HTN3

Chr 4

histatin 3

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

Histatins are cationic and histidine-rich peptides mainly found in the saliva of higher primates (PubMed:3286634). They are considered to be major precursors of the protective proteinaceous structure on tooth surfaces (enamel pellicle). Hsts can be divided into two major groups according to their biological functions: antimicrobial Hsts (e.g. Hst 5/HTN3) and cell-activating Hsts (e.g. Hst 1/HTN1, Hst 2/HTN1 and Hst 3/HTN3) (PubMed:32225006)

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.89

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in HTN3?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,000

73 rare PASS variants

Rare truncating (LoF)

1 in 2,900

23 rare PASS variants

Rare synonymous (reference)

1 in 2,100

18 rare PASS variants

Rare missense and truncating variants are carried at similar rates in HTN3; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~555k	1 in 620	1 in 2,300
South Asian	~43k	1 in 540	1 in 1,100
Remaining (unassigned)	~30k	1 in 950	1 in 2,300
European (Finnish)	~27k	≈ 1 in 8,900	none seen
Admixed American	~22k	1 in 570	1 in 2,800
African / African American	~21k	1 in 1,100	1 in 2,200
East Asian	~20k	1 in 1,400	1 in 1,300
Ashkenazi Jewish	~13k	≈ 1 in 3,300	≈ 1 in 6,500
Middle Eastern	~2,880	≈ 1 in 740	≈ 1 in 2,100

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 1 of 4 coding exons well covered in gnomAD exomes; exons 3, 4, 5 marginal. Genomes: all 4.? see exons ↓