IFITM5
protein-codinginterferon induced transmembrane protein 5, the group of Interferon induced transmembrane proteins
Gene summary
This gene encodes a membrane protein thought to play a role in bone mineralization. This gene is located on chromosome 11 in a cluster of related genes which are induced by interferon, however, this gene has not been shown to be interferon inducible. A similar gene, located in a gene cluster on mouse chromosome 7, is a member of the interferon-inducible fragilis gene family. The mouse gene encodes a transmembrane protein described as participating in germ cell competence. A mutation in the 5' UTR of this gene has been associated with osteogenesis imperfecta type V (PMID: 22863190, 22863195). [provided by RefSeq, Aug 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0012591
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0012591
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0012591
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0012591
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: Pamidronate treatment has been described as beneficial in terms of reducing fracture risk, but the advantage of early (genetic) diagnosis is unclear
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IFITM5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001025295.3. 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 | 28 | 4 | 32 | |||
| missense | 1 | 1 | 69 | 32 | 5 | 108 |
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 1 | 1 | 6 | ||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 1 | 1 | 74 | 63 | 10 | 149 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001020466.1 | 2 | MANE Select | |
| Ensembl | ENSP00000372059.2 | 2 | MANE Select | |
| Ensembl | ENSP00000811331.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- in utero embryonic development
- bone mineralization
- regulation of bone mineralization
- bone morphogenesis
Cellular Component
- plasma membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000382614
- Coding exons
- 2
- Length
- 1327
- Individuals with no LoFs
- 125318
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 68
- Defined
- 125386
- p
- 0.000271
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.668 | 94 | 77.5 | 1.21 | 0.00000533 | 800 |
| Missense (PolyPhen) | 35 | 25.96 | 1.3482 | 296 | ||
| Synonymous | -0.0763 | 38 | 37.4 | 1.02 | 0.00000263 | 288 |
| Loss of Function | -1.32 | 7 | 4.11 | 1.70 | 3.12e-7 | 38 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.0011 | 0.0011 | notable |
| East Asian | 0.00071 | 0.00071 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00024 | 0.00024 | rare |
| South Asian | 0.00048 | 0.00046 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for normal bone mineralization. {ECO:0000269|PubMed:24519609}.;
- Disease
- DISEASE: Osteogenesis imperfecta 5 (OI5) [MIM:610967]: An autosomal dominant form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI5 patients manifest moderate to severe bone fragility, calcification of the forearm interosseous membrane, radial head dislocation, a subphyseal metaphyseal radiodense line, and hyperplastic callus formation. {ECO:0000269|PubMed:22863190, ECO:0000269|PubMed:24519609}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.408
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 64.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.146
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |