HTN3

protein-coding

histatin 3, the group of Histatins and statherin

Gene summary

This gene encodes a member of the histatin family of small, histidine-rich, cationic proteins. They function as antimicrobial peptides and are important components of the innate immune system. Histatins are found in saliva and exhibit antibacterial, antifungal activities and function in wound healing. [provided by RefSeq, Sep 2014]

MANE transcript

NM_000200.3

Inheritance

—

ClinVar variants

U:5B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.23

Max pathogenic AF

—

Genomic locus

chr4:70,028,455-70,036,538

External References & Databases

Ensembl (ENSG00000205649)

Transcript & Mutation Effects

hg38 • Region Span ~8.1 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 HTN3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 4

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000200.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			4 clinvar	1 clinvar	1 clinvar	6
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	5	1	1	7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000200.3	RefSeq	NP_000191.1	4	MANE Select
ENST00000673563.1	Ensembl	ENSP00000500623.1	4	MANE Select
ENST00000381057.3	Ensembl	ENSP00000370445.3	3	Standard
ENST00000381057.4	Ensembl	ENSP00000370445.3	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Salivary secretion - Homo sapiens (human)
Antimicrobial peptides
Innate Immune System
Immune System

Biological Process

antimicrobial humoral response
biomineral tissue development
killing of cells of other organism
defense response to bacterium
defense response to fungus

Molecular Function

protein binding
metal ion binding

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000530128
Coding exons: 4
Length: 8126
Individuals with no LoFs: 123271
Homozygous LoFs: 167
Heterozygous LoFs: 2264
Defined: 125702
p: 0.00972

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.469	31	24.5	1.27	0.00000104	327
Missense (PolyPhen)		3	4.0898	0.73353		60
Synonymous	-0.781	10	7.31	1.37	3.13e-7	76
Loss of Function	-0.473	6	4.87	1.23	2.69e-7	63

Population LoF Frequency

Population	CAF	p-value	Status
African	0.15	0.14	notable
Latino/Admixed American	0.0056	0.0052	notable
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00071	0.00071	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00026	0.00026	rare
South Asian	0.00030	0.00029	rare
Other	0.0032	0.0031	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Histatins are salivary proteins that are considered to be major precursors of the protective proteinaceous structure on tooth surfaces (enamel pellicle). In addition, histatins exhibit antibacterial and antifungal activities. His3-(20-43)-peptide (histatin-5) is especially effective against C.albicans and C.neoformans, and inhibits Lys-gingipain and Arg-gingipain (rgpB) from P.gingivalis. In addition, His3-(20-43)-peptide is a potent inhibitor of metalloproteinases MMP2 and MMP9. {ECO:0000269|PubMed:11179305, ECO:0000269|PubMed:8945538}.;

Intolerance Scores

LoFtool: 0.741
RVIS EVS: 0.95
RVIS percentile EVS: 89.91

Essentials

Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.102

Gene Damage Prediction

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