TMPRSS11F

Chr 4

transmembrane serine protease 11F

Also known as: HATL4

NCBI Gene: 389208 ENSG00000198092 UniProt: Q6ZWK6

This gene encodes a serine protease predicted to function in proteolysis and establishment of skin barrier at the cell surface. The gene shows no constraint against loss-of-function variants (pLI near 0, LOEUF ~1), and no established disease associations have been reported in humans. Clinical significance of variants in this gene remains unclear.

ResearchSummary from RefSeq, UniProt

Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within establishment of skin barrier. Located in cell surface. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.00

Clinical Summary— TMPRSS11F

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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

52 VUS of 69 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?

1.00LOEUF

pLI 0.000

Z-score 1.56

OE 0.67 (0.47–1.00)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.39Z-score

OE missense 0.93 (0.83–1.04)

212 obs / 228.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.47–1.00)

0≤0.351.4

Missense OE?0.93 (0.83–1.04)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 18 / 26.7Missense obs/exp: 212 / 228.5Syn Z: -0.45

This gene — mechanism propensity

0.7228th %ile

GOF

0.6345th %ile

LOF

0.3065th %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

69 submitted variants in ClinVar

ClinVar

Classification Summary

VUS52

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	52	52
Likely Benign	5	5
Benign	0	0
Total	57	57

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap TMPRSS11F — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →