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

Phenotypes

GenCC

Source: genCC

• spondylocostal dysostosis 2, autosomal recessive (Definitive), mode of inheritance: AR
• spondylocostal dysostosis 2, autosomal recessive (Strong), mode of inheritance: AR
• autosomal recessive spondylocostal dysostosis (Supportive), 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 (30 variants)
• Spondylocostal dysostosis 2, autosomal recessive (3 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	244	4	249
missense			75	6	3	84
nonsense	18	10	7			35
start loss			1			1
frameshift	14	3	12			29
inframe indel			7	3	4	14
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding			11	16	4	31
Total	32	13	114	269	15

Highest pathogenic variant AF is 0.000171

Variants in MESP2

This is a list of pathogenic ClinVar variants found in the MESP2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-89776082-T-C			Benign (Jun 20, 2021)
15-89776088-G-A			Benign (Jun 20, 2021)
15-89776347-G-A		not specified • Spondylocostal dysostosis	Likely benign (Jun 14, 2016)
15-89776358-A-G		not specified	Uncertain significance (Nov 16, 2023)
15-89776361-GC-G			Pathogenic (Mar 03, 2022)
15-89776363-C-T			Likely benign (Sep 27, 2023)
15-89776368-C-A		Spondylocostal dysostosis 2, autosomal recessive	Pathogenic/Likely pathogenic (Apr 12, 2023)
15-89776368-CGCCTCCTCCGCAGA-C			Pathogenic (Nov 24, 2021)
15-89776368-C-CGCCTCCTCCGCAGA			Pathogenic (Dec 21, 2021)
15-89776375-T-A		Spondylocostal dysostosis 2, autosomal recessive	Likely benign (Jul 11, 2023)
15-89776377-C-A			Uncertain significance (Feb 04, 2022)
15-89776378-G-A			Likely benign (Apr 05, 2023)
15-89776378-G-T			Likely benign (Mar 26, 2022)
15-89776381-G-A			Likely benign (Dec 17, 2021)
15-89776387-C-T			Likely benign (Jun 13, 2022)
15-89776390-C-A			Likely benign (Jan 30, 2024)
15-89776393-C-G			Likely benign (Nov 17, 2023)
15-89776397-G-T			Uncertain significance (Oct 01, 2022)
15-89776400-C-G		Inborn genetic diseases	Uncertain significance (Nov 21, 2023)
15-89776404-G-A			Pathogenic (Nov 07, 2021)
15-89776405-G-A		Spondylocostal dysostosis 2, autosomal recessive	Likely pathogenic (Jun 27, 2017)
15-89776405-GA-G		Spondylocostal dysostosis 2, autosomal recessive	Pathogenic (Oct 24, 2023)
15-89776415-C-T			Pathogenic (Feb 08, 2023)
15-89776420-C-A			Likely benign (Dec 04, 2022)
15-89776424-G-A		Spondylocostal dysostosis 2, autosomal recessive • MESP2-related disorder	Likely benign (Jan 25, 2024)

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
0.00000311	0.563	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

Haploinsufficiency Scores

• pHI: 0.108
• hipred: N
• hipred_score: 0.187
• ghis: 0.437

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

Mouse Genome Informatics

• Gene name: Mesp2
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; skeleton phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); muscle phenotype; cellular phenotype; growth/size/body region phenotype

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