KISS1R

KISS1 receptor, the group of Peptide receptors

Basic information

Region (hg38): 19:917286-921005

Previous symbols: [ "GPR54" ]

Links

ENSG00000116014 ∙ NCBI:84634 ∙ OMIM:604161 ∙ HGNC:4510 ∙ Uniprot:Q969F8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• centra precocious puberty 1 (Limited), mode of inheritance: AD
• hypogonadotropic hypogonadism 8 with or without anosmia (Definitive), mode of inheritance: AR
• hypogonadotropic hypogonadism (Supportive), mode of inheritance: AD
• hypogonadotropic hypogonadism 8 with or without anosmia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypogonadotropic hypogonadism 8 with or without anosmia	AR	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; Neurologic	11600530; 12788910; 12788881; 14573733; 18272894; 20301509
In Precocious puberty, treatment with gonadotropin-releasing hormone receptor analogs/LHRH agonists can be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KISS1R gene.

• not provided (79 variants)
• Inborn genetic diseases (21 variants)
• not specified (8 variants)
• Hypogonadotropic hypogonadism 8 with or without anosmia (5 variants)
• Centra precocious puberty 1 (3 variants)
• Hypogonadotropic hypogonadism 8 without anosmia (2 variants)
• Hypogonadotropic hypogonadism (1 variants)
• Hypogonadotropic hypogonadism 8 with or without anosmia;Centra precocious puberty 1 (1 variants)
• Centra precocious puberty 1;Hypogonadotropic hypogonadism 8 with or without anosmia (1 variants)
• Abnormality of the genitourinary system (1 variants)
• Pituitary stalk interruption syndrome (1 variants)
• Bilateral cryptorchidism;Microphallus (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KISS1R 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				16	4	20
missense		2	37	2	2	43
nonsense		1	1			2
start loss						0
frameshift	2	1	2			5
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region			3	2		5
non coding			1	10	11	22
Total	2	6	41	28	17

Highest pathogenic variant AF is 0.0000788

Variants in KISS1R

This is a list of pathogenic ClinVar variants found in the KISS1R region.

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

Position	Type	Phenotype	Significance	ClinVar
19-917380-C-T			Benign (Sep 22, 2018)
19-917499-G-A		KISS1R-related disorder	Likely benign (Mar 10, 2023)
19-917511-C-T		KISS1R-related disorder	Benign (Dec 09, 2023)
19-917520-G-A		Centra precocious puberty 1;Hypogonadotropic hypogonadism 8 with or without anosmia • KISS1R-related disorder	Benign/Likely benign (Apr 10, 2023)
19-917526-A-G		not specified • Hypogonadotropic hypogonadism 8 with or without anosmia	Benign (Jan 29, 2024)
19-917537-C-T		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
19-917543-G-A		Inborn genetic diseases	Uncertain significance (Dec 02, 2022)
19-917549-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jul 06, 2022)
19-917570-C-T		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
19-917575-T-C			Uncertain significance (Apr 27, 2022)
19-917584-A-C		Hypogonadotropic hypogonadism 8 with or without anosmia	Uncertain significance (-)
19-917614-C-T			Uncertain significance (Nov 01, 2022)
19-917616-G-T			Likely benign (May 25, 2018)
19-917653-GC-G			Likely pathogenic (Dec 14, 2019)
19-917659-A-T		Inborn genetic diseases	Uncertain significance (May 24, 2023)
19-917666-TG-T			not provided (-)
19-917669-G-A		Inborn genetic diseases	Uncertain significance (Apr 21, 2022)
19-917718-G-A		KISS1R-related disorder	Likely benign (Jan 25, 2024)
19-917735-A-G		Hypogonadotropic hypogonadism 8 with or without anosmia	Uncertain significance (May 15, 2018)
19-917740-T-C		Inborn genetic diseases	Uncertain significance (Jun 30, 2022)
19-917874-C-T			Benign (Jun 26, 2018)
19-917929-C-T			Likely benign (Jul 22, 2019)
19-918348-T-C			Likely benign (Nov 24, 2020)
19-918402-C-T			Benign (Feb 11, 2019)
19-918407-GGGGA-G			Benign (Jun 19, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KISS1R	protein_coding	protein_coding	ENST00000234371	5	3729

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.436	0.557	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.890	168	204	0.824	0.00000929	2363
Missense in Polyphen		68	84.299	0.80665		977
Synonymous	1.68	81	103	0.789	0.00000488	918
Loss of Function	2.29	2	9.72	0.206	4.16e-7	106

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for metastin (kisspeptin-54 or kp-54), a C- terminally amidated peptide of KiSS1. KiSS1 is a metastasis suppressor protein that suppresses metastases in malignant melanomas and in some breast carcinomas without affecting tumorigenicity. The metastasis suppressor properties may be mediated in part by cell cycle arrest and induction of apoptosis in malignant cells. The receptor is essential for normal gonadotropin-released hormone physiology and for puberty. The hypothalamic KiSS1/KISS1R system is a pivotal factor in central regulation of the gonadotropic axis at puberty and in adulthood. The receptor is also probably involved in the regulation and fine- tuning of trophoblast invasion generated by the trophoblast itself. Analysis of the transduction pathways activated by the receptor identifies coupling to phospholipase C and intracellular calcium release through pertussis toxin-insensitive G(q) proteins. {ECO:0000269|PubMed:15020672}.
• Disease: DISEASE: Hypogonadotropic hypogonadism 8 with or without anosmia (HH8) [MIM:614837]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic- pituitary axis. In some cases, it is associated with non- reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269|PubMed:12944565, ECO:0000269|PubMed:14573733, ECO:0000269|PubMed:15598687, ECO:0000269|PubMed:17164310, ECO:0000269|PubMed:23643382, ECO:0000269|PubMed:25077900}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in KISS1R as well as in other HH- associated genes including FGFR1 and IL17RD (PubMed:23643382). {ECO:0000269|PubMed:23643382}.; DISEASE: Precocious puberty, central 1 (CPPB1) [MIM:176400]: A condition defined as the development of secondary sexual characteristics in boys and girls at a chronological age that is 2.5 standard deviations below the mean age at onset of puberty in the population. Central precocious puberty results from premature activation of the hypothalamic-pituitary-gonadal axis. {ECO:0000269|PubMed:18272894}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neuroactive ligand-receptor interaction - Homo sapiens (human);Signaling by GPCR;Signal Transduction;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.160

Haploinsufficiency Scores

• pHI: 0.118
• hipred: N
• hipred_score: 0.367
• ghis: 0.436

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.779

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kiss1r
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); growth/size/body region phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;neuropeptide signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane;cell surface;integral component of membrane;intracellular membrane-bounded organelle
• Molecular function: protein binding;neuropeptide receptor activity;G protein-coupled peptide receptor activity