LLGL1

Chr 17

LLGL scribble cell polarity complex component 1

Also known as: DLG4, HUGL, HUGL-1, HUGL1, LLGL, Lgl1, Mgl1

NCBI Gene: 3996 ENSG00000131899 UniProt: Q15334 OMIM: 600966

The protein maintains cell polarity and epithelial integrity as part of the cortical cytoskeleton, regulates mitotic spindle orientation in neuroepithelial cells, and is involved in axonogenesis through regulation of vesicular trafficking. Mutations cause autosomal recessive congenital hydrocephalus with severe developmental delays and brain malformations. This gene is highly intolerant to loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein that is similar to a tumor suppressor in Drosophila. The protein is part of a cytoskeletal network and is associated with nonmuscle myosin II heavy chain and a kinase that specifically phosphorylates this protein at serine residues. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.53

Clinical Summary— LLGL1

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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

152 VUS of 189 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.53LOEUF

pLI 0.000

Z-score 4.16

OE 0.35 (0.24–0.53)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.45Z-score

OE missense 0.84 (0.79–0.90)

575 obs / 681.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.24–0.53)

0≤0.351.4

Missense OE?0.84 (0.79–0.90)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 17 / 48.1Missense obs/exp: 575 / 681.9Syn Z: -2.16

ClinVar Variant Classifications

189 submitted variants in ClinVar

ClinVar

Classification Summary

VUS152

Likely Benign11

Benign11

152

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	152	0	0	152
Likely Benign	9	0	2	11
Benign	3	2	6	11
Total	164	2	8	174

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

View in ClinVar →

116 pathogenic / likely-pathogenic (of 122) ClinVar copy-number / structural variants overlap LLGL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →