GNRHR

gonadotropin releasing hormone receptor, the group of Gonadotropin releasing hormone receptors

Basic information

Region (hg38): 4:67737117-67754388

Previous symbols: [ "GRHR" ]

Links

ENSG00000109163 ∙ NCBI:2798 ∙ OMIM:138850 ∙ HGNC:4421 ∙ Uniprot:P30968 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypogonadotropic hypogonadism 7 with or without anosmia (Strong), mode of inheritance: AR
• hypogonadotropic hypogonadism (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypogonadotropic hypogonadism 7 with or without anosmia; Hypogonadotropic hypogonadism 23 with or without anosmia	AD/AR/Digenic	Endocrine	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	Endocrine; Genitourinary	13061573; 9371856; 10690855; 11397842; 17235395; 20301455; 20301509; 22035731; 22724017
Digenic inheritance (with FGFR1) has been reported

ClinVar

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

• Hypogonadotropic hypogonadism 7 with or without anosmia (85 variants)
• not provided (44 variants)
• Isolated GnRH Deficiency (9 variants)
• Inborn genetic diseases (5 variants)
• not specified (3 variants)
• Hypogonadotropic hypogonadism (2 variants)
• Delayed puberty (1 variants)
• GNRHR-related condition (1 variants)
• Gonadotropin deficiency (1 variants)
• Amenorrhea (1 variants)
• Isolated congenital hypogonadotropic hypogonadism (1 variants)
• Infertility disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNRHR gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	4	2	9
missense	10	11	23	1		45
nonsense	1					1
start loss			1			1
frameshift	1	1				2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			48	4	12	64
Total	12	12	75	9	14

Highest pathogenic variant AF is 0.000197

Variants in GNRHR

This is a list of pathogenic ClinVar variants found in the GNRHR region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-67737404-A-G		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 13, 2018)
4-67737469-A-G		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 13, 2018)
4-67737561-T-C		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 13, 2018)
4-67737678-A-G		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 13, 2018)
4-67737708-T-C		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 13, 2018)
4-67737713-A-G		Hypogonadotropic hypogonadism 7 with or without anosmia	Likely benign (Jan 12, 2018)
4-67737732-G-A		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 13, 2018)
4-67737817-C-A		Hypogonadotropic hypogonadism 7 with or without anosmia	Benign (Mar 06, 2018)
4-67737892-G-A		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 13, 2018)
4-67737984-C-T		Hypogonadotropic hypogonadism 7 with or without anosmia	Benign (Jan 12, 2018)
4-67738039-A-G		Hypogonadotropic hypogonadism 7 with or without anosmia	Likely benign (Jan 13, 2018)
4-67738152-T-A		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 13, 2018)
4-67738232-A-G		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 13, 2018)
4-67738236-A-G		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 13, 2018)
4-67738284-C-T		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 13, 2018)
4-67738314-C-T		Hypogonadotropic hypogonadism 7 with or without anosmia	Benign (Jan 13, 2018)
4-67738315-T-C		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 12, 2018)
4-67738425-C-T		Hypogonadotropic hypogonadism 7 with or without anosmia	Benign (Jan 12, 2018)
4-67738447-G-GT		Isolated GnRH Deficiency	Uncertain significance (Jun 14, 2016)
4-67738448-T-TA		Isolated GnRH Deficiency	Uncertain significance (Jun 14, 2016)
4-67738496-A-G		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 13, 2018)
4-67738532-G-A		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 12, 2018)
4-67738588-G-T		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 13, 2018)
4-67738589-A-C		Hypogonadotropic hypogonadism 7 with or without anosmia	Benign (Jan 13, 2018)
4-67738683-T-C		Hypogonadotropic hypogonadism 7 with or without anosmia	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNRHR	protein_coding	protein_coding	ENST00000226413	3	15033

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0676	0.920	125730	0	10	125740	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.301	155	166	0.934	0.00000821	2164
Missense in Polyphen		63	67.252	0.93678		855
Synonymous	-0.0675	64	63.3	1.01	0.00000317	638
Loss of Function	2.18	4	12.2	0.328	6.14e-7	141

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000218	0.000213
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle- stimulating hormone (FSH). This receptor mediates its action by association with G-proteins that activate a phosphatidylinositol- calcium second messenger system. Isoform 2 may act as an inhibitor of GnRH-R signaling.
• Pathway: GnRH signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);GPCRs, Other;Peptide GPCRs;Signaling by GPCR;Signal Transduction;Hormone ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.236

Intolerance Scores

• loftool: 0.492
• rvis_EVS: -0.12
• rvis_percentile_EVS: 45.13

Haploinsufficiency Scores

• pHI: 0.441
• hipred: N
• hipred_score: 0.144
• ghis: 0.392

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.215

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gnrhr
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); normal phenotype; reproductive system phenotype; growth/size/body region phenotype; digestive/alimentary phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;multicellular organism development;cellular response to hormone stimulus;cellular response to gonadotropin-releasing hormone
• Cellular component: plasma membrane;integral component of plasma membrane;membrane
• Molecular function: gonadotropin-releasing hormone receptor activity