MEIS2

Chr 15

Meis homeobox 2

Also known as: CPCMR, HsT18361, MRG1

NCBI Gene: 4212 ENSG00000134138 UniProt: O14770

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.18

Clinical Summary— MEIS2

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Gene-Disease Validity (ClinGen)

syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.

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ClinVar Variants

45 unique Pathogenic / Likely Pathogenic· 110 VUS of 236 total submissions

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Clinical Trials

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

Explore recent and relevant literature in Research Assistant →

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GeneReview available — MEIS2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.04 (0.01–0.18)

0≤0.351.4

Missense OE?0.59 (0.52–0.67)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

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

This gene — mechanism propensity

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 · 60% of P/LP variants are LoF · LOEUF 0.18 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFMild developmental disability and autism spectrum disorder diagnosed in childhood were also considered to be consequences of MEIS2 haploinsufficiency.1

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

References

1.PMID 28736618 ↗

ClinVar Variant Classifications

236 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19

Likely Pathogenic26

VUS110

Likely Benign52

Benign13

Conflicting1

Pathogenic

Likely Pathogenic

110

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	16	2	1	0	19
Likely Pathogenic	11	15	0	0	26
VUS	7	90	10	3	110
Likely Benign	0	5	13	34	52
Benign	0	6	3	4	13
Conflicting	—				1
Total	34	118	27	41	221

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

24 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap MEIS2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →