MEIS2

Chr 15AD

Meis homeobox 2

Also known as: CPCMR, HsT18361, MRG1

NCBI Gene: 4212 ENSG00000134138 UniProt: O14770

This gene encodes a homeobox protein belonging to the TALE ('three amino acid loop extension') family of homeodomain-containing proteins. TALE homeobox proteins are highly conserved transcription regulators, and several members have been shown to be essential contributors to developmental programs. Multiple transcript variants encoding distinct isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Cleft palate, cardiac defects, and impaired intellectual developmentMIM #600987

Active trials

Pathogenic / LP

ClinVar variants

Pubs (1 yr)

2.5

Missense Z

0.18

LOEUF· LoF intolerant

Clinical Summary— MEIS2

🧬

Gene-Disease Validity (ClinGen)

syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

💊

Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

📖

GeneReview available — MEIS2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint

0.18LOEUF

pLI 0.999

Z-score 4.52

OE 0.04 (0.01–0.18)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint

2.46Z-score

OE missense 0.59 (0.52–0.67)

171 obs / 288.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios

LoF OE0.04 (0.01–0.18)

0≤0.351.4

Missense OE0.59 (0.52–0.67)

0≤0.61.4

Synonymous OE1.03

0≤1.21.6

LoF obs/exp: 1 / 25.7Missense obs/exp: 171 / 288.4Syn Z: -0.24

LOF

Badonyi & Marsh 2024 ↗

0.4091th %ile

GOF

0.2895th %ile

LOF

0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.18

Literature Evidence

LOFMild developmental disability and autism spectrum disorder diagnosed in childhood were also considered to be consequences of MEIS2 haploinsufficiency.PMID:28736618

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

MEIS2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MEIS2-related disorder with cleft palate, cardiac defects, and developmental delay

strong

ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure

Dev. Disorders

G2P ↗

splice acceptor variantsplice donor variantframeshift variantstop gainedmissense variantinframe deletionwhole partial gene deletionwhole partial gene duplication

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org