MLLT10

Chr 10ADSomatic

MLLT10 histone lysine methyltransferase DOT1L cofactor

Also known as: AF10

This protein functions as a transcription factor that regulates gene expression by binding to histones and DNA, and controls histone methylation through DOT1L interactions. Mutations cause acute myeloid leukemia, typically through somatic chromosomal rearrangements that create fusion proteins. The gene is highly constrained against loss-of-function variants in the general population, and inheritance follows an autosomal dominant pattern when germline mutations are involved.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Leukemia, acute myeloidMIM #601626
ADSomatic
1
Active trials
34
Pubs (1 yr)
10
P/LP submissions
0%
P/LP missense
0.18
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryMLLT10
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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ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 109 VUS of 169 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.18LOEUF
pLI 1.000
Z-score 6.43
OE 0.09 (0.040.18)
Highly constrained

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

Missense Constraint
1.60Z-score
OE missense 0.81 (0.750.87)
447 obs / 552.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.040.18)
00.351.4
Missense OE0.81 (0.750.87)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 5 / 57.7Missense obs/exp: 447 / 552.9Syn Z: -1.19
DN
0.2997th %ile
GOF
0.2597th %ile
LOF
0.83top 5%

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

LOFprediction above median · LOEUF 0.18

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

169 submitted variants in ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS109
Likely Benign17
Benign6
9
Pathogenic
1
Likely Pathogenic
109
VUS
17
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
1
0
1
VUS
0
105
4
0
109
Likely Benign
0
6
3
8
17
Benign
0
1
3
2
6
Total01122010142

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

View in ClinVar →

Protein Context — Lollipop Plot

MLLT10 · protein map & ClinVar variants

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

Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗