GeneBe

TACR3

protein-coding

tachykinin receptor 3, the group of Tachykinin receptors

Gene summary

This gene belongs to a family of genes that function as receptors for tachykinins. Receptor affinities are specified by variations in the 5'-end of the sequence. The receptors belonging to this family are characterized by interactions with G proteins and 7 hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin neurokinin 3, also referred to as neurokinin B. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001059.3

Inheritance

AD, AR

ClinVar variants

P:22U:84B:36

Top phenotype

Hypogonadotropic hypogonadism

gnomAD constraint

pLI —, LoF o/e 1.24

Max pathogenic AF

—

Genomic locus

chr4:103,586,031-103,719,985

External References & Databases

Ensembl (ENSG00000169836)NCBI Gene (6870)OMIM (162332)HGNC:11528GenCCUniProt (P29371)AlphaFoldClinVar (TACR3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~134.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypogonadotropic hypogonadismSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018555

Submitter: Orphanet

hypogonadotropic hypogonadism 11 with or without anosmiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013913

Submitter: Labcorp Genetics (formerly Invitae)

Kallmann syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018800

Submitter: Orphanet

hypogonadotropic hypogonadism 11 with or without anosmiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013913

Submitter: PanelApp Australia

hypogonadotropic hypogonadism 11 with or without anosmiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013913

Submitter: G2P

Clinical Genomic Database (CGD)

Hypogonadotropic hypogonadismAR

Manifestation: Endocrine

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

Refs: 19079066; 20301509Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TACR3 variants in ClinVar

12 Conditions Cataloged
not providedTotal: 82
Inborn genetic diseasesTotal: 53
Hypogonadotropic hypogonadism 11 with or without anosmiaTotal: 38
not specifiedTotal: 16
TACR3-related disorderTotal: 13
Hypogonadotropic hypogonadismTotal: 3
Hypogonadotropic hypogonadism 7 with or without anosmiaTotal: 1
Delayed pubertyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001059.3. 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
5
clinvar
26
clinvar
2
clinvar
 33
missense
3
clinvar
3
clinvar
78
clinvar
8
clinvar
 92
nonsense
2
clinvar
7
clinvar
 9
start loss
0
frameshift
2
clinvar
2
clinvar
 4
splice donor/acceptor (+/-2bp)
1
clinvar
2
clinvar
1
clinvar
 4
Total81484342142

Highest pathogenic variant AF is 0.00046314034

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001059.3RefSeqNP_001050.15MANE Select
ENST00000304883.3EnsemblENSP00000303325.25MANE Select
ENST00001134610.1EnsemblENSP00000805630.15Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Calcium signaling pathway - Homo sapiens (human)
  • Neuroactive ligand-receptor interaction - Homo sapiens (human)
  • Peptide GPCRs
  • Signaling by GPCR
  • Signal Transduction

Biological Process

  • G protein-coupled receptor signaling pathway
  • tachykinin receptor signaling pathway
  • aging
  • positive regulation of heart rate
  • response to estradiol

Molecular Function

  • tachykinin receptor activity
  • protein binding

Cellular Component

  • nucleus
  • cytoplasm
  • plasma membrane
  • integral component of plasma membrane
  • dendrite membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000304883
Coding exons
5
Length
133786
Individuals with no LoFs
125634
Homozygous LoFs
0
Heterozygous LoFs
114
Defined
125748
p
0.000453
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.5772332590.8990.00001313036
Missense (PolyPhen)7693.8570.809741207
Synonymous0.04279898.50.9950.00000508949
Loss of Function-0.9722318.51.249.57e-7194

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000310.00031rare
Latino/Admixed American0.000200.00020rare
Ashkenazi Jewish0.000300.00030rare
East Asian0.000490.00049rare
Finnish00.0absent
European (Non-Finnish)0.000720.00072rare
South Asian0.000260.00026rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: This is a receptor for the tachykinin neuropeptide neuromedin-K (neurokinin B). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: neuromedin-K > substance K > substance P.;
Disease
DISEASE: Hypogonadotropic hypogonadism 11 with or without anosmia (HH11) [MIM:614840]: 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:19079066, 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 TACR3 as well as in other HH-associated genes including FGFR1, SPRY4 and KAL1 (PubMed:23643382). {ECO:0000269|PubMed:23643382}.;

Recessive Scores

pRec
0.143

Intolerance Scores

LoFtool
0.791
RVIS EVS
-0.34
RVIS percentile EVS
30.56

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.849

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.