HTN3

Chr 4

histatin 3

Also known as: HIS2, HTN2, HTN5, Hst 3, PB

NCBI Gene: 3347 ENSG00000205649 UniProt: P15516 OMIM: 142702

HTN3 encodes histatin-3, a small histidine-rich cationic protein found in saliva that functions as an antimicrobial peptide with antibacterial and antifungal activities, and contributes to wound healing and formation of the protective enamel pellicle on tooth surfaces. Based on the available data, no human diseases have been definitively associated with HTN3 mutations. An inheritance pattern cannot be determined from the current information.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.89

Clinical Summary— HTN3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 3 VUS of 6 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.89LOEUF

pLI 0.000

Z-score -0.47

OE 1.23 (0.65–1.89)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.47Z-score

OE missense 1.27 (0.95–1.70)

31 obs / 24.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.23 (0.65–1.89)

0≤0.351.4

Missense OE?1.27 (0.95–1.70)

0≤0.61.4

Synonymous OE?1.37

0≤1.21.6

LoF obs/exp: 6 / 4.9Missense obs/exp: 31 / 24.5Syn Z: -0.78

This gene — mechanism propensity

0.88top 5%

GOF

0.5465th %ile

LOF

0.1796th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

6 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS3

Likely Benign1

Benign1

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	1	0	1
Likely Pathogenic	0	0	0
VUS	0	3	3
Likely Benign	0	1	1
Benign	0	1	1
Total	1	5	6

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

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22 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap HTN3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →