MLLT3

Chr 9

MLLT3 super elongation complex subunit

Also known as: AF9, YEATS3

MLLT3 encodes a chromatin reader component of the super elongation complex that recognizes acetylated and crotonylated histones to promote RNA polymerase II transcription and maintain hematopoietic stem cell function. Mutations cause autosomal dominant neurodevelopmental disorder with developmental delay, intellectual disability, and behavioral abnormalities. This gene is highly constrained against loss-of-function mutations (pLI 0.999, LOEUF 0.131), consistent with its essential role in transcriptional regulation.

ResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.13
Clinical SummaryMLLT3
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.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.13LOEUF
pLI 1.000
Z-score 4.42
OE 0.00 (0.000.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.90Z-score
OE missense 0.69 (0.610.78)
205 obs / 296.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.13)
00.351.4
Missense OE0.69 (0.610.78)
00.61.4
Synonymous OE1.32
01.21.6
LoF obs/exp: 0 / 22.7Missense obs/exp: 205 / 296.9Syn Z: -2.57
DN
0.2698th %ile
GOF
0.1799th %ile
LOF
0.90top 5%

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

LOFprediction above median · LOEUF 0.13

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

MLLT3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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