MIEN1

Chr 17

migration and invasion enhancer 1

Also known as: C17orf37, C35, ORB3, RDX12, XTP4

The MIEN1 protein increases cell migration by inducing filopodia formation at the leading edge of migrating cells and negatively regulates apoptosis, possibly through control of CASP3. Mutations cause disease through a dominant-negative mechanism. The inheritance pattern and specific neurological phenotypes associated with MIEN1 mutations are not established in the provided data.

Summary from RefSeq, UniProt, Mechanism
Research Assistant →
0
Active trials
4
Pubs (1 yr)
8
P/LP submissions
0%
P/LP missense
0.72
LOEUF
DN
Mechanism· predicted
Clinical SummaryMIEN1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.55) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 17 VUS of 29 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.72LOEUF
pLI 0.553
Z-score 2.02
OE 0.15 (0.050.72)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
0.22Z-score
OE missense 0.92 (0.751.14)
59 obs / 64.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.15 (0.050.72)
00.351.4
Missense OE0.92 (0.751.14)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 1 / 6.6Missense obs/exp: 59 / 64.1Syn Z: 0.34
DN
0.6452th %ile
GOF
0.5857th %ile
LOF
0.3357th %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

29 submitted variants in ClinVar

Classification Summary

Pathogenic8
VUS17
Likely Benign1
8
Pathogenic
17
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
0
15
2
0
17
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total01610026

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

View in ClinVar →

Protein Context — Lollipop Plot

MIEN1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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