MESP2

Chr 15

mesoderm posterior bHLH transcription factor 2

Also known as: SCDO2, bHLHc6

NCBI Gene: 145873 ENSG00000188095 UniProt: Q0VG99

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 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 ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpondylocostal dysostosis 2, autosomal recessive

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.28

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — MESP2

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

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

Background carrier burden — how many people carry a rare variant somewhere in MESP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

713 rare PASS variants

Rare truncating (LoF)

1 in 230

106 rare PASS variants

Rare synonymous (reference)

1 in 220

326 rare PASS variants

Rare missense and truncating variants are carried at similar rates in MESP2; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 270
South Asian	~43k	1 in 84	1 in 390
Remaining (unassigned)	~30k	1 in 78	1 in 330
European (Finnish)	~27k	1 in 320	1 in 380
Admixed American	~22k	1 in 110	1 in 410
African / African American	~21k	1 in 93	1 in 300
East Asian	~20k	1 in 140	1 in 450
Ashkenazi Jewish	~13k	1 in 400	1 in 390
Middle Eastern	~2,884	1 in 67	1 in 520

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓