Table 2.

Mutations in the GHR dimerization domain relevant to human dwarfism.

Location	Base Mutation	Defect	Mutation Type	Mechanism	References
Exon 6		P131Q	Missense		[52]
	c.476 T > A 1	L141X	Nonsense	Introduces a premature termination codon that leads to a truncated non-functioning receptor	[50]
	c.484 G > A	V144I		Associated with idiopathic short stature	[13]
	c.484 G > T	V144F			[46]
	c.485 T > A	V144D	Missense		[52]
	c.485 T > C	V144A			[46]
	c.504 T > G	H150Q	Missense		[44]
	c.508 G > C	D152H	Missense	Disrupts the expression, dimerization, and signaling of GHR	[52]
		D152G	Missense		[57]
	c.512 T > C	I153T	Missense	Mainly affects intracellular trafficking and binding affinity of the receptor	[50,58]
	c.515 A > C	Q154P	Missense	Leads to severe defects both at the cell surface and in total particulate membrane fractions
	c.518 T > G	V155G	Missense	Affects intracellular trafficking and binding affinity of GHR
	c.524 G > A	W157X	Nonsense	Produces a truncated GHR, lacking part of exons 6 and 7–10, defective in both cell membrane anchoring and GH binding	[41]
	c.535 C > T	R161C	Missense	Causes low serum GHBP concentrations	[52]
	c.558 A > G	G168G		Deletes the ECD and forms a nonfunctional receptor that terminates the signal transmission in advance	[10]
	c.559 T > C	W169R		Since Trp169 plays an important role in the stabilization of the GH–GHR interaction, this mutation in chain 1, which binds to GH site 1, showed a decreased affinity for GH, affecting the interaction in the complex	[8]
	c.591 C > T	R179C			[48]
	c.594 G > T	E180X	Nonsense	Deletes the ECD and forms a nonfunctional receptor, which terminates the signal transmission in advance	[21,44]
	c.594 A > G	E180sp 2	Splice site	Causes deletion of residues 181–188 in the dimerization functional region	[44]
	c.601 G > T	E183X	Nonsense		[50]
	del 3	deletion of exon 6	Frameshift	Results in a deletion of a large portion of the ECD of GHR	[50]
Exon 7		M207 fs. X8	Deletion	Results in premature termination, which decreases GH binding affinity	[49]
	c.677 A > G	Y208C	Missense	Prevents normal interactions in the membrane proximal domain of the extracellular part of the receptor	[50]
	c.685 C > G	R211G	Missense		[52]
	c.703 C > T	R217X	Nonsense	Deletes the ECD and forms a nonfunctional receptor, which terminates the signal transmission in advance	[21]
	c.723 C > T	G223G	Splice site	May interfere with GH binding activity	[41]
	c.724 G > T	G224X	Nonsense		[52]
	656 C > T	p.S219L 4			[59]
	c.731 G > T	S226I	Missense	Occurs in WSXWS-like motif of GHR causing GH insensitivity	[60]
		R229H			[23]
	a nucleotide del	del203AT or TA	Frameshift	Results in high GH levels and low levels of IGF-1, IGF-2, IGFBP 3, and GHBP	[61]
	c.743_744 del AT	230delAT	Nonsense		[52]
	c.766 C > T	G236sp	Splice site	Activates the cryptic splice donor site within exon 7
	c.784 G > C	D244N	Missense	Induces functional loss of the native intron 7 donor splice site, leading to a frame shift and predicted early protein termination	[62]
Exon 8	c.875 G > C	R274T	Splice site	Generates a truncated protein	[52]
		S473S			[37]

¹ c.: coding sequence; ² sp: splice; ³ del: deletion; ⁴ p.: pre-peptide.