STAC

protein-coding

SH3 and cysteine rich domain

Gene summary

Predicted to enable transmembrane transporter binding activity. Predicted to be involved in positive regulation of protein localization to plasma membrane; positive regulation of voltage-gated calcium channel activity; and skeletal muscle contraction. Predicted to act upstream of or within cellular response to heat; muscle contraction; and regulation of voltage-gated calcium channel activity. Predicted to be located in cytoplasmic side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2025]

MANE transcript

NM_003149.3

Inheritance

—

ClinVar variants

U:53B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr3:36,380,503-36,548,007

External References & Databases

Ensembl (ENSG00000144681)

Transcript & Mutation Effects

hg38 • Region Span ~167.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to STAC variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 48

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003149.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar			2
missense			49 clinvar	1 clinvar	2 clinvar	52
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	53	1	2	56

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003149.3	RefSeq	NP_003140.1	11	MANE Select
ENST00000273183.8	Ensembl	ENSP00000273183.3	11	MANE Select
NM_001292049.2	RefSeq	NP_001278978.1	9	Standard
ENST00000427486.5	Ensembl	ENSP00000397521.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

muscle contraction
signal transduction
cellular response to heat
intracellular signal transduction
positive regulation of voltage-gated calcium channel activity

Molecular Function

protein binding
ion channel binding
metal ion binding

Cellular Component

cytosol
T-tubule
extrinsic component of cytoplasmic side of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000273183
Coding exons: 11
Length: 167664
Individuals with no LoFs: 125662
Homozygous LoFs: 1
Heterozygous LoFs: 85
Defined: 125748
p: 0.000342

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.304	209	222	0.943	0.0000117	2657
Missense (PolyPhen)		78	86.393	0.90285		1043
Synonymous	-1.51	98	80.8	1.21	0.00000424	734
Loss of Function	1.52	14	21.6	0.648	0.00000110	255

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00039	0.00038	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.0018	0.0018	notable
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.000099	0.000098	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Promotes expression of the ion channel CACNA1H at the cell membrane, and thereby contributes to the regulation of channel activity. Plays a minor and redundant role in promoting the expression of calcium channel CACNA1S at the cell membrane, and thereby contributes to increased channel activity. Slows down the inactivation rate of the calcium channel CACNA1C. {ECO:0000250|UniProtKB:P97306}.;

Recessive Scores

pRec: 0.0931

Intolerance Scores

RVIS EVS: -0.18
RVIS percentile EVS: 40.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.197

Gene Damage Prediction

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