LIMD1 encodes an adapter protein that functions as a transcriptional corepressor, regulates microRNA-mediated gene silencing, and is essential for P-body formation while also modulating multiple signaling pathways including Hippo and Wnt signaling. Mutations cause autosomal recessive intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 0.44
Clinical SummaryLIMD1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 95 VUS of 127 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.44LOEUF
pLI 0.417
Z-score 3.76
OE 0.22 (0.120.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.48Z-score
OE missense 0.93 (0.851.02)
368 obs / 394.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.120.44)
00.351.4
Missense OE0.93 (0.851.02)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 6 / 27.1Missense obs/exp: 368 / 394.7Syn Z: -0.41
DN
0.6065th %ile
GOF
0.73top 25%
LOF
0.51top 25%

The highest-scoring mechanism for this gene is gain-of-function.

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

127 submitted variants in ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS95
Likely Benign6
Benign1
6
Pathogenic
1
Likely Pathogenic
95
VUS
6
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
1
0
1
VUS
0
93
2
0
95
Likely Benign
0
6
0
0
6
Benign
0
0
0
1
1
Total09991109

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

View in ClinVar →

Protein Context — Lollipop Plot

LIMD1 · 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

No active trials found for this gene.

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Clinical Literature
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