STEAP4
protein-codingSTEAP4 metalloreductase, the group of STEAP family
Gene summary
The protein encoded by this gene belongs to the STEAP (six transmembrane epithelial antigen of prostate) family, and resides in the golgi apparatus. It functions as a metalloreductase that has the ability to reduce both Fe(3+) to Fe(2+) and Cu(2+) to Cu(1+), using NAD(+) as acceptor. Studies in mice and human suggest that this gene maybe involved in adipocyte development and metabolism, and may contribute to the normal biology of the prostate cell, as well as prostate cancer progression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2011]
- TNFAIP9
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~36.0 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 STEAP4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024636.4. 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 | 1 | 3 | |||
| missense | 35 | 2 | 2 | 39 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 37 | 3 | 2 | 42 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_078912.2 | 4 | MANE Select | |
| Ensembl | ENSP00000369419.4 | 4 | MANE Select | |
| RefSeq | NP_001192244.1 | 4 | Standard | |
| RefSeq | NP_001192245.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vitamin D Receptor Pathway
- Copper homeostasis
Biological Process
- copper ion import
- fat cell differentiation
- iron ion homeostasis
- oxidation-reduction process
- iron ion import across cell outer membrane
Molecular Function
- cupric reductase activity
- metal ion binding
- ferric-chelate reductase (NADPH) activity
Cellular Component
- Golgi membrane
- endosome
- Golgi apparatus
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000380079
- Coding exons
- 4
- Length
- 30463
- Individuals with no LoFs
- 124512
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 273
- Defined
- 124787
- p
- 0.00110
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.843 | 208 | 245 | 0.848 | 0.0000123 | 2948 |
| Missense (PolyPhen) | 64 | 84.686 | 0.75573 | 1022 | ||
| Synonymous | 0.266 | 86 | 89.2 | 0.964 | 0.00000431 | 948 |
| Loss of Function | 1.45 | 14 | 21.2 | 0.659 | 0.00000145 | 221 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.012 | 0.012 | notable |
| Latino/Admixed American | 0.0010 | 0.00099 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00028 | 0.00028 | rare |
| South Asian | 0.00043 | 0.00042 | rare |
| Other | 0.00066 | 0.00066 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Metalloreductase that has the ability to reduce both Fe(3+) to Fe(2+) and Cu(2+) to Cu(1+) (By similarity). Uses NADP(+) as acceptor (By similarity). Plays a role in systemic metabolic homeostasis, integrating inflammatory and metabolic responses (By similarity). Associated with obesity and insulin- resistance (PubMed:18430367, PubMed:18381574). Involved in inflammatory arthritis, through the regulation of inflammatory cytokines (PubMed:19660107). Inhibits anchorage-independent cell proliferation (PubMed:19787193). {ECO:0000250, ECO:0000269|PubMed:18381574, ECO:0000269|PubMed:18430367, ECO:0000269|PubMed:19660107, ECO:0000269|PubMed:19787193}.;
Recessive Scores
- pRec
- 0.0817
Intolerance Scores
- LoFtool
- 0.524
- RVIS EVS
- 0.82
- RVIS percentile EVS
- 87.95
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.375
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |