FIBCD1
protein-codingfibrinogen C domain containing 1, the group of Fibrinogen C domain containing
Gene summary
FIBCD1 is a conserved type II transmembrane endocytic receptor that binds chitin and is located primarily in the intestinal brush border (Schlosser et al., 2009 [PubMed 19710473]).[supplied by OMIM, Apr 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~36.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0100038
Submitter: LiferaOmics
Genetic evidence – Published: PMID: 35916241 – Reports 2 independent families with biallelic FIBCD1 missense variants associated with a neurodevelopmental disorder phenotype. Case-level: case 1=(1 compound heterozygous proband with two missense variants confirmed in trans; AR model; each non-LOF variant scored independently, non-LOF start 1; no consanguinity deduction stated) = 0.2; case 2= (1 homozygous missense proband due to paternal uniparental disomy; non-LOF; homozygous scored once; no consanguinity deduction stated) = 1.0; segregation (parental heterozygous transmission confirmed in compound heterozygous family; conservative) = 0.5; case-control = 0 Published genetic evidence total = case-level (0.2 + 1.0 = 1.2) + segregation (0.5) = 1.7/12 Genetic evidence – our cases: Family 1 – 1 proband; Case-level (biallelic predicted null in AR model; homozygous scored once; AR predicted null default 1.5; −0.5 consanguinity deduction applied) = 1.0; segregation = 0 (parental heterozygosity not explicitly confirmed here); case-control = 0 Our cases total = case-level (1.0) + segregation (0) = 1.0/12 Total genetic evidence (published + our cases) = 1.7 + 1.0 = 2.7/12 Experimental evidence – Published: PMID: 35916241 – Demonstrates that FIBCD1 encodes a brain-expressed endocytic receptor for chondroitin sulfate glycosaminoglycans with relevance to extracellular matrix regulation and synaptic plasticity (biochemical function/biological plausibility) = 1.0. Functional alteration in engineered systems shows patient missense variants impair ligand binding and downstream cellular responses consistent with loss-of-function mechanism = 2.0. Model systems (Drosophila knockdown and mouse knockout) demonstrate synaptic abnormalities, impaired hippocampal-dependent learning, and altered synaptic plasticity consistent with the patient neurodevelopmental phenotype, with partial rescue of synaptic plasticity via ECM modulation = 2.0 Experimental evidence total = 5.0/6 Overall score = 7.7
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FIBCD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032843.5. 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 | 1 | 2 | 3 | |||
| missense | 121 | 5 | 126 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 122 | 7 | 0 | 129 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_116232.3 | 7 | MANE Select | |
| Ensembl | ENSP00000361413.4 | 7 | MANE Select | |
| RefSeq | NP_001138578.1 | 7 | Standard | |
| Ensembl | ENSP00000361412.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Molecular Function
- protein binding
- chitin binding
- metal ion binding
Cellular Component
- membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000372338
- Coding exons
- 7
- Length
- 36849
- Individuals with no LoFs
- 125533
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 125
- Defined
- 125659
- p
- 0.000501
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.382 | 294 | 313 | 0.939 | 0.0000235 | 2924 |
| Missense (PolyPhen) | 99 | 110.42 | 0.8966 | 994 | ||
| Synonymous | -0.377 | 154 | 148 | 1.04 | 0.0000123 | 969 |
| Loss of Function | -0.393 | 20 | 18.2 | 1.10 | 0.00000103 | 180 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00053 | 0.00049 | rare |
| Latino/Admixed American | 0.0012 | 0.0012 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00016 | rare |
| Finnish | 0.00029 | 0.00028 | rare |
| European (Non-Finnish) | 0.00040 | 0.00038 | rare |
| South Asian | 0.00087 | 0.00078 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acetyl group-binding receptor which shows a high- affinity and calcium-dependent binding to acetylated structures such as chitin, some N-acetylated carbohydrates, and amino acids, but not to their non-acetylated counterparts. Can facilitate the endocytosis of acetylated components. {ECO:0000269|PubMed:19710473, ECO:0000269|PubMed:19892701}.;
Recessive Scores
- pRec
- 0.107
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |