MLF1

protein-coding

myeloid leukemia factor 1

Gene summary

This gene encodes an oncoprotein which is thought to play a role in the phenotypic determination of hemopoetic cells. Translocations between this gene and nucleophosmin have been associated with myelodysplastic syndrome and acute myeloid leukemia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2010]

MANE transcript

NM_001369783.1

Inheritance

—

ClinVar variants

U:32B:9

Top phenotype

MLF1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr3:158,571,163-158,607,252

External References & Databases

Ensembl (ENSG00000178053)

Transcript & Mutation Effects

hg38 • Region Span ~36.1 kb

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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 MLF1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 5

MLF1-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001369783.1. 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			1 clinvar	1 clinvar	1 clinvar	3
missense			29 clinvar	3 clinvar	3 clinvar	35
nonsense				1 clinvar		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	32	5	4	41

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001369783.1	RefSeq	NP_001356712.1	8	MANE Select
ENST00000466246.7	Ensembl	ENSP00000417278.2	8	MANE Select
NM_001130156.3	RefSeq	NP_001123628.1	6	Standard
NM_001130157.3	RefSeq	NP_001123629.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transcriptional misregulation in cancer - Homo sapiens (human)

Biological Process

myeloid progenitor cell differentiation
transcription, DNA-templated
regulation of transcription, DNA-templated
cell cycle arrest

Molecular Function

DNA binding
protein binding
protein domain specific binding

Cellular Component

nucleus
cytoplasm
cilium
ciliary basal body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392822
Coding exons: 8
Length: 36090
Individuals with no LoFs: 125621
Homozygous LoFs: 2
Heterozygous LoFs: 118
Defined: 125741
p: 0.000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.587	129	149	0.865	0.00000723	1969
Missense (PolyPhen)		40	45.783	0.87368		632
Synonymous	1.55	33	46.4	0.711	0.00000214	525
Loss of Function	0.839	15	18.9	0.792	0.00000139	213

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0038	0.0036	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00025	0.00024	rare
South Asian	0.00059	0.00059	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in lineage commitment of primary hemopoietic progenitors by restricting erythroid formation and enhancing myeloid formation. Interferes with erythropoietin-induced erythroid terminal differentiation by preventing cells from exiting the cell cycle through suppression of CDKN1B/p27Kip1 levels. Suppresses COP1 activity via CSN3 which activates p53 and induces cell cycle arrest. Binds DNA and affects the expression of a number of genes so may function as a transcription factor in the nucleus. {ECO:0000269|PubMed:15861129}.;
Disease: DISEASE: Note=A chromosomal aberration involving MLF1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with NPM1/NPM. {ECO:0000269|PubMed:8570204}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.986
RVIS EVS: 0.53
RVIS percentile EVS: 80.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.452

Gene Damage Prediction

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