MEIS3

protein-coding

Meis homeobox 3, the group of TALE class homeoboxes and pseudogenes

Gene summary

This gene encodes a homeobox protein and probable transcriptional regulator. The orthologous protein in mouse controls expression of 3-phosphoinositide dependent protein kinase 1, which promotes survival of pancreatic beta-cells. [provided by RefSeq, Sep 2016]

MANE transcript

NM_001301059.2

Inheritance

—

ClinVar variants

U:78B:6

Top phenotype

Abnormality of neuronal migration

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr19:47,403,124-47,419,527

External References & Databases

Ensembl (ENSG00000105419)

Transcript & Mutation Effects

hg38 • Region Span ~16.4 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 MEIS3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 82

not providedTotal: 2

Abnormality of neuronal migrationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001301059.2. 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
missense			76 clinvar	4 clinvar	1 clinvar	81
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	78	4	2	84

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 79 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001301059.2	RefSeq	NP_001287988.1	12	MANE Select
ENST00000558555.6	Ensembl	ENSP00000454073.1	12	MANE Select
NM_001009813.3	RefSeq	NP_001009813.1	12	Standard
NM_001346148.2	RefSeq	NP_001333077.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of transcription by RNA polymerase II
positive regulation of protein kinase B signaling
negative regulation of apoptotic signaling pathway

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
chromatin binding
sequence-specific DNA binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000561293
Coding exons: 12
Length: 16400
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 50
Defined: 125748
p: 0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.165	243	250	0.971	0.0000138	2704
Missense (PolyPhen)		65	74.867	0.8682		886
Synonymous	-0.544	113	106	1.07	0.00000643	842
Loss of Function	1.53	17	25.3	0.672	0.00000140	260

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.00047	0.00046	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional regulator which directly modulates PDPK1 expression, thus promoting survival of pancreatic beta-cells. Also regulates expression of NDFIP1, BNIP3, and CCNG1. {ECO:0000250|UniProtKB:P97368}.;

Intolerance Scores

LoFtool: 0.154
RVIS EVS: -0.13
RVIS percentile EVS: 43.91

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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