GeneBe

MLLT3

protein-coding

MLLT3 super elongation complex subunit, the group of MicroRNA protein coding host genes|YEATS domain containing|Super elongation complex

Gene summary

Enables several functions, including chromatin binding activity; histone H3 reader activity; and histone binding activity. Involved in several processes, including hematopoietic stem cell differentiation; positive regulation of DNA-templated transcription; and regulation of stem cell division. Acts upstream of or within negative regulation of canonical Wnt signaling pathway and positive regulation of Wnt signaling pathway, planar cell polarity pathway. Located in nucleoplasm. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_004529.4

Inheritance

—

ClinVar variants

U:63B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr9:20,341,669-20,622,499

External References & Databases

Ensembl (ENSG00000171843)NCBI Gene (4300)OMIM (159558)HGNC:7136GenCCUniProt (P42568)AlphaFoldClinVar (MLLT3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~280.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MLLT3 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 57
not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004529.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
9
clinvar
 9
missense
58
clinvar
 58
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
5
clinvar
 5
Total00639072
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004529.4RefSeqNP_004520.211MANE Select
ENST00000380338.9EnsemblENSP00000369695.411MANE Select
NM_001286691.2RefSeqNP_001273620.111Standard
ENST00000380321.5EnsemblENSP00000369678.15Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Transcriptional misregulation in cancer - Homo sapiens (human)
  • Gene expression (Transcription)
  • RNA Polymerase II Pre-transcription Events
  • Formation of RNA Pol II elongation complex
  • RNA Polymerase II Transcription

Biological Process

  • regulation of transcription by RNA polymerase II
  • transcription by RNA polymerase II
  • transcription elongation from RNA polymerase II promoter
  • segment specification
  • anterior/posterior pattern specification

Molecular Function

  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • chromatin binding
  • protein binding
  • histone binding
  • lysine-acetylated histone binding

Cellular Component

  • nucleus
  • nucleoplasm
  • chromosome
  • transcription elongation factor complex
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000380338
Coding exons
11
Length
280880
Individuals with no LoFs
125641
Homozygous LoFs
0
Heterozygous LoFs
2
Defined
125643
p
0.00000796
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.902052970.6900.00001413851
Missense (PolyPhen)4599.9950.450021355
Synonymous-2.571401061.320.00000540974
Loss of Function4.42022.70.000.00000104320

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.00000910.0000088rare
South Asian0.0000330.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Chromatin reader component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA (PubMed:20159561, PubMed:20471948, PubMed:25417107, PubMed:27105114, PubMed:27545619). Specifically recognizes and binds acylated histone H3, with a marked preference for histone H3 that is crotonylated (PubMed:25417107, PubMed:27105114, PubMed:27545619). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:25417107, PubMed:27105114, PubMed:27545619). Recognizes and binds histone H3 crotonylated at 'Lys-9' (H3K9cr), and with slightly lower affinity histone H3 crotonylated at 'Lys-18' (H3K18cr) (PubMed:27105114). Also recognizes and binds histone H3 acetylated at 'Lys-9' (H3K9ac), but with lower affinity than crotonylated histone H3 (PubMed:25417107, PubMed:27105114). In the SEC complex, MLLT3 is required to recruit the complex to crotonylated histones (PubMed:27105114, PubMed:27545619). {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:25417107, ECO:0000269|PubMed:27105114, ECO:0000269|PubMed:27545619}.;
Disease
DISEASE: Note=A chromosomal aberration involving MLLT3 is associated with acute leukemias. Translocation t(9;11)(p22;q23) with KMT2A/MLL1. The result is a rogue activator protein. {ECO:0000269|PubMed:10861294, ECO:0000269|PubMed:8506309}.; DISEASE: Note=A chromosomal aberration involving MLLT3 was observed in a patient with neuromotor development delay, cerebellar ataxia and epilepsy. Translocation t(4;9)(q35;p22). {ECO:0000269|PubMed:16001262}.;

Recessive Scores

pRec
0.203

Intolerance Scores

LoFtool
0.0415
RVIS EVS
-0.36
RVIS percentile EVS
28.93

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.903

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.