HTN1

Chr 4

histatin 1

Also known as: HIS1, Hst1

The HTN1 gene encodes histatin 1, a small histidine-rich cationic protein secreted in saliva that functions as an antimicrobial peptide and promotes wound healing in oral and non-oral mucosa. HTN1 is tolerant to loss-of-function variants (LOEUF 1.74), and no pediatric neurological diseases have been definitively associated with HTN1 mutations. This gene primarily relates to oral health and innate immunity rather than neurological function.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.74
Clinical SummaryHTN1
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.74LOEUF
pLI 0.042
Z-score 0.52
OE 0.68 (0.271.74)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.85Z-score
OE missense 1.45 (1.131.84)
41 obs / 28.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.68 (0.271.74)
00.351.4
Missense OE1.45 (1.131.84)
00.61.4
Synonymous OE1.22
01.21.6
LoF obs/exp: 2 / 3.0Missense obs/exp: 41 / 28.3Syn Z: -0.52
DN
0.93top 5%
GOF
0.6834th %ile
LOF
0.08100th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HTN1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC