MLLT10

protein-coding

MLLT10 histone lysine methyltransferase DOT1L cofactor, the group of PHD finger proteins

Gene summary

This gene encodes a transcription factor and has been identified as a partner gene involved in several chromosomal rearrangements resulting in various leukemias. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2010]

MANE transcript

NM_001195626.3

Inheritance

—

ClinVar variants

U:120B:16

Top phenotype

MLLT10-related disorder

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr10:21,524,646-21,743,630

External References & Databases

Ensembl (ENSG00000078403)

Transcript & Mutation Effects

hg38 • Region Span ~219.0 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 MLLT10 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 109

MLLT10-related disorderTotal: 12

not providedTotal: 7

Acute myeloid leukemiaTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001195626.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	11 clinvar	1 clinvar	16
missense			111 clinvar	4 clinvar		115
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	120	15	1	136

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001195626.3	RefSeq	NP_001182555.1	22	MANE Select
ENST00000307729.12	Ensembl	ENSP00000307411.7	22	MANE Select
NM_001195627.2	RefSeq	NP_001182556.1	4	Standard
NM_001195628.2	RefSeq	NP_001182557.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mllt10	Danio rerio	Structure: intestinal villus Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

mllt10

Danio rerio

Structure: intestinal villus

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of transcription by RNA polymerase II

Molecular Function

DNA binding
chromatin binding
DNA-binding transcription factor activity
protein binding
nucleosome binding

Cellular Component

nucleus
nucleoplasm
cytosol
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000307729
Coding exons: 22
Length: 209466
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125748
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.60	447	553	0.809	0.0000267	6902
Missense (PolyPhen)		109	190.46	0.57229		2405
Synonymous	-1.19	218	197	1.11	0.00000949	2105
Loss of Function	6.43	5	57.7	0.0867	0.00000292	698

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000089	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000099	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probably involved in transcriptional regulation. In vitro or as fusion protein with KMT2A/MLL1 has transactivation activity. Binds to cruciform DNA. In cells, binding to unmodified histone H3 regulates DOT1L functions including histone H3 'Lys-79' dimethylation (H3K79me2) and gene activation (PubMed:26439302). {ECO:0000269|PubMed:17868029, ECO:0000269|PubMed:26439302}.;
Disease: DISEASE: Note=A chromosomal aberration involving MLLT10 is associated with diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with PICALM.;

Recessive Scores

pRec: 0.177

Intolerance Scores

LoFtool: 0.336
RVIS EVS: -1.28
RVIS percentile EVS: 5.13

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.912

Gene Damage Prediction

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