MESP2

mesoderm posterior bHLH transcription factor 2, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 15:89760591-89778754

Links

ENSG00000188095 ∙ NCBI:145873 ∙ OMIM:605195 ∙ HGNC:29659 ∙ Uniprot:Q0VG99 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 3 of 3.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
ENST00000341735.5	ENSP00000342392.3	2	yes	-
ENST00000560219.2	ENSP00000452998.1	2	-	-
NM_001039958.2	NP_001035047.1	2	yes	-

Phenotypes

GenCC

Source: genCC

• spondylocostal dysostosis 2, autosomal recessive (Strong), mode of inheritance: AR
• autosomal recessive spondylocostal dysostosis (Supportive), mode of inheritance: AR
• spondylocostal dysostosis 2, autosomal recessive (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondylocostal dysostosis 2, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	15214000; 15122512; 18485326; 20301771

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MESP2 gene.

• not_provided (402 variants)
• Spondylocostal_dysostosis_2,_autosomal_recessive (136 variants)
• Inborn_genetic_diseases (64 variants)
• not_specified (23 variants)
• MESP2-related_disorder (12 variants)
• Spondylocostal_dysostosis_1,_autosomal_recessive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MESP2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001039958.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	259	3	268
missense		1	135	12	4	152
nonsense	22	9	6			37
start loss		1	1			2
frameshift	18	10	12			40
splice donor/acceptor (+/-2bp)			1			1
Total	40	21	161	271	7

Highest pathogenic variant AF is 0.00031590465

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MESP2	protein_coding	protein_coding	ENST00000341735	2	18161

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		124731	0	20	124751	0.0000802

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.187	204	212	0.964	0.0000119	2438
Missense in Polyphen		34	38.671	0.87922		550
Synonymous	-0.0161	103	103	1.00	0.00000656	873
Loss of Function	0.834	10	13.3	0.753	5.88e-7	132

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000672	0.0000646
Ashkenazi Jewish	0.0000995	0.0000993
East Asian	0.000569	0.000557
Finnish	0.00	0.00
European (Non-Finnish)	0.0000660	0.0000618
Middle Eastern	0.000569	0.000557
South Asian	0.0000332	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor with important role in somitogenesis. Defines the rostrocaudal patterning of the somite by participating in distinct Notch pathways. Regulates also the FGF signaling pathway. Specifies the rostral half of the somites. Generates rostro-caudal polarity of somites by down-regulating in the presumptive rostral domain DLL1, a Notch ligand. Participates in the segment border formation by activating in the anterior presomitic mesoderm LFNG, a negative regulator of DLL1-Notch signaling. Acts as a strong suppressor of Notch activity. Together with MESP1 is involved in the epithelialization of somitic mesoderm and in the development of cardiac mesoderm.
• Disease: DISEASE: Spondylocostal dysostosis 2, autosomal recessive (SCDO2) [MIM:608681]: A condition of variable severity associated with vertebral and rib segmentation defects. The main skeletal malformations include fusion of vertebrae, hemivertebrae, fusion of certain ribs, and other rib malformations. Deformity of the chest and spine (severe scoliosis, kyphoscoliosis and lordosis) is a natural consequence of the malformation and leads to a dwarf- like appearance. As the thorax is small, infants frequently have respiratory insufficiency and repeated respiratory infections resulting in life-threatening complications in the first year of life. {ECO:0000269|PubMed:15122512}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cardiac Progenitor Differentiation;Gene regulatory network modelling somitogenesis (Consensus)

Recessive Scores

• pRec: 0.141

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.125

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: mespab
• Affected structure: determination of heart left/right asymmetry
• Phenotype tag: abnormal
• Phenotype quality: decreased efficacy

Gene ontology

• Biological process: mesoderm formation;somitogenesis;heart morphogenesis;Notch signaling pathway;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;protein dimerization activity