MESP2

Chr 15AR

mesoderm posterior bHLH transcription factor 2

Also known as: SCDO2, bHLHc6

NCBI Gene: 145873 ENSG00000188095 UniProt: Q0VG99 OMIM: 605195

This gene encodes a bHLH transcription factor that defines the rostrocaudal patterning of somites during embryonic development by regulating Notch and FGF signaling pathways and participates in epithelialization of somitic mesoderm and cardiac mesoderm development. Mutations cause autosomal recessive spondylocostal dysostosis 2, a skeletal disorder affecting vertebral and rib development. The gene shows low constraint against loss-of-function variants (pLI near 0), consistent with the recessive inheritance pattern where biallelic mutations are required for disease.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the bHLH family of transcription factors and plays a key role in defining the rostrocaudal patterning of somites via interactions with multiple Notch signaling pathways. This gene is expressed in the anterior presomitic mesoderm and is downregulated immediately after the formation of segmented somites. This gene also plays a role in the formation of epithelial somitic mesoderm and cardiac mesoderm. Mutations in the MESP2 gene cause autosomal recessive spondylocostal dystosis 2 (SCD02). [provided by RefSeq, Oct 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.281 OMIM phenotype

Clinical Summary— MESP2

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

78 unique Pathogenic / Likely Pathogenic· 183 VUS of 579 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — MESP2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.28LOEUF

pLI 0.000

Z-score 0.83

OE 0.75 (0.46–1.28)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.19Z-score

OE missense 0.96 (0.86–1.08)

204 obs / 211.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.75 (0.46–1.28)

0≤0.351.4

Missense OE?0.96 (0.86–1.08)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 10 / 13.3Missense obs/exp: 204 / 211.7Syn Z: -0.02

ClinVar Variant Classifications

579 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35

Likely Pathogenic43

VUS183

Likely Benign284

Benign17

Conflicting14

Pathogenic

Likely Pathogenic

183

VUS

284

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	34	0	1	0	35
Likely Pathogenic	42	1	0	0	43
VUS	19	142	16	6	183
Likely Benign	0	12	20	252	284
Benign	0	8	5	4	17
Conflicting	—				14
Total	95	163	42	262	576

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

View in ClinVar →

39 pathogenic / likely-pathogenic (of 47) ClinVar copy-number / structural variants overlap MESP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →