IGBP1
protein-codingimmunoglobulin binding protein 1, the group of Protein phosphatase 2 modulatory subunits
Gene summary
The proliferation and differentiation of B cells is dependent upon a B-cell antigen receptor (BCR) complex. Binding of antigens to specific B-cell receptors results in a tyrosine phosphorylation reaction through the BCR complex and leads to multiple signal transduction pathways. [provided by RefSeq, Jul 2008]
- IBP1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~32.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0010333
Submitter: Ambry Genetics
Inheritance Pattern: XL
Disease ID:MONDO:0010333
Submitter: G2P
Inheritance Pattern: XL
Disease ID:MONDO:0010333
Submitter: Orphanet
Inheritance Pattern: XL
Disease ID:MONDO:0010333
Submitter: PanelApp Australia
Inheritance Pattern: XL
Disease ID:MONDO:0010333
Submitter: ClinGen
IGBP1 was first reported in relation to X-linked corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome in 2003 (Graham et al., PMID: 14556245). Two brothers with intellectual disability, macrocephaly, short stature, scoliosis, retrognathia, coloboma, and agenesis of corpus callosum were found to share a maternally inherited 5’ UTR variant in IGBP1 (c.-57_-55delTATinsAA) (PMID: 14556245). Analysis of IGBP1 expression in skin fibroblasts of an affected individual showed normal localization, with 20% increase in protein levels. Because there was no evidence of a deleterious effect of the variant and investigation into additional potential etiologies was limited, this variant was not scored. In 2017, a large exome sequencing study in individuals with developmental disorders reported a de novo missense variant in IGBP1, without phenotype information (DDD Study, PMID: 28135719). This variant is absent from gnomAD v2.1.1, but since there is no functional evidence of pathogenicity, it was not scored. In terms of experimental evidence, the IGBP1 protein binds to MID1 (PMID: 11371618), which is associated with syndromic X-linked intellectual disability (Opitz G/BBB syndrome). In the context of extremely limited genetic evidence, we opted not to score this experimental evidence. In summary, the evidence supporting the relationship between IGBP1 and X-linked corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome is disputed. More evidence is needed to either support or entirely refute the role IGBP1 plays in this disease. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on 2/2/2021 (SOP Version 8).
Inheritance Pattern: Unknown
Disease ID:MONDO:0010333
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic
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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IGBP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001551.3. 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 | 4 | 5 | 1 | 10 | ||
| missense | 53 | 3 | 56 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 66 | 8 | 1 | 75 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001542.1 | 6 | MANE Select | |
| Ensembl | ENSP00000348784.4 | 6 | MANE Select | |
| RefSeq | NP_001357121.1 | 6 | Standard | |
| RefSeq | NP_001357122.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Autophagy - animal - Homo sapiens (human)
- Autophagy - other - Homo sapiens (human)
Biological Process
- negative regulation of transcription by RNA polymerase II
- signal transduction
- negative regulation of stress-activated MAPK cascade
- response to tumor necrosis factor
- B cell activation
Molecular Function
- protein binding
- protein phosphatase regulator activity
- protein phosphatase 2A binding
Cellular Component
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000342206
- Coding exons
- 6
- Length
- 32876
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.30 | 90 | 132 | 0.681 | 0.00000997 | 2232 |
| Missense (PolyPhen) | 8 | 25.628 | 0.31216 | 514 | ||
| Synonymous | -0.872 | 54 | 46.4 | 1.16 | 0.00000332 | 620 |
| Loss of Function | 3.26 | 0 | 12.4 | 0.00 | 8.85e-7 | 213 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Associated to surface IgM-receptor; may be involved in signal transduction. Involved in regulation of the catalytic activity of the phosphatases PP2A, PP4 and PP6 by protecting their partially folded catalytic subunits from degradative polyubiquitination until they associate with regulatory subunits. {ECO:0000269|PubMed:19818709, ECO:0000269|PubMed:23591866}.;
- Disease
- DISEASE: Mental retardation, X-linked, syndromic, 28 (MRXS28) [MIM:300472]: A mental retardation syndrome characterized by agenesis of the corpus callosum, coloboma of the iris and optic nerve, severe retrognathia, and intellectual deficit. Mental retardation is defined by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:14556245}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- RVIS EVS
- 0.26
- RVIS percentile EVS
- 70.26
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.310
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |