TAC4

protein-coding

tachykinin precursor 4, the group of Tachykinin precursors

Gene summary

This gene is a member of the tachykinin family of neurotransmitter-encoding genes. Tachykinin proteins are cleaved into small, secreted peptides that activate members of a family of receptor proteins. The products of this gene preferentially activate tachykinin receptor 1, and are thought to regulate peripheral endocrine and paracrine functions including blood pressure, the immune system, and endocrine gland secretion. The products of this gene lack a dibasic cleavage site found in other tachykinin proteins. Consequently, the nature of the cleavage products generated in vivo remains to be determined. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001077506.2

Inheritance

—

ClinVar variants

U:11B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.92

Max pathogenic AF

—

Genomic locus

chr17:49,838,300-49,848,069

External References & Databases

Ensembl (ENSG00000176358)

Transcript & Mutation Effects

hg38 • Region Span ~9.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TAC4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 10

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001077506.2. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			9 clinvar	1 clinvar		10
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	11	1	0	12

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001077506.2	RefSeq	NP_001070974.1	5	MANE Select
ENST00000436235.6	Ensembl	ENSP00000399702.1	5	MANE Select
NM_001077503.2	RefSeq	NP_001070971.1	4	Standard
NM_001077504.2	RefSeq	NP_001070972.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Peptide GPCRs

Biological Process

inflammatory response
positive regulation of cytosolic calcium ion concentration
tachykinin receptor signaling pathway
regulation of blood pressure
positive regulation of flagellated sperm motility

Molecular Function

substance P receptor binding

Cellular Component

extracellular space
cell

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000334568
Coding exons: 5
Length: 9709
Individuals with no LoFs: 120507
Homozygous LoFs: 169
Heterozygous LoFs: 4118
Defined: 124794
p: 0.0173

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0665	58	59.4	0.976	0.00000303	716
Missense (PolyPhen)		19	17.776	1.0689		222
Synonymous	-0.109	27	26.3	1.03	0.00000153	225
Loss of Function	0.210	7	7.63	0.918	4.09e-7	81

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0016	0.0016	notable
Latino/Admixed American	0.077	0.076	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.067	0.067	notable
Finnish	0.012	0.012	notable
European (Non-Finnish)	0.00074	0.00073	rare
South Asian	0.0051	0.0051	notable
Other	0.014	0.014	notable

dbNSFP Gene Annotations

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. Endokinin-A induces thermal hyperalgesia and pain-related behavior such as scratching following intrathecal administration in rats. These effects are suppressed by treatment with endokinin- C. Endokinin-A/B reduces arterial blood pressure and increases sperm motility. {ECO:0000269|PubMed:12716968, ECO:0000269|PubMed:17101218, ECO:0000269|PubMed:17437961, ECO:0000269|PubMed:17655832}.;

Recessive Scores

pRec: 0.202

Intolerance Scores

LoFtool: 0.557
RVIS EVS: 0.21
RVIS percentile EVS: 67.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0378

Gene Damage Prediction

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