NET1

Chr 10

neuroepithelial cell transforming 1

Also known as: ARHGEF8, NET1A

This gene encodes a guanine nucleotide exchange factor that activates RhoA GTPase by catalyzing the exchange of GDP for GTP and may function in DNA damage repair after ionizing radiation. NET1 is tolerant to loss-of-function variants (pLI near 0, LOEUF 0.77), but pathogenic variants have not been established to cause human disease. Currently, there are no well-defined clinical phenotypes or inheritance patterns associated with NET1 mutations in pediatric patients.

Summary from RefSeq, UniProt
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1
Active trials
14
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.77
LOEUF
DN
Mechanism· predicted
Clinical SummaryNET1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.77LOEUF
pLI 0.000
Z-score 2.50
OE 0.49 (0.330.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.08Z-score
OE missense 0.83 (0.750.92)
275 obs / 330.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.49 (0.330.77)
00.351.4
Missense OE0.83 (0.750.92)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 14 / 28.3Missense obs/exp: 275 / 330.5Syn Z: 0.30
DN
0.6259th %ile
GOF
0.6249th %ile
LOF
0.4038th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NET1 · protein map & ClinVar variants

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

Clinical Literature
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