MESP1

protein-coding

mesoderm posterior bHLH transcription factor 1, the group of Basic helix-loop-helix proteins

Gene summary

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. Located in nucleoplasm. Implicated in myocardial infarction. Biomarker of diabetic retinopathy. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_018670.4

Inheritance

ClinVar variants

U:108B:36

Top phenotype

MESP1-related disorder

gnomAD constraint

pLI —, LoF o/e 1.68

Max pathogenic AF

—

Genomic locus

chr15:89,749,875-89,751,249

External References & Databases

Ensembl (ENSG00000166823)

Transcript & Mutation Effects

hg38 • Region Span ~1.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital heart diseaseMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0005453

Submitter: ClinGen

*MESP1* was first reported in relation to autosomal dominant congenital heart disease in 2013 (Lahm P et al., PMID:24056064). Four variants (missense, nonsense, frameshift) that have been reported in four probands in two publications (PMID:26694203, 28677747) are included in this curation. This gene-disease relationship is also supported by functional alteration, mouse model, and expression evidence. (PMID: 36413948, 10393122). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date September 9th 2024 (SOP Version 11).

congenital heart diseaseMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0005453

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MESP1 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 84

not specifiedTotal: 82

MESP1-related disorderTotal: 16

Congenital heart diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018670.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				17 clinvar	5 clinvar	22
missense			103 clinvar	6 clinvar	7 clinvar	116
nonsense			3 clinvar			3
start loss						0
frameshift			2 clinvar		1 clinvar	3
splice donor/acceptor (+/-2bp)						0
Total	0	0	108	23	13	144

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018670.4	RefSeq	NP_061140.1	2	MANE Select
ENST00000300057.5	Ensembl	ENSP00000300057.4	2	MANE Select
ENST00001137323.1	Ensembl	ENSP00000805379.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mespbb	Danio rerio	Structure: determination of heart left/right asymmetry Quality: decreased efficacy abnormal

Gene / Model

Organism

Observed Phenotype

mespbb

Danio rerio

Structure: determination of heart left/right asymmetry

Quality: decreased efficacy

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cardiac Progenitor Differentiation

Biological Process

mesoderm formation
somitogenesis
heart looping
heart morphogenesis
secondary heart field specification

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription factor activity
enhancer binding
transcription regulatory region DNA binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000300057
Coding exons: 2
Length: 2650
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.348	74	82.9	0.892	0.00000391	1552
Missense (PolyPhen)		25	30.275	0.82576		500
Synonymous	0.0186	39	39.1	0.996	0.00000192	591
Loss of Function	-1.09	5	2.97	1.68	1.28e-7	55

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor. Plays a role in the epithelialization of somitic mesoderm and in the development of cardiac mesoderm. Defines the rostrocaudal patterning of the somites by participating in distinct Notch pathways (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.123

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.127

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium