MLLT3

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

Basic information

Region (hg38): 9:20341668-20622499

Links

ENSG00000171843 ∙ NCBI:4300 ∙ OMIM:159558 ∙ HGNC:7136 ∙ Uniprot:P42568 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MLLT3 gene.

• Inborn genetic diseases (17 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MLLT3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	1	5
missense			17			17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	17	4	1

Variants in MLLT3

This is a list of pathogenic ClinVar variants found in the MLLT3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-20354863-C-T		not specified	Uncertain significance (Jun 11, 2021)
9-20360768-G-C		not specified	Uncertain significance (Jul 26, 2022)
9-20360785-T-C		not specified	Uncertain significance (Dec 06, 2022)
9-20360786-G-A		not specified	Uncertain significance (Nov 14, 2023)
9-20363486-G-C		not specified	Uncertain significance (Dec 22, 2023)
9-20363492-C-T		not specified	Uncertain significance (Sep 23, 2023)
9-20363506-G-A		not specified	Uncertain significance (Feb 22, 2023)
9-20363575-T-C		not specified	Uncertain significance (Apr 11, 2023)
9-20363593-G-T		not specified	Uncertain significance (Apr 07, 2022)
9-20363596-C-T		not specified	Uncertain significance (Jul 16, 2021)
9-20413761-T-C		not specified	Uncertain significance (May 25, 2023)
9-20413788-G-A		not specified	Uncertain significance (Oct 12, 2022)
9-20413794-G-A		not specified	Uncertain significance (Aug 02, 2021)
9-20413813-A-G		not specified	Uncertain significance (Oct 26, 2022)
9-20413912-T-C		not specified	Uncertain significance (Jun 12, 2023)
9-20413965-G-A		not specified	Uncertain significance (Aug 01, 2022)
9-20413992-G-A		not specified	Uncertain significance (Apr 27, 2022)
9-20414108-T-G		not specified	Uncertain significance (Sep 29, 2023)
9-20414151-G-A		not specified	Uncertain significance (Feb 21, 2024)
9-20414163-G-T		not specified	Uncertain significance (Aug 04, 2021)
9-20414306-G-A			Likely benign (Nov 01, 2022)
9-20414307-C-G		not specified	Uncertain significance (Jun 26, 2023)
9-20414310-C-T		not specified	Uncertain significance (Feb 27, 2023)
9-20414357-G-A			Likely benign (Aug 01, 2023)
9-20414378-A-G			Benign (Nov 30, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MLLT3	protein_coding	protein_coding	ENST00000380338	11	280880

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000361	125641	0	2	125643	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.90	205	297	0.690	0.0000141	3851
Missense in Polyphen		45	99.995	0.45002		1355
Synonymous	-2.57	140	106	1.32	0.00000540	974
Loss of Function	4.42	0	22.7	0.00	0.00000104	320

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000914	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000328	0.0000327
Other	0.00	0.00

dbNSFP

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}.
• Pathway: 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;RNA Polymerase II Transcription Elongation (Consensus)

Recessive Scores

• pRec: 0.203

Intolerance Scores

• loftool: 0.0415
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.93

Haploinsufficiency Scores

• pHI: 0.514
• hipred: Y
• hipred_score: 0.825
• ghis: 0.621

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.903

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mllt3
• Phenotype: hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; embryo phenotype; immune system phenotype; skeleton phenotype; growth/size/body region phenotype

Gene ontology

• 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;positive regulation of transcription, DNA-templated;negative regulation of canonical Wnt signaling pathway;positive regulation of Wnt signaling pathway, planar cell polarity pathway
• Cellular component: nucleus;nucleoplasm;chromosome;transcription elongation factor complex;extracellular exosome
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;chromatin binding;protein binding;histone binding;lysine-acetylated histone binding;modification-dependent protein binding