STAC3 (SH3 and cysteine rich domain 3)

Gene

• Entrez ID: 246329
• Gene name: SH3 and cysteine rich domain 3
• Gene symbol: STAC3
• Synonyms (NCBI Gene): CMYO13, CMYP13, MYPBB, NAM
• Chromosome: 12
• Chromosome location: 12q13.3
• Summary: The protein encoded by this gene is a component of the excitation-contraction coupling machinery of muscles. This protein is a member of the Stac gene family and contains an N-terminal cysteine-rich domain and two SH3 domains. Mutations in this gene are a

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs140291094	C>G,T	Pathogenic	Missense variant, non coding transcript variant, stop gained, coding sequence variant
rs371720347	T>A,C	Likely-pathogenic, pathogenic	Missense variant, stop gained, non coding transcript variant, coding sequence variant
rs751033943	T>A	Uncertain-significance, pathogenic	Intron variant
rs773050511	AGAG>-	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs779483367	C>A,G,T	Pathogenic, uncertain-significance	Splice acceptor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1394356	hsa-miR-3160-5p	CLIP-seq
MIRT1394357	hsa-miR-3180-5p	CLIP-seq
MIRT1394358	hsa-miR-4267	CLIP-seq
MIRT2340472	hsa-miR-1249	CLIP-seq
MIRT2340473	hsa-miR-4290	CLIP-seq
MIRT2340474	hsa-miR-4469	CLIP-seq
MIRT2340475	hsa-miR-4655-3p	CLIP-seq
MIRT2466184	hsa-miR-150	CLIP-seq
MIRT2466185	hsa-miR-3183	CLIP-seq
MIRT2466186	hsa-miR-3667-3p	CLIP-seq
MIRT2466187	hsa-miR-3685	CLIP-seq
MIRT2466188	hsa-miR-4274	CLIP-seq
MIRT2466189	hsa-miR-4530	CLIP-seq
MIRT2466190	hsa-miR-4667-3p	CLIP-seq
MIRT2466191	hsa-miR-4713-5p	CLIP-seq
MIRT2466192	hsa-miR-4723-3p	CLIP-seq
MIRT2466193	hsa-miR-532-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003009	Process	Skeletal muscle contraction	IBA
GO:0003009	Process	Skeletal muscle contraction	IMP	23736855
GO:0005515	Function	Protein binding	IPI	16189514, 21516116, 25416956, 26871637, 29892012, 31515488, 32296183, 32814053, 36950384
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0005891	Component	Voltage-gated calcium channel complex	IEA
GO:0005891	Component	Voltage-gated calcium channel complex	ISS
GO:0007274	Process	Neuromuscular synaptic transmission	IMP	23736855
GO:0008270	Function	Zinc ion binding	IEA
GO:0009898	Component	Cytoplasmic side of plasma membrane	IEA
GO:0009898	Component	Cytoplasmic side of plasma membrane	ISS
GO:0016020	Component	Membrane	IEA
GO:0030315	Component	T-tubule	IEA
GO:0042383	Component	Sarcolemma	IEA
GO:0042802	Function	Identical protein binding	IPI	16189514, 25416956, 32296183
GO:0045202	Component	Synapse	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0048741	Process	Skeletal muscle fiber development	IEA
GO:1901387	Process	Positive regulation of voltage-gated calcium channel activity	ISS
GO:1903078	Process	Positive regulation of protein localization to plasma membrane	IBA
GO:1903078	Process	Positive regulation of protein localization to plasma membrane	IEA
GO:1903078	Process	Positive regulation of protein localization to plasma membrane	ISS

Other IDs

• MIM: 615521
• HGNC: 28423
• e!Ensembl: ENSG00000185482

Protein

• UniProt ID: Q96MF2
• Protein name: SH3 and cysteine-rich domain-containing protein 3
• Protein 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
• PDB: 2DB6, 6B29, 6UY7, 6UY8, 6UY9
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00130	C1_1	90 → 144	Phorbol esters/diacylglycerol binding domain (C1 domain)	Domain
  PF16664	STAC2_u1	146 → 253		Disordered
  PF00018	SH3_1	253 → 298	SH3 domain	Domain
  PF07653	SH3_2	310 → 364	Variant SH3 domain	Domain

• Sequence:

  MTEKEVLESPKPSFPAETRQSGLQRLKQLLRKGSTGTKEMELPPEPQANGEAVGAGGGPI
  YYIYEEEEEEEEEEEEPPPEPPKLVNDKPHKFKDHFFKKPKFCDVCARMIVLNNKFGLRC
  KNCKTNIHEHCQSYVEMQRCFGKIPPGFHRAYSSPLYSNQQYACVKDLSAANRNDPVFET
  LRTGVIMANKERKKGQADKKNPVAAMMEEEPESARPEEGKPQDGNPEGDKKAEKKTPDDK
  HKQPGFQQSHYFVALYRFKALEKDDLDFPPGEKITVIDDSNEEWWRGKIGEKVGFFPPNF
  IIRVRAGERVHRVTRSFVGNREIGQITLKKDQIVVQKGDEAGGYVKVYTGRKVGLFPTDF
  LEEI

• Sequence length: 364

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Bailey-Bloch congenital myopathy	Pathogenic; Likely pathogenic	rs774555559, rs780801708, rs112253539, rs2548121140, rs1269908637, rs2548119843, rs371720347, rs1555194630, rs773050511, rs1202215410, rs779483367, rs140291094	RCV001386128 RCV001824231 RCV002944314 RCV003582707 RCV003740905 RCV003812039 RCV000677630 RCV000545173 RCV000677632 RCV000700459 RCV000851531 RCV000074400	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Congenital myopathy	Likely pathogenic	rs777740921	RCV004018271	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Gastric cancer	Likely pathogenic; Pathogenic	rs371720347	RCV005899688	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
STAC3-related disorder	Likely pathogenic; Pathogenic	rs140291094	RCV004757959	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL MYOPATHY 13	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEPATOMEGALY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NATIVE AMERICAN MYOPATHY	—	CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acquired Kyphoscoliosis	Acquired Kyphoscoliosis	BEFREE	28777491		★☆☆☆☆ Found in Text Mining only
Acquired Kyphoscoliosis	Acquired Kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Arrhythmias Cardiac	Cardiac arrhythmias	Pubtator	35414440	Associate	★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis	Pubtator	33060286, 33820833	Associate	★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis multiplex congenita	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharophimosis	Blepharophimosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	BEFREE	28777491		★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Bone Diseases Developmental	Bone disease	Pubtator	33820833	Associate	★☆☆☆☆ Found in Text Mining only
Brachycephaly	Brachycephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	35120484, 37908350	Associate	★☆☆☆☆ Found in Text Mining only
Cerebrovascular Disorders	Cerebrovascular Disorders	BEFREE	28606562		★☆☆☆☆ Found in Text Mining only
Cleft Palate	Cleft palate	Pubtator	28777491	Associate	★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Camptodactyly	Congenital Camptodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital clubfoot	Congenital Clubfoot	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital kyphoscoliosis	Congenital kyphoscoliosis	BEFREE	28777491		★☆☆☆☆ Found in Text Mining only
Congenital kyphoscoliosis	Congenital kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital myopathy (disorder)	Congenital myopathy	BEFREE	29950399, 30168660		★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysmorphic features	Dysmorphic Features	BEFREE	30168660		★☆☆☆☆ Found in Text Mining only
Gastroesophageal reflux disease	Gastroesophageal Reflux Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	28777491	Associate	★☆☆☆☆ Found in Text Mining only
Hypokalemic periodic paralysis	Hypokalemic Periodic Paralysis	BEFREE	29386226		★☆☆☆☆ Found in Text Mining only
Liver neoplasms	Liver neoplasms	CTD_human_DG	28108177		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant Hyperthermia	Malignant hyperthermia	Pubtator	28777491, 40262809	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	CTD_human_DG	28108177		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mobius Syndrome	Mobius Syndrome	BEFREE	28777491		★☆☆☆☆ Found in Text Mining only
Mobius Syndrome	Mobius syndrome	Pubtator	28777491	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	BEFREE	30275178		★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	BEFREE	28112192, 29363593, 30071129		★☆☆☆☆ Found in Text Mining only
Myopathy, congenital nonprogressive with Moebius and Robin sequences	Carey Fineman Ziter syndrome	BEFREE	28777491		★☆☆☆☆ Found in Text Mining only
Myotonia Congenita	Myotonia congenita	Pubtator	29950399, 35205385, 40262809	Associate	★☆☆☆☆ Found in Text Mining only
Native American myopathy	Native American Myopathy	BEFREE	23736855, 28003463, 28112192, 28411587, 28777491, 29078335		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Native American myopathy	Native American Myopathy	UNIPROT_DG	23736855, 28777491, 29078335		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Native American myopathy	Native American Myopathy	CLINVAR_DG	23736855, 28411587, 28777491		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Native American myopathy	Native American Myopathy	GENOMICS_ENGLAND_DG	23736855, 28003463		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Native American myopathy	Native American Myopathy	ORPHANET_DG	23736855		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Native American myopathy	Native American Myopathy	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Native American myopathy	Native american myopathy	Pubtator	28777491, 35205385, 40262809	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Native American myopathy	Native American Myopathy	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neuromuscular Diseases	Neuromuscular disease	Pubtator	40262809	Associate	★☆☆☆☆ Found in Text Mining only
Progressive congenital scoliosis	Congenital Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	BEFREE	28777491		★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Scoliosis	Scoliosis	Pubtator	28777491	Associate	★☆☆☆☆ Found in Text Mining only
Submucous cleft soft palate	Submucous cleft of soft and hard palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Talipes	Talipes	HPO_DG			★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	37042849	Associate	★☆☆☆☆ Found in Text Mining only