MICALL1

Chr 22

MICAL like 1

Also known as: MICAL-L1, MIRAB13

NCBI Gene: 85377ENSG00000100139UniProt: Q8N3F8OMIM: 619563

MICALL1 encodes a lipid-binding protein that regulates endosome membrane tubulation and slow endocytic recycling, and plays a role in ciliogenesis by recruiting proteins to the primary cilium. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy. The gene shows low constraint to loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.75
Clinical Summary— MICALL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 159 VUS of 210 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
0.75LOEUF
pLI 0.000
Z-score 2.69
OE 0.50 (0.34–0.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.98Z-score
OE missense 0.88 (0.81–0.95)
444 obs / 505.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.50 (0.34–0.75)
0≤0.351.4
Missense OE0.88 (0.81–0.95)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 17 / 33.9Missense obs/exp: 444 / 505.8Syn Z: 0.94
DN
0.6649th %ile
GOF
0.6442th %ile
LOF
0.3744th %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

210 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic3
VUS159
Likely Benign8
Conflicting1
22
Pathogenic
3
Likely Pathogenic
159
VUS
8
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
3
0
3
VUS
0
157
2
0
159
Likely Benign
0
6
0
2
8
Benign
0
0
0
0
0
Conflicting
—1
Total0163272193

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

View in ClinVar →

Protein Context — Lollipop Plot

MICALL1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients