MEIS2

Chr 15AD

Meis homeobox 2

Also known as: CPCMR, HsT18361, MRG1

This homeobox transcription factor regulates developmental programs and is essential for normal embryonic development. Loss-of-function mutations cause autosomal dominant cleft palate, cardiac defects, and intellectual disability. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the mechanism of disease.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.181 OMIM phenotype
Clinical SummaryMEIS2
🧬
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

LoF intolerant — likely haploinsufficient
LoF Constraint
0.18LOEUF
pLI 0.999
Z-score 4.52
OE 0.04 (0.010.18)
Highly constrained

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

Missense Constraint
2.46Z-score
OE missense 0.59 (0.520.67)
171 obs / 288.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.04 (0.010.18)
00.351.4
Missense OE0.59 (0.520.67)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 1 / 25.7Missense obs/exp: 171 / 288.4Syn Z: -0.24
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongMEIS2-related disorder with cleft palate, cardiac defects, and developmental delayLOFAD
DN
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

Protein Context — Lollipop Plot

MEIS2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →