SARAF
protein-codingstore-operated calcium entry associated regulatory factor
Gene summary
Involved in regulation of store-operated calcium entry. Located in endoplasmic reticulum membrane and endoplasmic reticulum-plasma membrane contact site. [provided by Alliance of Genome Resources, Jul 2025]
- TMEM66
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.2 kbGenCC 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 SARAF variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016127.6. 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 | 0 | |||||
| missense | 46 | 1 | 47 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 46 | 1 | 0 | 47 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057211.4 | 6 | MANE Select | |
| Ensembl | ENSP00000256255.6 | 6 | MANE Select | |
| RefSeq | NP_001271168.1 | 4 | Standard | |
| Ensembl | ENSP00000431005.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- calcium ion transport
- regulation of store-operated calcium entry
Molecular Function
- protein binding
Cellular Component
- endoplasmic reticulum
- integral component of endoplasmic reticulum membrane
- endoplasmic reticulum-plasma membrane contact site
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000256255
- Coding exons
- 6
- Length
- 20196
- Individuals with no LoFs
- 124857
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 891
- Defined
- 125748
- p
- 0.00355
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.489 | 169 | 188 | 0.900 | 0.00000995 | 2142 |
| Missense (PolyPhen) | 73 | 81.748 | 0.89299 | 934 | ||
| Synonymous | 0.472 | 72 | 77.3 | 0.932 | 0.00000456 | 684 |
| Loss of Function | 2.06 | 7 | 15.8 | 0.442 | 6.66e-7 | 209 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00065 | 0.00062 | rare |
| Latino/Admixed American | 0.00097 | 0.00078 | rare |
| Ashkenazi Jewish | 0.0026 | 0.0022 | notable |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.017 | 0.014 | notable |
| European (Non-Finnish) | 0.0039 | 0.0036 | notable |
| South Asian | 0.0037 | 0.0031 | notable |
| Other | 0.0052 | 0.0044 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Negative regulator of store-operated Ca(2+) entry (SOCE) involved in protecting cells from Ca(2+) overfilling. In response to cytosolic Ca(2+) elevation after endoplasmic reticulum Ca(2+) refilling, promotes a slow inactivation of STIM (STIM1 or STIM2)- dependent SOCE activity: possibly act by facilitating the deoligomerization of STIM to efficiently turn off ORAI when the endoplasmic reticulum lumen is filled with the appropriate Ca(2+) levels, and thus preventing the overload of the cell with excessive Ca(2+) ions. {ECO:0000269|PubMed:22464749}.;
Recessive Scores
- pRec
- 0.123
Intolerance Scores
- RVIS EVS
- -0.4
- RVIS percentile EVS
- 26.53
Essentials
- Essential (gene trap)
- N