MEIS2

Meis homeobox 2, the group of TALE class homeoboxes and pseudogenes|MicroRNA protein coding host genes

Basic information

Region (hg38): 15:36889204-37101299

Links

ENSG00000134138 ∙ NCBI:4212 ∙ OMIM:601740 ∙ HGNC:7001 ∙ Uniprot:O14770 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies (Moderate), mode of inheritance: AD
• cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies (Definitive), mode of inheritance: AD
• syndromic intellectual disability (Definitive), mode of inheritance: AD
• neurodevelopmental disorder (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cleft palate, cardiac defects, and impaired intellectual development	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early identifcation and management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	24678003; 25712757; 26561393; 27225850

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MEIS2 gene.

• Cardiac_malformation,_cleft_lip/palate,_microcephaly,_and_digital_anomalies (100 variants)
• not_provided (49 variants)
• Inborn_genetic_diseases (46 variants)
• MEIS2-related_disorder (14 variants)
• Cleft_palate (2 variants)
• not_specified (2 variants)
• Cleft_lip/palate (1 variants)
• Syndromic_intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MEIS2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000170675.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	29	5	37
missense	2	13	72	6	5	98
nonsense	9	2	1			12
start loss						0
frameshift	4	5	3			12
splice donor/acceptor (+/-2bp)	4	2	1			7
Total	19	22	80	35	10

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MEIS2	protein_coding	protein_coding	ENST00000561208	12	212099

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000617	125642	0	5	125647	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.46	171	288	0.593	0.0000145	3167
Missense in Polyphen		19	76.782	0.24745		928
Synonymous	-0.239	113	110	1.03	0.00000657	901
Loss of Function	4.52	1	25.7	0.0389	0.00000126	284

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000187	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in transcriptional regulation. Binds to HOX or PBX proteins to form dimers, or to a DNA-bound dimer of PBX and HOX proteins and thought to have a role in stabilization of the homeoprotein-DNA complex. Isoform 3 is required for the activity of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element; MEIS2 is not involved in complex DNA-binding. Probably in complex with PBX1, is involved in transcriptional regulation by KLF4. Isoform 3 and isoform 4 can bind to a EPHA8 promoter sequence containing the DNA motif 5'-CGGTCA-3'; in cooperation with a PBX protein (such as PBX2) is proposed to be involved in the transcriptional activation of EPHA8 in the developing midbrain. May be involved in regulation of myeloid differentiation. Can bind to the DNA sequence 5'-TGACAG-3'in the activator ACT sequence of the D(1A) dopamine receptor (DRD1) promoter and activate DRD1 transcription; isoform 5 cannot activate DRD1 transcription. {ECO:0000269|PubMed:10764806, ECO:0000269|PubMed:11279116, ECO:0000269|PubMed:21746878}.
• Disease: DISEASE: Cleft palate, cardiac defects, and mental retardation (CPCMR) [MIM:600987]: An autosomal dominant disease characterized by multiple congenital malformations, mild-to-severe intellectual disability with poor speech, and delayed psychomotor development. Congenital malformations include heart defects, cleft lip/palate, distally-placed thumbs and toes, and cutaneous syndactyly between the second and third toes. {ECO:0000269|PubMed:24678003, ECO:0000269|PubMed:25712757, ECO:0000269|PubMed:27225850}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.163

Intolerance Scores

• loftool: 0.0910
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.53

Haploinsufficiency Scores

• pHI: 0.621
• hipred: Y
• hipred_score: 0.768
• ghis: 0.548

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.977

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Meis2
• Phenotype: vision/eye phenotype; digestive/alimentary phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; liver/biliary system phenotype; embryo phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); craniofacial phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: meis2a
• Affected structure: cranial cartilage
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;eye development;transcription by RNA polymerase II;visual learning;response to mechanical stimulus;pancreas development;negative regulation of myeloid cell differentiation;positive regulation of mitotic cell cycle;positive regulation of transcription by RNA polymerase II;response to growth factor;positive regulation of cardiac muscle myoblast proliferation
• Cellular component: nucleus;perinuclear region of cytoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;transcription coregulator activity;transcription corepressor activity;protein binding;transcription factor binding