MLC1

Chr 22AR

modulator of VRAC current 1

Also known as: LVM, MLC, VL

NCBI Gene: 23209ENSG00000100427UniProt: Q15049OMIM: 605908

This gene encodes a transmembrane protein expressed in brain astrocytes that regulates astrocyte response to hypo-osmotic conditions and may function in transport across blood-brain and cerebrospinal fluid barriers. Mutations cause megalencephalic leukoencephalopathy with subcortical cysts, a progressive white matter disorder typically presenting in infancy with macrocephaly. The condition follows autosomal recessive inheritance.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.162 OMIM phenotypes
Clinical Summary— MLC1
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Gene-Disease Validity (ClinGen)
megalencephalic leukoencephalopathy with subcortical cysts 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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
100 unique Pathogenic / Likely Pathogenic· 89 VUS of 400 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — MLC1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.16LOEUF
pLI 0.000
Z-score 1.03
OE 0.74 (0.49–1.16)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.20Z-score
OE missense 0.96 (0.86–1.08)
210 obs / 218.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.74 (0.49–1.16)
0≤0.351.4
Missense OE0.96 (0.86–1.08)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 14 / 18.8Missense obs/exp: 210 / 218.4Syn Z: 0.41
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMLC1-related leukoencephalopathy megalencephalic with subcortical cystsLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6454th %ile
GOF
0.6930th %ile
LOF
0.3065th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic54
VUS89
Likely Benign195
Benign9
Conflicting1
46
Pathogenic
54
Likely Pathogenic
89
VUS
195
Likely Benign
9
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
2
32
0
46
Likely Pathogenic
36
15
3
0
54
VUS
1
66
17
5
89
Likely Benign
0
3
101
91
195
Benign
0
0
9
0
9
Conflicting
—1
Total498616296394

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

View in ClinVar →

Protein Context — Lollipop Plot

MLC1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
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 5 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