Table 1.
Details of the 38 Genes Studied and Their Associated Endocrine Disorders
| Gene | Disorder(s) Associated With Germline Mutation | Mutation Type | Inheritance Pattern | Canonical Transcript |
|---|---|---|---|---|
| AIP | Familial isolated pituitary adenoma | Het (LOF, MS) | AD (RP) | ENST00000279146 |
| Sporadic pituitary adenomas | Het (LOF, MS) | Sporadic | ||
| AP2S1 | Familial hypocalciuric hypercalcemia | Het (MS) | AD | ENST00000263270 |
| ARMC5 | Familial macronodular adrenal hyperplasia | Het (MS) | AD (RP) | ENST00000268314 |
| Sporadic macronodular adrenal hyperplasia | Het (MS) | Sporadic | ||
| CASR | Familial hypocalciuric hypercalcemia | Het (MS) | AD | ENST00000498619 |
| Familial isolated hyperparathyroidism | Het (MS) | AD | ||
| Autosomal dominant hypocalcemia | Het (MS) | AD | ||
| CDC73 | Hyperparathyroidism-jaw tumor syndrome | Het (LOF, MS) | AD | ENST00000367435 |
| Sporadic parathyroid carcinoma | Het (LOF, MS) | Sporadic | ||
| CDKN1Aa | Sporadic parathyroid adenoma | Het (MS) | Sporadic | ENST00000405375 |
| CDKN1B | Multiple endocrine neoplasia type 4 | Het (LOF, MS) | AD | ENST00000228872 |
| Sporadic parathyroid and pituitary adenoma | Het (MS) | Sporadic | ||
| CDKN2Ba | Sporadic parathyroid adenoma | Het (MS) | Sporadic | ENST00000276925 |
| CDKN2Ca | Sporadic parathyroid adenoma | Het (MS) | Sporadic | ENST00000262662 |
| CHD7 | Hypogonadotropic hypogonadism type 5/CHARGE | Het (LOF, MS) | AD (RP) | ENST00000423902 |
| EGLN1 | Sporadic pheochromocytoma/paraganglioma | Het (MS) | Sporadic | ENST00000366641 |
| EPAS1 | Sporadic pheochromocytoma/paraganglioma | Het (MS) | Sporadic | ENST00000263734 |
| FGF23 | Autosomal dominant hypophosphatemic rickets | Het (MS) | AD | ENST00000237837 |
| FH | Hereditary leiomyomatosis/renal cell carcinoma | Het (LOF, MS) | AD | ENST00000366560 |
| Sporadic pheochromocytoma/paraganglioma | Het (MS) | Sporadic | ||
| GATA3 | Hypoparathyroidism/deafness/renal dysplasia | Het (LOF, MS) | AD | ENST00000379328 |
| GHR | Laron dwarfism | Homo (LOF, MS) | AR | ENST00000230882 |
| Idiopathic short stature | Hetb (LOF, MS) | AD (?) | ||
| GNA11 | Familial hypocalciuric hypercalcemia | Het (MS) | AD | ENST00000078429 |
| Autosomal dominant hypocalcemia | Het (MS) | AD | ||
| GNAS | Pseudohypoparathyroidism type 1a | Het (LOF, MS) | ADc | ENST00000371100 |
| GPR101a | Sporadic acromegaly | Het/Hemi (MS) | Sporadic | ENST00000298110 |
| KAL1 | Hypogonadotropic hypogonadism type 1 | Hemi (LOF, MS) | XLD | ENST00000262648 |
| KCNJ5 | Familial hypertension | Het (MS) | AD | ENST00000529694 |
| KIF1B | Familial pheochromocytoma/paraganglioma | Het (MS) | AD | ENST00000263934 |
| Sporadic pheochromocytoma/paraganglioma | Het (MS) | Sporadic | ||
| MAX | Familial pheochromocytoma/paraganglioma | Het (LOF, MS) | AD (RP) | ENST00000358664 |
| Sporadic pheochromocytoma/paraganglioma | Het (LOF, MS) | Sporadic | ||
| MEN1 | Multiple endocrine neoplasia type 1 | Het (LOF, MS) | AD | ENST00000337652 |
| NF1 | Neurofibromatosis | Het (LOF, MS) | AD | ENST00000358273 |
| PHEX | X-linked hypophosphatemic rickets | Het/Hemi (LOF, MS) | XLD | ENST00000379374 |
| PRKAR1A | Carney complex | Het (LOF, MS) | AD | ENST00000589228 |
| PRLR | Hereditary hyperprolactinemia | Het (MS) | AD | ENST00000382002 |
| RET | Multiple endocrine neoplasia type 2 | Het (MS) | AD | ENST00000355710 |
| Familial medullary thyroid cancer | Het (MS) | AD | ||
| SDHA | Familial pheochromocytoma/paraganglioma | Het (LOF, MS) | AD (RP) | ENST00000264932 |
| Sporadic pheochromocytoma/paraganglioma | Het (LOF, MS) | Sporadic | ||
| SDHAF2 | Familial pheochromocytoma/paraganglioma | Het (MS) | AD (RP) | ENST00000301761 |
| Sporadic pheochromocytoma/paraganglioma | Het (LOF) | Sporadic | ||
| SDHB | Familial pheochromocytoma/paraganglioma | Het (LOF, MS) | AD (RP) | ENST00000375499 |
| Sporadic pheochromocytoma/paraganglioma | Het (LOF, MS) | Sporadic | ||
| SDHC | Sporadic pheochromocytoma/paraganglioma | Het (LOF, MS) | Sporadic | ENST00000367975 |
| SDHD | Familial pheochromocytoma/paraganglioma | Het (LOF, MS) | AD (RP)c | ENST00000375549 |
| Sporadic pheochromocytoma/paraganglioma | Het (LOF, MS) | Sporadic | ||
| THRA_1d | Thyroid hormone resistance | Het (LOF,d MS) | AD | ENST00000450525 |
| THRA_2d | Thyroid hormone resistance | Het (MS) | AD | ENST00000264637 |
| THRB | Thyroid hormone resistance | Het (LOF, MS) | AD | ENST00000396671 |
| TMEM127 | Familial pheochromocytoma/paraganglioma | Het (LOF, MS) | AD (RP) | ENST00000258439 |
| Sporadic pheochromocytoma/paraganglioma | Het (LOF, MS) | Sporadic | ||
| VHL | Von Hippel-Lindau (VHL) | Het (LOF, MS) | AD | ENST00000256474 |
| Sporadic pheochromocytoma/paraganglioma | Het (LOF, MS) | Sporadic |
Abbreviations: AD, autosomal dominant; AR, autosomal recessive; Hemi, hemizygous; Het, heterozygous; MS, missense; RP, reduced penetrance; XLD, X-linked dominant.
a
Genes reported to be associated with endocrine disease, although evidence supporting pathogenicity may be limited.
b
Evidence supporting heterozygous GHR mutations in idiopathic short stature remains unclear.
c
Diseases associated with genomic imprinting.
d
THRA_1 refers to THRA isoform 1 encoded by the noncanonical transcript ENST00000450525. Disease-associated nonsense and missense mutations in final exon of isoform 1 are reported. THRA_2 refers to THRA isoform 2 encoded by the canonical transcript (ENST00000450525), in which a missense mutation, also present in isoform 1, has been reported.