KISS1

KiSS-1 metastasis suppressor, the group of Neuropeptides

Basic information

Region (hg38): 1:204190340-204196491

Links

ENSG00000170498 ∙ NCBI:3814 ∙ OMIM:603286 ∙ HGNC:6341 ∙ Uniprot:Q15726 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypogonadotropic hypogonadism (Supportive), mode of inheritance: AD
• hypogonadotropic hypogonadism 13 with or without anosmia (Limited), mode of inheritance: AR
• hypogonadotropic hypogonadism 13 with or without anosmia (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypogonadotropic hypogonadism 13 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	20301509; 22335740

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KISS1 gene.

• not provided (29 variants)
• Inborn genetic diseases (7 variants)
• not specified (3 variants)
• Hypogonadotropic hypogonadism 13 with or without anosmia (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KISS1 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				5	1	6
missense			10	2	4	16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1	11	12
Total	0	0	10	8	16

Variants in KISS1

This is a list of pathogenic ClinVar variants found in the KISS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-204190409-T-TTG			Benign (Jun 19, 2018)
1-204190411-C-G			Benign (Oct 31, 2018)
1-204190413-CG-C			Benign (Jun 19, 2018)
1-204190414-G-C			Benign (Jul 09, 2018)
1-204190416-C-CA			Benign (Aug 07, 2018)
1-204190474-A-ACCTGCGCCCTCAGCCCCGCC			Benign (May 25, 2021)
1-204190483-CT-C		not specified • Hypogonadotropic hypogonadism 13 with or without anosmia	Benign (Jan 29, 2024)
1-204190526-C-T			Likely benign (Apr 09, 2018)
1-204190534-T-C		not specified	Uncertain significance (Nov 21, 2023)
1-204190552-A-G			Uncertain significance (Oct 03, 2023)
1-204190561-A-T		not specified	Uncertain significance (Oct 03, 2023)
1-204190562-G-C		Hypogonadotropic hypogonadism 13 with or without anosmia	Pathogenic (Feb 16, 2012)
1-204190571-C-T			Likely benign (Aug 23, 2022)
1-204190573-G-T			Benign (Jan 18, 2024)
1-204190608-T-A		not specified	Uncertain significance (May 23, 2023)
1-204190616-G-A			Benign (Dec 21, 2021)
1-204190618-G-A		Disorder of sexual differentiation	Uncertain significance (Sep 01, 2021)
1-204190633-G-A			Uncertain significance (Apr 17, 2023)
1-204190633-G-C		not specified • Hypogonadotropic hypogonadism 13 with or without anosmia	Benign/Likely benign (Oct 22, 2023)
1-204190634-G-T			Likely benign (Mar 30, 2018)
1-204190638-G-C		not specified	Uncertain significance (Mar 01, 2023)
1-204190647-C-T			Uncertain significance (Dec 14, 2021)
1-204190659-G-C		not specified • Hypogonadotropic hypogonadism 13 with or without anosmia	Benign (Jan 31, 2024)
1-204190661-G-A		KISS1-related disorder	Likely benign (Mar 06, 2019)
1-204190671-C-T			Uncertain significance (Apr 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KISS1	protein_coding	protein_coding	ENST00000367194	2	6146

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.490	0.438	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0964	77	74.7	1.03	0.00000334	829
Missense in Polyphen		20	17.939	1.1149		171
Synonymous	-0.725	43	37.4	1.15	0.00000175	305
Loss of Function	1.26	0	1.85	0.00	7.91e-8	19

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: Metastasis suppressor protein in malignant melanomas and in some breast cancers. May regulate events downstream of cell- matrix adhesion, perhaps involving cytoskeletal reorganization. Generates a C-terminally amidated peptide, metastin which functions as the endogenous ligand of the G-protein coupled receptor GPR54. Activation of the receptor inhibits cell proliferation and cell migration, key characteristics of tumor metastasis. Kp-10 is a decapeptide derived from the primary translation product, isolated in conditioned medium of first trimester trophoblast. Kp-10, but not other kisspeptins, increased intracellular Ca(2+) levels in isolated first trimester trophoblasts. Kp-10 is a paracrine/endocrine regulator in fine- tuning trophoblast invasion generated by the trophoblast itself. The receptor is also essential for normal gonadotropin-released hormone physiology and for puberty. The hypothalamic KiSS1/GPR54 system is a pivotal factor in central regulation of the gonadotropic axis at puberty and in adulthood. {ECO:0000269|PubMed:11060311, ECO:0000269|PubMed:11385580, ECO:0000269|PubMed:15500545, ECO:0000269|PubMed:9185708}.
• Disease: DISEASE: Hypogonadotropic hypogonadism 13 with or without anosmia (HH13) [MIM:614842]: 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:22335740}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: 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: 0.156

Haploinsufficiency Scores

• pHI: 0.0423
• hipred: N
• hipred_score: 0.146

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.743

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kiss1
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; reproductive system 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; 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; renal/urinary system phenotype; liver/biliary system phenotype

Zebrafish Information Network

• Gene name: kiss1
• Affected structure: raphe nucleus
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: cytoskeleton organization;G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;negative regulation of cell population proliferation;positive regulation of luteinizing hormone secretion;positive regulation of MAPK cascade;positive regulation of synaptic transmission;positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway;generation of ovulation cycle rhythm;positive regulation of growth hormone secretion
• Cellular component: extracellular region;extracellular space;cytoplasm;apical plasma membrane;neuron projection;neuronal cell body
• Molecular function: protein binding;kisspeptin receptor binding