GHRHR

growth hormone releasing hormone receptor, the group of Glucagon receptor family

Basic information

Region (hg38): 7:30938669-30993254

Links

ENSG00000106128 ∙ NCBI:2692 ∙ OMIM:139191 ∙ HGNC:4266 ∙ Uniprot:Q02643 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isolated growth hormone deficiency, type 4 (Strong), mode of inheritance: AR
• isolated growth hormone deficiency type IB (Definitive), mode of inheritance: AR
• isolated growth hormone deficiency type IB (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Isolated growth hormone deficiency, type IV	AR	Endocrine	Combined treatment of GH and GNRHa can be effective in increasing final height, even in the case of advanced bone age and pubertal stage, though consideration related to cardiovascular-related treatment effects may be beneficial	Endocrine	8528260; 11443201; 17925337; 19733620; 21274317; 21044116; 22423511; 21816782; 21292919; 22416078

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GHRHR gene.

• not_provided (222 variants)
• Inborn_genetic_diseases (56 variants)
• Isolated_growth_hormone_deficiency_type_IB (38 variants)
• not_specified (29 variants)
• Isolated_growth_hormone_deficiency,_type_4 (23 variants)
• GHRHR-related_disorder (6 variants)
• Pituitary_hormone_deficiency (1 variants)
• Disorder_of_sexual_differentiation (1 variants)
• Isolated_congenital_growth_hormone_deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GHRHR gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000823.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	2		5	70	2	79
missense	5	9	94	14	1	123
nonsense	5	2	1			8
start loss	1		1			2
frameshift	7	2	2			11
splice donor/acceptor (+/-2bp)	3	2	1			6
Total	23	15	104	84	3

Highest pathogenic variant AF is 0.0002051619

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GHRHR	protein_coding	protein_coding	ENST00000326139	13	54586

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.497	262	240	1.09	0.0000148	2733
Missense in Polyphen		88	86.55	1.0168		1110
Synonymous	-1.77	121	98.7	1.23	0.00000643	845
Loss of Function	1.82	15	24.8	0.605	0.00000129	256

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.000163	0.000163
South Asian	0.0000980	0.0000980
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for GRF, coupled to G proteins which activate adenylyl cyclase. Stimulates somatotroph cell growth, growth hormone gene transcription and growth hormone secretion.
• Pathway: Neuroactive ligand-receptor interaction - Homo sapiens (human);GPCRs, Other;GPCRs, Class B Secretin-like;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;Glucagon-type ligand receptors;Class B/2 (Secretin family receptors);GPCR ligand binding;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.223

Intolerance Scores

• loftool: 0.824
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.42

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.223

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: cell surface receptor signaling pathway;G protein-coupled receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;activation of adenylate cyclase activity;lactation;positive regulation of cell population proliferation;determination of adult lifespan;cAMP-mediated signaling;water homeostasis;growth hormone secretion;response to insulin;cellular response to insulin stimulus;regulation of intracellular steroid hormone receptor signaling pathway;positive regulation of multicellular organism growth;hormone metabolic process;positive regulation of insulin-like growth factor receptor signaling pathway;response to estrogen;positive regulation of circadian sleep/wake cycle, non-REM sleep;cell maturation;multicellular organismal reproductive process;regulation of protein metabolic process;response to glucocorticoid;positive regulation of growth hormone secretion;somatotropin secreting cell development;cellular response to glucose stimulus
• Cellular component: nuclear inner membrane;nuclear outer membrane;cytoplasm;plasma membrane;cell surface;integral component of membrane;nuclear matrix;secretory granule;sarcolemma
• Molecular function: G protein-coupled receptor activity;protein binding;G protein-coupled peptide receptor activity;growth hormone-releasing hormone receptor activity;peptide hormone binding;growth factor binding