LIN54

Chr 4

lin-54 DREAM MuvB core complex component

Also known as: CXCDC1, JC8.6, MIP120, TCX1

LIN54 encodes a component of the DREAM complex that acts as a sequence-specific DNA-binding protein to regulate cell cycle gene expression, binding to over 800 promoters to repress E2F target genes in G0 phase and activate G2/M genes in S phase. Mutations cause autosomal recessive primordial dwarfism with distinctive facial features and intellectual disability. The gene is highly constrained against loss-of-function mutations, indicating intolerance to haploinsufficiency in the general population.

Summary from RefSeq, UniProt
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0
Active trials
0
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.17
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryLIN54
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.17LOEUF
pLI 1.000
Z-score 5.29
OE 0.05 (0.020.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.70Z-score
OE missense 0.62 (0.560.69)
243 obs / 393.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.020.17)
00.351.4
Missense OE0.62 (0.560.69)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 2 / 36.5Missense obs/exp: 243 / 393.7Syn Z: 0.40
DN
0.2199th %ile
GOF
0.09100th %ile
LOF
0.87top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.17

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

LIN54 · 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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Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗