GeneBe

TAC3

tachykinin precursor 3, the group of Tachykinin precursors

Basic information

Region (hg38): 12:57010000-57028883

Previous symbols: [ "NKNB" ]

Links

ENSG00000166863 ∙ NCBI:6866 ∙ OMIM:162330 ∙ HGNC:11521 ∙ Uniprot:Q9UHF0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • hypogonadotropic hypogonadism (Supportive), mode of inheritance: AD
  • hypogonadotropic hypogonadism 10 with or without anosmia (Strong), mode of inheritance: AR
  • hypogonadotropic hypogonadism 10 with or without anosmia (Strong), mode of inheritance: AR
  • hypogonadotropic hypogonadism 10 with or without anosmia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Hypogonadotropic hypogonadismAREndocrineIn 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 diseaseEndocrine19079066

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TAC3 gene.

  • not_specified (17 variants)
  • not_provided (12 variants)
  • Hypogonadotropic_hypogonadism_10_with_or_without_anosmia (3 variants)
  • Delayed_puberty (2 variants)
  • TAC3-related_disorder (2 variants)
  • Hypogonadotropic_hypogonadism_7_with_or_without_anosmia (1 variants)
  • Hypogonadotropic_hypogonadism (1 variants)
  • Infertility_disorder (1 variants)
  • Hypogonadotropic_hypogonadism_10_without_anosmia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TAC3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000013251.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
 3
missense
1
clinvar
2
clinvar
19
clinvar
1
clinvar
 23
nonsense
0
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total 2 4 19 3 1

Highest pathogenic variant AF is 0.000325866

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
TAC3protein_codingprotein_codingENST00000458521 518884
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.01170.8571257190291257480.000115
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.6905065.70.7610.00000373791
Missense in Polyphen1517.0460.87998217
Synonymous-0.1782826.81.040.00000172228
Loss of Function1.2347.700.5204.32e-785

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001530.00153
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.000008790.00000879
Middle Eastern0.00005440.0000544
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles (By similarity). Is a critical central regulator of gonadal function. {ECO:0000250, ECO:0000269|PubMed:19079066}.;
Disease
DISEASE: Hypogonadotropic hypogonadism 10 with or without anosmia (HH10) [MIM:614839]: 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}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Signaling by GPCR;Signal Transduction;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Tachykinin receptors bind tachykinins;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;GPCR signaling-G alpha i;G alpha (q) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

pRec
0.181

Intolerance Scores

loftool
0.380
rvis_EVS
0.04
rvis_percentile_EVS
56.64

Haploinsufficiency Scores

pHI
0.0597
hipred
N
hipred_score
0.153
ghis
0.469

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.150

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Tac2
Phenotype
growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; reproductive system phenotype; normal phenotype; digestive/alimentary phenotype;

Gene ontology

Biological process
G protein-coupled receptor signaling pathway;tachykinin receptor signaling pathway;neuropeptide signaling pathway;female pregnancy
Cellular component
extracellular region;extracellular space
Molecular function
signaling receptor binding