GeneBe

KISS1R

protein-coding

KISS1 receptor, the group of Peptide receptors

Gene summary

The protein encoded by this gene is a galanin-like G protein-coupled receptor that binds metastin, a peptide encoded by the metastasis suppressor gene KISS1. The tissue distribution of the expressed gene suggests that it is involved in the regulation of endocrine function, and this is supported by the finding that this gene appears to play a role in the onset of puberty. Mutations in this gene have been associated with hypogonadotropic hypogonadism and central precocious puberty. [provided by RefSeq, Jul 2008]

Previous symbols:
  • GPR54

MANE transcript

NM_032551.5

Inheritance

AR, AD

ClinVar variants

P:20U:114B:36

Top phenotype

Hypogonadotropic hypogonadism 8 with or without anosmia

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr19:917,287-921,005

External References & Databases

Ensembl (ENSG00000116014)NCBI Gene (84634)OMIM (604161)HGNC:4510GenCCUniProt (Q969F8)AlphaFoldClinVar (KISS1R)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~3.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypogonadotropic hypogonadism 8 with or without anosmiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013910

Submitter: PanelApp Australia

hypogonadotropic hypogonadism 8 with or without anosmiaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013910

Submitter: Ambry Genetics

hypogonadotropic hypogonadismSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018555

Submitter: Orphanet

central precocious puberty 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0008302

Submitter: Ambry Genetics

hypogonadotropic hypogonadism 8 with or without anosmiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013910

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Hypogonadotropic hypogonadism 8 with or without anosmiaAR

Manifestation: Endocrine; Neurologic

Intervention: Endocrine

Rationale: 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

Comments: In Precocious puberty, treatment with gonadotropin-releasing hormone receptor analogs/LHRH agonists can be beneficial

Refs: 11600530; 12788910; 12788881; 14573733; 18272894; 20301509Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KISS1R variants in ClinVar

13 Conditions Cataloged
not providedTotal: 111
Inborn genetic diseasesTotal: 78
KISS1R-related disorderTotal: 18
not specifiedTotal: 16
Hypogonadotropic hypogonadism 8 with or without anosmiaTotal: 15
Central precocious puberty 1Total: 7
Hypogonadotropic hypogonadism 8 without anosmiaTotal: 6
Hypogonadotropic hypogonadismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032551.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
28
clinvar
2
clinvar
 30
missense
1
clinvar
3
clinvar
108
clinvar
5
clinvar
1
clinvar
 118
nonsense
2
clinvar
4
clinvar
1
clinvar
 7
start loss
1
clinvar
 1
frameshift
3
clinvar
2
clinvar
3
clinvar
 8
splice donor/acceptor (+/-2bp)
2
clinvar
3
clinvar
1
clinvar
 6
Total812114333170

Highest pathogenic variant AF is 0.00006696567

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_032551.5RefSeqNP_115940.25MANE Select
ENST00000234371.10EnsemblENSP00000234371.35MANE Select
ENST00000592648.1EnsemblENSP00000467666.12Standard
ENST00000606939.2EnsemblENSP00000475639.14Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Neuroactive ligand-receptor interaction - Homo sapiens (human)
  • Signaling by GPCR
  • Signal Transduction
  • Peptide ligand-binding receptors
  • Class A/1 (Rhodopsin-like receptors)

Biological Process

  • G protein-coupled receptor signaling pathway
  • neuropeptide signaling pathway

Molecular Function

  • protein binding
  • neuropeptide receptor activity
  • G protein-coupled peptide receptor activity

Cellular Component

  • plasma membrane
  • integral component of plasma membrane
  • cell surface
  • integral component of membrane
  • intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000234371
Coding exons
5
Length
3729
Individuals with no LoFs
0
Homozygous LoFs
0
Heterozygous LoFs
0
Defined
0
p
0.00
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.8901682040.8240.000009292363
Missense (PolyPhen)6884.2990.80665977
Synonymous1.68811030.7890.00000488918
Loss of Function2.2929.720.2064.16e-7106

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.160

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.779

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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