism;transient congenital hypothyroidism 18042646;21367925;28100324;26758695;27349010 False 3 100;0;0 3.3 False ENSG00000140274 ENSG00000140274 HGNC:32698 FOXE1 gene FOXE1 Eligibility statement prior genetic testing;Emory Genetics Laboratory;Expert Review Green;UKGTN Congenital hypothyroidism Endocrinology BIALLELIC, autosomal or pseudoautosomal congenital hypothyroidism;Bamforth Lazarus syndrome, 241850 (hypothyroidism);Hypothyroidism, Thyroidal Or Athyroidal, With Spiky Hair And Cleft Palate, 241850;thyroid agenesis;cleft palate;spiky hair;choanal atresia 9697705;20484477;9697704 (mouse model);24219130 (gain-of-function mutation) False 3 100;0;0 3.3 False Other - please provide details in the comments ENSG00000178919 ENSG00000178919 HGNC:3806 GLIS3 gene GLIS3 Expert Review Green;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;UKGTN Congenital hypothyroidism Endocrinology BIALLELIC, autosomal or pseudoautosomal Congenital hypothyroidism;Diabetes mellitus, neonatal, with congenital hypothyroidism, 610199;neonatal non-autoimmune diabetes mellitus;severe congenital hypothyroidism;variable cholestasis;hepatic fibrosis;congenital glaucoma;polycystic kidneys;dysmorphic facies;sensorineural deafness 26259131;16715098 False 3 100;0;0 3.3 False ENSG00000107249 ENSG00000107249 HGNC:28510 GNAS gene GNAS Eligibility statement prior genetic testing;Expert Review Green;NHS GMS Congenital hypothyroidism Endocrinology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Pseudohypoparathyroidism Ia, OMIM:103580;pseudohypoparathyroidism type 1A, MONDO:0007078;Pseudohypoparathyroidism Ib, OMIM:603233;pseudohypoparathyroidism type 1B, MONDO:0011301;Pseudohypoparathyroidism Ic, OMIM:612462;pseudohypoparathyroidism type 1C, MONDO:0012911 17299070; 23412865; 27922245 False 3 0;0;0 3.3 False ENSG00000087460 ENSG00000087460 HGNC:4392 HESX1 gene HESX1 Expert Review Green;Literature Congenital hypothyroidism Endocrinology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Growth hormone deficiency with pituitary anomalies, OMIM:182230;Pituitary hormone deficiency, combined, 5, OMIM:182230;Septooptic dysplasia, OMIM:182230 9620767;11136712;26416826 (2015 review) False 3 100;0;0 3.3 False ENSG00000163666 ENSG00000163666 HGNC:4877 IGSF1 gene IGSF1 Expert Review Green;Literature Congenital hypothyroidism Endocrinology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) central hypothyroidism; hypoprolactinaemia; GH deficiency; macroorchidism; Hypothyroidism, central, and testicular enlargement, 300888 23143598;26840047;27762734;24108313 (reports that a subset of female carriers show central hypothyroidism). False 3 100;0;0 3.3 False ENSG00000147255 ENSG00000147255 HGNC:5948 IRS4 gene IRS4 East of England GLH;Expert Review Green Congenital hypothyroidism Endocrinology X-LINKED: hemizygous mutation in males, biallelic mutations in females Congenital central hypothyroidism 30061370;10644546 False 3 100;0;0 3.3 False ENSG00000133124 ENSG00000133124 HGNC:6128 IYD gene IYD Expert Review Green;Illumina TruGenome Clinical Sequencing Services;Other Congenital hypothyroidism Endocrinology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Thyroid dyshormonogenesis 4, OMIM:274800 18434651;22535972;24629858;18765512 False 3 100;0;0 3.3 False ENSG00000009765 ENSG00000009765 HGNC:21071 LHX3 gene LHX3 Expert Review Green;Literature Congenital hypothyroidism Endocrinology BIALLELIC, autosomal or pseudoautosomal "GH, TSH, LH, FSH, PRL deficiency;limited neck rotation;short cervical spine;sensorineural deafness;anterior pituitary may be normal, hypoplastic or enlarged;Pituitary hormone deficiency, combined, 3, 221750" 10835633;26416826 (2015 review);21249393;18407919 False 3 0;0;0 3.3 False ENSG00000107187 ENSG00000107187 HGNC:6595 LHX4 gene LHX4 Expert Review Green;Literature Congenital hypothyroidism Endocrinology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted GH, TSH, ACTH, variable gonadotrophin deficiencies;cerebellar abnormalities;anterior pituitary hypoplasia;etopic posterior pituitary;Pituitary hormone deficiency, combined, 4, 262700 11567216;26416826 (2015 review);25955177 False 3 100;0;0 3.3 False ENSG00000121454 ENSG00000121454 HGNC:21734 NKX2-1 gene NKX2-1 Expert Review Green;Illumina TruGenome Clinical Sequencing Services;Other;Radboud University Medical Center, Nijmegen;UKGTN Congenital hypothyroidism Endocrinology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Congenital hypothyroidism;Choreoathetosis, hypothyroidism, and neonatal respiratory distress, 610978;Choreoathetosis And Congenital Hypothyroidism With Or Without Pulmonary Dysfunction, 610978;CAHTP;Neurological abnormalities;benign hereditary chorea;neonatal respiratory distress syndrome;recurrent respiratory infections 24714694;11854319 False 3 100;0;0 3.3 False ENSG00000136352 ENSG00000136352 HGNC:11825 OTX2 gene OTX2 Expert Review Green;Literature Congenital hypothyroidism Endocrinology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted GH, TSH, ACTH, LH, FSH deficiency;Anophthalmia Retinal dystrophy;normal or hypoplastic anterior pituitary;ectopic posterior pituitary;Pituitary hormone deficiency, combined, 6, 613986 18628516;26416826 (2015 review) False 3 100;0;0 3.3 False ENSG00000165588 ENSG00000165588 HGNC:8522 PAX8 gene PAX8 Emory Genetics Laboratory;Expert Review Green;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;UKGTN Congenital hypothyroidism Endocrinology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Congenital hypothyroidism;Hypothyroidism, Congenital, Nongoitrous, 2, 218700;Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, 218700;urogenital tract malformations;thyroid hypoplasia;thyroid dysgenesis;eutopic gland-in-situ PMID:23647375;PMID:9590296 False 3 100;0;0 3.3 False ENSG00000125618 ENSG00000125618 HGNC:8622 POU1F1 gene POU1F1 Expert Review Green;Other Congenital hypothyroidism Endocrinology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Pituitary hormone deficiency, combined or isolated, 1, OMIM:613038;Congenital hypothyroidism 26416826;11297581; 16060904 False 3 100;0;0 3.3 False Other - please provide details in the comments ENSG00000064835 ENSG00000064835 HGNC:9210 PRKAR1A gene PRKAR1A Expert Review Green;Literature Congenital hypothyroidism Endocrinology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Acrodysostosis, mild hormone resistance (TSH, PTH, GPCR-cAMP signalling hormones;Acrodysostosis 1, with or without hormone resistance, 101800 21651393;22464250 False 3 100;0;0 3.3 False Other - please provide details in the comments ENSG00000108946 ENSG00000108946 HGNC:9388 PROP1 gene PROP1 Expert Review Green;Literature Congenital hypothyroidism Endocrinology BIALLELIC, autosomal or pseudoautosomal GH, TSH, LH, FSH, PRL deficiency with variable age of onset, evolving ACTH deficiency;Commonest cause of combined pituitary hormone deficit without extra pituitary manifestations;Hypoplastic or normal anterior pituitary although there have been reports of an enlarged anterior pituitary at initial scanning in childhood with spontaneous involution over time;Pituitary hormone deficiency, combined, 2, 262600 9768691;15126542;15472175;26416826 (2015 review);23652424;16984240 False 3 100;0;0 3.3 False ENSG00000175325 ENSG00000175325 HGNC:9455 SECISBP2 gene SECISBP2 Expert Review Green Congenital hypothyroidism Endocrinology BIALLELIC, autosomal or pseudoautosomal Short stature-delayed bone age due to thyroid hormone metabolism deficiency;Selenocysteine insertion sequence binding protein 2 (SBP2) defect;Abnormal thyroid hormone metabolism;Thyroid hormone metabolism, abnormal, 609698;THYROID HORMONE METABOLISM, ABNORMAL 24629861;22986150;Diversity Selenium Functions in Health and Disease, Edited by Regina Brigelius-Flohe and Helmut Sies, Chapter 16. Mutations in SECISBP2. Erik Schoenmakers, Carla Moran, Nadia Schoenmakers and Krishna Chatterjee. CRC Press 2015. Pages 343 376. Print ISBN: 978-1-4822-5126-5. eBook ISBN: 978-1-4822-5127-2. DOI: 10.1201/b18810-23;20501692;19602558;22247018;16228000;21084748 False 3 0;0;0 3.3 False ENSG00000187742 ENSG00000187742 HGNC:30972 SLC16A2 gene SLC16A2 Expert Review Green Congenital hypothyroidism Endocrinology X-LINKED: hemizygous mutation in males, biallelic mutations in females Allan-Herndon-Dudley syndrome, OMIM:300523 24847459 False 3 0;0;0 3.3 False ENSG00000147100 ENSG00000147100 HGNC:10923 SLC26A4 gene SLC26A4 Eligibility statement prior genetic testing;Expert Review Green;Other Congenital hypothyroidism Endocrinology BIALLELIC, autosomal or pseudoautosomal Pendred syndrome, 274600 (congenital deafness and thyroid goitre);Sensorineural deafness;enlarged vestibular aqueduct;Mondini defect;partial iodide organification defect;goitre;mild hypothyroidism 9398842;11932316 False 3 100;0;0 3.3 False ENSG00000091137 ENSG00000091137 HGNC:8818 SLC26A7 gene SLC26A7 East of England GLH;Expert Review Green Congenital hypothyroidism Endocrinology BIALLELIC, autosomal or pseudoautosomal Primary congenital hypothyroidism (dyshormonogenesis) 29546359;30333321 False 3 100;0;0 3.3 False ENSG00000147606 ENSG00000147606 HGNC:14467 SLC5A5 gene SLC5A5 Expert Review Green;Other Congenital hypothyroidism Endocrinology BIALLELIC, autosomal or pseudoautosomal Thyroid dyshormonogenesis 1, 274400;HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 1;Apparent athyreosis on nuclear medicine scan;goitre;childhood onset hypothyroidism 9171822;16418213 False 3 100;0;0 3.3 False ENSG00000105641 ENSG00000105641 HGNC:11040 TBL1X gene TBL1X Expert Review Green;Literature Congenital hypothyroidism Endocrinology X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) isolated mild-moderate central hypothyroidism;Hypothyroidism, congenital, nongoitrous, 8, 301033 27603907;30591955 False 3 100;0;0 3.3 False ENSG00000101849 ENSG00000101849 HGNC:11585 TG gene TG Eligibility statement prior genetic testing;Expert Review Green;UKGTN Congenital hypothyroidism Endocrinology BIALLELIC, autosomal or pseudoautosomal Congenital hypothyroidism;Thyroid dyshormonogenesis 3, 274700;TDH3;low thyroglobulin, goitre 23164529;27525530 (Nicholas et al.,2016) identify a monogenic and polygenic basis of disease. False 3 100;0;0 3.3 False ENSG00000042832 ENSG00000042832 HGNC:11764 THRA gene THRA Expert Review Green;Radboud University Medical Center, Nijmegen;UKGTN Congenital hypothyroidism Endocrinology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Congenital hypothyroidism or thyroid agenesis;Hypothyroidism, Congenital, Nongoitrous, 6, 614450;Hypothyroidism, congenital, nongoitrous, 6, 614450;Resistance to thyroid hormone;skeletal dysplasia;growth retardation;macrocephaly;neurodevelopmental delay;constipation;delayed dentition;macrocytic anaemia 22168587;23940126;24847459;27381958;22168587;22494134;23940126;2567082;27144938 False 3 0;0;100 3.3 False ENSG00000126351 ENSG00000126351 HGNC:11796 THRB gene THRB Expert Review Green Congenital hypothyroidism Endocrinology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Resistance to thyroid hormone (RTH);THYROID HORMONE UNRESPONSIVENESS;145650;REFETOFF SYNDROME;PRTH;Thyroid hormone resistance, autosomal recessive, 274300;Refetoff syndrome;THYROID HORMONE RESISTANCE, SELECTIVE PITUITARY;thyroid hormone unresponsiveness, generalized RTH, RTH beta;Thyroid hormone resistance, 188570;THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL DOMINANT;THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL RECESSIVE;Thyroid Hormone Resistance (monoallelic);Thyroid hormone resistance, selective pituitary, 145650;HYPERTHYROIDISM, FAMILIAL, DUE TO INAPPROPRIATE THYROTROPIN SECRETION;GRTH;Thyroid Hormone Resistance, Selective Pituitary;THYROID HORMONE UNRESPONSIVENESS HYPERTHYROXINEMIA, FAMILIAL EUTHYROID, SECONDARY TO PITUITARY AND PERIPHERAL RESISTANCE TO THYROID HORMONES 24847459 False 3 0;0;0 3.3 False ENSG00000151090 ENSG00000151090 HGNC:11799 TPO gene TPO Eligibility statement prior genetic testing;Expert Review Green;Illumina TruGenome Clinical Sequencing Services;UKGTN Congenital hypothyroidism Endocrinology BIALLELIC, autosomal or pseudoautosomal Thyroid dyshormonogenesis 2A, OMIM:274500 12938097;8027236;8964831;11061528;27525530 (Nicholas et al.,2016) identify a monogenic basis of disease;27166716;39890415 False 3 100;0;0 3.3 False ENSG00000115705 ENSG00000115705 HGNC:12015 TRHR gene TRHR Expert Review Green;Literature Congenital hypothyroidism Endocrinology BIALLELIC, autosomal or pseudoautosomal mild-moderate isolated central hypothyroidism;absent TSH and prolactin response to TRH;Thyrotropin-releasing hormone resistance, generalized PMID: 9141550; PMID: 19213692 False 3 100;0;0 3.3 False ENSG00000174417 ENSG00000174417 HGNC:12299 TSHB gene TSHB Expert Review Green;Illumina TruGenome Clinical Sequencing Services;Other Congenital hypothyroidism Endocrinology BIALLELIC, autosomal or pseudoautosomal Congenital hypothyroidism;Hypothryoidism, congenital, nongoitrous 4, 275100;severe isolated central hypothyroidism 2792087;27362444 False 3 100;0;0 3.3 False ENSG00000134200 ENSG00000134200 HGNC:12372 TSHR gene TSHR Eligibility statement prior genetic testing;Expert Review Green;Illumina TruGenome Clinical Sequencing Services;Radboud University Medical Center, Nijmegen;UKGTN Congenital hypothyroidism Endocrinology BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Congenital hypothyroidism;Hypothyroidism, Congenital, Nongoitrous, 1, 275200;Hypothyroidism, congenital, nongoitrous, 1 275200;TSH resistance;thyroid hypoplasia;subclinical hypothyroidism;thyroid dysgenesis;eutopic gland-in-situ;compensated hypothryoidism 7528344;22876533;PMID:17526952 (Kanda et al., 2006) examine Japanese patients homozygous and heterozygous for the R450H mutation in the TSHR gene. Homozygous subjects displayed mild hypothyroidism/ Heterozygous patients also demonstrated hypothyroidism, but less severe than that of homozygous subjects.;PMID:14725684 (Park et al. 2004) suggest that heterozygosity for an inactivating TSHR mutation may be associated with compensated hypothyroidism and thyroid hypoplasia;16060907 (Camilot et al., 2005 report subclinical hypothyroid subjects with heterozygous substitutions;27525530 (Nicholas et al.,2016) identify a monogenic basis of disease. False 3 100;0;0 3.3 False ENSG00000165409 ENSG00000165409 HGNC:12373 CDCA8 gene CDCA8 Expert Review;Expert Review Amber;Literature;NHS GMS Congenital hypothyroidism Endocrinology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Congenital hypothyroidism;thyroid dysgenesis;No OMIM number 28025328;29546359 False 2 0;100;0 3.3 False Other ENSG00000134690 ENSG00000134690 HGNC:14629 NKX2-5 gene NKX2-5 Expert Review Amber;Other;Radboud University Medical Center, Nijmegen Congenital hypothyroidism Endocrinology MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Hypothyroidism, congenital nongoitrous, 5, 225250;thyrioid ectopy, thyroid agenesis, congenital heart disease 16418214 False 2 0;0;100 3.3 False Other - please provide details in the comments ENSG00000183072 ENSG00000183072 HGNC:2488 TUBB1 gene TUBB1 East of England GLH;Expert Review Amber Congenital hypothyroidism Endocrinology BOTH monoallelic and biallelic, autosomal or pseudoautosomal Primary congenital hypothyroidism, thyroid dysgenesis, macroplatelets 30446499 False 2 0;100;0 3.3 False ENSG00000101162 ENSG00000101162 HGNC:16257 ISCA-37478-Loss region Expert Review Amber;ClinGen Congenital hypothyroidism Endocrinology MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown microcephaly;Developmental delay, muscle weakness;Mental retardation;Angelman syndrome;176270;Prader-Willi syndrome;105830 22045295;7611294 False 2 0;0;0 3.3 False 15 23465365 28134728 3 60 cnv_loss 15q11q13 recurrent (PWS/AS) region (BP2-BP3, Class 2) Loss