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 7 with or without anosmia (Strong), mode of inheritance: AR
• hypogonadotropic hypogonadism (Supportive), mode of inheritance: AD
• hypogonadotropic hypogonadism 10 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	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	Endocrine	19079066

ClinVar

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

• not provided (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.

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				2		2
missense		1	8		1	10
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region				1		1
non coding				2	4	6
Total	1	2	8	4	5

Highest pathogenic variant AF is 0.000348

Variants in TAC3

This is a list of pathogenic ClinVar variants found in the TAC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-57010271-G-A			Benign (Mar 03, 2015)
12-57010288-A-G		not specified	Likely benign (Mar 08, 2016)
12-57012393-G-A		not specified	Uncertain significance (Aug 15, 2024)
12-57012420-G-A		not specified	Uncertain significance (Jul 02, 2024)
12-57012423-C-T			Uncertain significance (Jul 11, 2022)
12-57012424-G-A			Likely benign (Jun 06, 2018)
12-57012450-A-G		not specified	Benign (Jan 22, 2024)
12-57012660-T-C			Benign (Jun 19, 2018)
12-57012845-A-G		Hypogonadotropic hypogonadism 10 without anosmia	Pathogenic (Mar 01, 2009)
12-57012866-T-C		Delayed puberty • Infertility disorder	Conflicting classifications of pathogenicity (Oct 01, 2023)
12-57013358-C-G			Likely pathogenic (Sep 09, 2022)
12-57013359-G-A		Hypogonadotropic hypogonadism 10 with or without anosmia	Uncertain significance (Jan 17, 2024)
12-57013359-G-T		Hypogonadotropic hypogonadism 7 with or without anosmia • Delayed puberty	Likely pathogenic (Nov 01, 2014)
12-57013365-C-T		TAC3-related disorder	Uncertain significance (Jan 14, 2023)
12-57013366-G-A			Likely benign (Oct 01, 2022)
12-57013379-T-A		not specified	Uncertain significance (Dec 13, 2023)
12-57013379-T-C		not specified	Uncertain significance (May 18, 2023)
12-57013389-C-G			Pathogenic (Jul 21, 2022)
12-57013569-G-A			Likely benign (Apr 24, 2018)
12-57013626-G-A		not specified	Uncertain significance (Oct 26, 2022)
12-57013646-A-G		not specified	Uncertain significance (Oct 09, 2024)
12-57013652-T-C		Hypogonadotropic hypogonadism 10 with or without anosmia	Uncertain significance (Apr 08, 2024)
12-57015455-G-A			Benign (Jun 19, 2018)
12-57015484-A-G			Likely benign (Apr 16, 2019)
12-57015597-C-A			Benign (Jun 19, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TAC3	protein_coding	protein_coding	ENST00000458521	5	18884

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0117	0.857	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.690	50	65.7	0.761	0.00000373	791
Missense in Polyphen		15	17.046	0.87998		217
Synonymous	-0.178	28	26.8	1.04	0.00000172	228
Loss of Function	1.23	4	7.70	0.520	4.32e-7	85

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00153	0.00153
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

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

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

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