HTN1

Chr 4

histatin 1

Also known as: HIS1, Hst1

NCBI Gene: 3346 ENSG00000126550 UniProt: P15515 OMIM: 142701

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.

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, Aug 2014]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.74

Clinical Summary— HTN1

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Population Constraint (gnomAD)

Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

5 VUS of 7 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.74LOEUF

pLI 0.042

Z-score 0.52

OE 0.68 (0.27–1.74)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.85Z-score

OE missense 1.45 (1.13–1.84)

41 obs / 28.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.68 (0.27–1.74)

0≤0.351.4

Missense OE?1.45 (1.13–1.84)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 2 / 3.0Missense obs/exp: 41 / 28.3Syn Z: -0.52

This gene — mechanism propensity

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

7 submitted variants in ClinVar

ClinVar

Classification Summary

VUS5

Benign1

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

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

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap HTN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →