MICAL1

Chr 6

microtubule associated monooxygenase, calponin and LIM domain containing 1

Also known as: MICAL, MICAL-1, NICAL

NCBI Gene: 64780ENSG00000135596UniProt: Q8TDZ2

This gene encodes an enzyme that oxidizes methionine residues on actin, thereby promoting depolymerization of actin filaments. This protein interacts with and regulates signalling by NEDD9/CAS-L (neural precursor cell expressed, developmentally down-regulated 9). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

274
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MICAL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
163 VUS of 274 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.92LOEUF
pLI 0.000
Z-score 2.09
OE 0.71 (0.56–0.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.24Z-score
OE missense 1.03 (0.96–1.09)
655 obs / 638.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.71 (0.56–0.92)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.96–1.09)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 43 / 60.5Missense obs/exp: 655 / 638.2Syn Z: 0.32

ClinVar Variant Classifications

274 submitted variants in ClinVar

ClinVar

Classification Summary

VUS163
Likely Benign110
Benign1
163
VUS
110
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
9
131
20
3
163
Likely Benign
10
0
56
44
110
Benign
0
0
0
1
1
Total191317648274

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

View in ClinVar →

Protein Context — Lollipop Plot

MICAL1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — MICAL1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
High MICAL1 expression correlates with cancer progression and immune infiltration in renal clear cell carcinoma.
Yang Y et al.·BMC Cancer
2022
MICAL1 facilitates breast cancer cell proliferation via ROS-sensitive ERK/cyclin D pathway.
Deng W et al.·J Cell Mol Med
2018
MICAL1 controls cell invasive phenotype via regulating oxidative stress in breast cancer cells.
Deng W et al.·BMC Cancer
2016
Semaphorin3a promotes advanced diabetic nephropathy.
Aggarwal PK et al.·Diabetes
2015
A novel splicing variant in MICAL-1 gene is associated with epilepsy.
Yang H et al.·Eur J Med Genet
2024Case report
Unveiling novel potential drug targets for lung cancer through Mendelian randomization analysis.
Huang Y et al.·Sci Rep
2025
Development and clinical validation of a novel 9-gene prognostic model based on multi-omics in pancreatic adenocarcinoma.
Xu D et al.·Pharmacol Res
2021Functional
Mutations in MICAL-1cause autosomal-dominant lateral temporal epilepsy.
Dazzo E et al.·Ann Neurol
2018
A neurodevelopmental disorder associated with a loss-of-function missense mutation in RAB35.
Aguila A et al.·J Biol Chem
2024Case report
A de novo pathogenic variant in MICAL-1 causes epilepsy with auditory features.
Bonanni P et al.·Epilepsia Open
2024Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools