NFASC
protein-codingneurofascin, the group of Fibronectin type III domain containing|I-set domain containing|Ig-like cell adhesion molecule family
Gene summary
This gene encodes an L1 family immunoglobulin cell adhesion molecule with multiple IGcam and fibronectin domains. The protein functions in neurite outgrowth, neurite fasciculation, and organization of the axon initial segment (AIS) and nodes of Ranvier on axons during early development. Both the AIS and nodes of Ranvier contain high densities of voltage-gated Na+ (Nav) channels which are clustered by interactions with cytoskeletal and scaffolding proteins including this protein, gliomedin, ankyrin 3 (ankyrin-G), and betaIV spectrin. This protein links the AIS extracellular matrix to the intracellular cytoskeleton. This gene undergoes extensive alternative splicing, and the full-length nature of some variants has not been determined.[provided by RefSeq, May 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~194.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0032698
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0032698
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0032698
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0032698
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Neurologic
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 NFASC variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001005388.3. 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 | 38 | 8 | 50 | ||
| missense | 5 | 201 | 35 | 3 | 244 | |
| nonsense | 2 | 2 | 4 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 6 | 2 | 213 | 73 | 11 | 305 |
Highest pathogenic variant AF is 0.000029750652
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001005388.2 | 28 | MANE Select | |
| Ensembl | ENSP00000344786.6 | 28 | MANE Select | |
| RefSeq | NP_001005389.2 | 14 | Standard | |
| RefSeq | NP_001153803.1 | 27 | MANE Plus Clinical |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- Developmental Biology
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- protein localization to paranode region of axon
- axon guidance
- peripheral nervous system development
- transmission of nerve impulse
- paranodal junction assembly
Molecular Function
- protein binding
- protein domain specific binding
- protein binding involved in heterotypic cell-cell adhesion
Cellular Component
- plasma membrane
- focal adhesion
- integral component of membrane
- dendrite
- paranodal junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000339876
- Coding exons
- 28
- Length
- 194172
- Individuals with no LoFs
- 125734
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 14
- Defined
- 125748
- p
- 0.0000557
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.59 | 588 | 793 | 0.741 | 0.0000518 | 8068 |
| Missense (PolyPhen) | 194 | 331.88 | 0.58455 | 3432 | ||
| Synonymous | 0.216 | 328 | 333 | 0.985 | 0.0000246 | 2479 |
| Loss of Function | 6.69 | 8 | 67.1 | 0.119 | 0.00000380 | 691 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00024 | 0.00020 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.000034 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cell adhesion, ankyrin-binding protein which may be involved in neurite extension, axonal guidance, synaptogenesis, myelination and neuron-glial cell interactions. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.197
Intolerance Scores
- LoFtool
- 0.529
- RVIS EVS
- -1.8
- RVIS percentile EVS
- 2.21
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.285
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |