SPEG

striated muscle enriched protein kinase, the group of I-set domain containing|Myosin light chain kinase family

Basic information

Region (hg38): 2:219434843-219493629

Previous symbols: [ "APEG1" ]

Links

ENSG00000072195

∙ NCBI:10290 ∙ OMIM:615950 ∙ HGNC:16901 ∙ Uniprot:Q15772 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

myopathy, centronuclear, 5 (Definitive), mode of inheritance: AR
autosomal recessive centronuclear myopathy (Supportive), mode of inheritance: AR
myopathy, centronuclear, 5 (Strong), mode of inheritance: AR
myopathy, centronuclear, 5 (Definitive), mode of inheritance: AR
myopathy, centronuclear, 5 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Centronuclear myopathy 5	AR	Cardiovascular	The condition may include cardiomyopathy, and recognition may allow early management, which has been described as effectve in affected individuals	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	25087613

ClinVar

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

not_provided (1674 variants)
Inborn_genetic_diseases (502 variants)
Myopathy,_centronuclear,_5 (143 variants)
SPEG-related_disorder (84 variants)
not_specified (14 variants)
SPEG-related_congenital_myopathy (2 variants)
Congenital_myopathy (1 variants)
Autosomal_dominant_centronuclear_myopathy (1 variants)
Myopathy,_centronuclear,_2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPEG gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005876.5. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			12 clinvar	620 clinvar	26 clinvar	658
missense	1 clinvar		1040 clinvar	55 clinvar	17 clinvar	1113
nonsense	10 clinvar	7 clinvar	2 clinvar			19
start loss						0
frameshift	19 clinvar	7 clinvar	1 clinvar			27
splice donor/acceptor (+/-2bp)	1 clinvar	3 clinvar	9 clinvar			13
Total	31	17	1064	675	43

Highest pathogenic variant AF is 0.00001303938

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPEG	protein_coding	protein_coding	ENST00000312358	41	63442

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.923	0.0768	124755	0	60	124815	0.000240

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.78	1541	1.88e+3	0.820	0.000123	20326
Missense in Polyphen		555	775.27	0.71588		8341
Synonymous	1.01	799	836	0.956	0.0000553	7364
Loss of Function	8.24	27	127	0.212	0.00000716	1372

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00145	0.00143
Ashkenazi Jewish	0.000102	0.0000993
East Asian	0.000168	0.000167
Finnish	0.0000946	0.0000928
European (Non-Finnish)	0.000213	0.000185
Middle Eastern	0.000168	0.000167
South Asian	0.000263	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Isoform 3 may have a role in regulating the growth and differentiation of arterial smooth muscle cells.;
Disease: DISEASE: Myopathy, centronuclear, 5 (CNM5) [MIM:615959]: A form of centronuclear myopathy, a congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. CNM5 features include severe neonatal hypotonia with respiratory insufficiency, difficulty feeding, and delayed motor development. Some patients die in infancy, and some develop dilated cardiomyopathy. {ECO:0000269|PubMed:25087613}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.128

Intolerance Scores

loftool: 0.507
rvis_EVS: -0.06
rvis_percentile_EVS: 48.92

Haploinsufficiency Scores

pHI: 0.411
hipred: Y
hipred_score: 0.667
ghis: 0.540

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.631

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

Gene name: Speg
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); hematopoietic system 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); respiratory system phenotype; immune system phenotype; muscle phenotype;

Gene ontology

Biological process: protein phosphorylation;muscle organ development;negative regulation of cell population proliferation;muscle cell differentiation;cardiovascular system development
Cellular component: nucleus
Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding