Table 4.

Intracellular domain (ICD) mutations of GHR relevant to human dwarfism by preventing GHR downstream signaling.

Location	Base Mutation	Defect	Mutation Type	Mechanism	References
Exon 9	removal of exon 9	truncated GHR 1–279	Frameshift	Removal of 26 base pairs of exon 9 does not have direct signaling function, but can form a long–short heterodimer with full-length GHR, inhibiting the STAT5 signal of full-length GHR and may therefore play a significant role in regulating the function of wild-type GHR	[6]
	c.889_911del 1,2	889_911del		Results in an intracellular trafficking of GHR	[50]
	c.899dupC 3			Influences the critical JAK2-binding Box 1 region of the GHR ICD; the duplication predicts early protein termination	[23]
	G920_921insTCTCAAAGATTACA	truncated		Robustly expressed as truncated, fails to activate STAT5B signaling	[63]
	c.945 + 2 T > C	lost Box 1		Excision of exon 9 that can form a long–short heterodimer
Exon 10	c.964dupG	truncated		Robustly expressed as truncated, fails to activate STAT5B signaling
	c.981delC	309delC		Causes the production of 20 novel amino acids (310–329) instead of the wild-type sequence, premature termination at codon 330, and the subsequent deletion of the C terminal portion of the intracellular domain	[52]
	c.1342_1345del	GHR (1–499)		Truncated after Box 1, which results in the isolated failure of STAT 5 signal transduction	[50]
	c.1734delG	1776delG		Lower STAT5-mediated transcriptional activation	[55]
		I544L		Deletes the extracellular domain and forms a nonfunctional receptor, which terminates the signal transmission in advance	[21]

¹ c.: coding sequence; ² del: deletion; ³ dup: duplicate.