LGI4

Chr 19AR

leucine rich repeat LGI family member 4

Also known as: AMC1, AMCNMY, LGIL3

NCBI Gene: 163175 ENSG00000153902 UniProt: Q8N135 OMIM: 608303

Involved in regulation of myelination. Predicted to be located in extracellular region. Predicted to be active in extracellular space. Implicated in arthrogryposis multiplex congenita-1 and childhood absence epilepsy. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.681 OMIM phenotype

Clinical Summary— LGI4

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

19 unique Pathogenic / Likely Pathogenic· 84 VUS of 158 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?

0.68LOEUF

pLI 0.007

Z-score 2.58

OE 0.36 (0.21–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.07Z-score

OE missense 0.84 (0.76–0.92)

283 obs / 338.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.21–0.68)

0≤0.351.4

Missense OE?0.84 (0.76–0.92)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 7 / 19.2Missense obs/exp: 283 / 338.5Syn Z: 0.89

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongLGI4-related arthrogryposis multiplex congenitaLOFAR

This gene — mechanism propensity

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

0.7327th %ile

GOF

0.7029th %ile

LOF

0.2873th %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

158 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9

Likely Pathogenic10

VUS84

Likely Benign21

Benign28

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	4	2	0	9
Likely Pathogenic	6	4	0	0	10
VUS	1	83	0	0	84
Likely Benign	0	6	3	12	21
Benign	0	2	17	9	28
Conflicting	—				2
Total	10	99	22	21	154

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap LGI4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →