STAC3

SH3 and cysteine rich domain 3

Basic information

Region (hg38): 12:57243453-57251188

Links

ENSG00000185482 ∙ NCBI:246329 ∙ OMIM:615521 ∙ HGNC:28423 ∙ Uniprot:Q96MF2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bailey-Bloch congenital myopathy (Strong), mode of inheritance: AR
• Bailey-Bloch congenital myopathy (Supportive), mode of inheritance: AR
• Bailey-Bloch congenital myopathy (Moderate), mode of inheritance: AR
• Bailey-Bloch congenital myopathy (Definitive), mode of inheritance: AR
• Bailey-Bloch congenital myopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital myopathy 13	AR	Musculoskeletal; Pharmacogenomic	Among other findings, individuals have been described with susceptibility to malignant hyperthermia related to anesthesia, and awareness may allow preventive measures	Craniofacial; Musculoskeletal	23736855

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STAC3 gene.

• Bailey-Bloch_congenital_myopathy (230 variants)
• Inborn_genetic_diseases (41 variants)
• not_provided (37 variants)
• not_specified (11 variants)
• STAC3-related_disorder (6 variants)
• Congenital_myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STAC3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000145064.3. 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				49	1	50
missense		1	112	3	1	117
nonsense	2	1	1			4
start loss						0
frameshift	5	2	1			8
splice donor/acceptor (+/-2bp)	1	2	2			5
Total	8	6	116	52	2

Highest pathogenic variant AF is 0.000064427644

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STAC3	protein_coding	protein_coding	ENST00000332782	11	7741

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000172	0.994	125693	0	55	125748	0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.906	180	218	0.827	0.0000122	2405
Missense in Polyphen		76	84.692	0.89737		892
Synonymous	1.26	62	75.9	0.817	0.00000398	652
Loss of Function	2.44	10	22.5	0.445	0.00000122	256

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000814	0.000810
Ashkenazi Jewish	0.00	0.00
East Asian	0.000329	0.000326
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000230	0.000229
Middle Eastern	0.000329	0.000326
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for normal excitation-contraction coupling in skeletal muscle and for normal muscle contraction in response to membrane depolarization. Required for normal Ca(2+) release from the sarcplasmic reticulum, which ultimately leads to muscle contraction. Probably functions via its effects on muscle calcium channels (PubMed:23736855, PubMed:29078335). Increases CACNA1S channel activity, in addition to its role in enhancing the expression of CACNA1S at the cell membrane. Has a redundant role in promoting the expression of the calcium channel CACNA1S at the cell membrane (By similarity). Slows down the inactivation rate of the calcium channel CACNA1C (PubMed:29078335). {ECO:0000250|UniProtKB:Q8BZ71, ECO:0000269|PubMed:23736855, ECO:0000269|PubMed:29078335}.
• Disease: DISEASE: Native American myopathy (NAM) [MIM:255995]: A disease characterized by congenital weakness and arthrogryposis, cleft palate, ptosis, short stature, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia provoked by anesthesia. {ECO:0000269|PubMed:23736855, ECO:0000269|PubMed:29078335}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.420
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.57

Haploinsufficiency Scores

• pHI: 0.162
• hipred: Y
• hipred_score: 0.524
• ghis: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.758

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Stac3
• 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; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; digestive/alimentary 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; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: stac3
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: skeletal muscle contraction;neuromuscular synaptic transmission;intracellular signal transduction;skeletal muscle fiber development;positive regulation of voltage-gated calcium channel activity;positive regulation of protein localization to plasma membrane
• Cellular component: nucleoplasm;cytosol;voltage-gated calcium channel complex;extrinsic component of cytoplasmic side of plasma membrane;sarcolemma
• Molecular function: protein binding;identical protein binding;metal ion binding