MESP1

Chr 15

mesoderm posterior bHLH transcription factor 1

Also known as: bHLHc5

NCBI Gene: 55897 ENSG00000166823 UniProt: Q9BRJ9 OMIM: 608689

MESP1 encodes a transcription factor that regulates heart development and somite patterning during embryogenesis. The gene shows low constraint to loss-of-function variation (pLI ~0, LOEUF 1.94), and while it has been implicated in myocardial infarction susceptibility, definitive Mendelian disease associations have not been established in the provided data.

OMIM ResearchSummary from RefSeq, UniProt

Enables DNA-binding transcription factor activity and transcription cis-regulatory region binding activity. Involved in several processes, including endothelial cell differentiation; heart development; and positive regulation of transcription by RNA polymerase II. Predicted to be located in chromatin. Predicted to be active in nucleus. Implicated in myocardial infarction. Biomarker of diabetic retinopathy. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.94

Clinical Summary— MESP1

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Gene-Disease Validity (ClinGen)

congenital heart disease · ADModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

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

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ClinVar Variants

144 VUS of 199 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.94LOEUF

pLI 0.000

Z-score -1.09

OE 1.68 (0.76–1.94)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.35Z-score

OE missense 0.89 (0.74–1.08)

74 obs / 82.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.68 (0.76–1.94)

0≤0.351.4

Missense OE?0.89 (0.74–1.08)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 5 / 3.0Missense obs/exp: 74 / 82.9Syn Z: 0.02

ClinVar Variant Classifications

199 submitted variants in ClinVar

ClinVar

Classification Summary

VUS144

Likely Benign25

Benign20

Conflicting3

144

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	5	139	0	0	144
Likely Benign	1	5	2	17	25
Benign	1	11	0	8	20
Conflicting	—				3
Total	7	155	2	25	192

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 MESP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →