AFDN
protein-codingafadin, adherens junction formation factor, the group of PDZ domain containing
Gene summary
This gene encodes a multi-domain protein involved in signaling and organization of cell junctions during embryogenesis. It has also been identified as the fusion partner of acute lymphoblastic leukemia (ALL-1) gene, involved in acute myeloid leukemias with t(6;11)(q27;q23) translocation. Alternatively spliced transcript variants encoding different isoforms have been described for this gene, however, not all have been fully characterized.[provided by RefSeq, May 2011]
- MLLT4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~145.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0016044
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to AFDN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001386888.1. 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 | 5 | 3 | 1 | 9 | ||
| missense | 25 | 25 | ||||
| nonsense | 5 | 5 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 11 | 11 | ||||
| Total | 0 | 0 | 47 | 3 | 1 | 51 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001373817.1 | 34 | MANE Select | |
| Ensembl | ENSP00000507324.1 | 34 | MANE Select | |
| RefSeq | NP_001035089.1 | 30 | Standard | |
| RefSeq | NP_001193937.1 | 32 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Adherens junction - Homo sapiens (human)
- Tight junction - Homo sapiens (human)
- cAMP signaling pathway - Homo sapiens (human)
- Rap1 signaling pathway - Homo sapiens (human)
- Ras signaling pathway - Homo sapiens (human)
Biological Process
- cell adhesion
- signal transduction
- cell-cell signaling
- negative regulation of cell migration
- regulation of protein localization
Molecular Function
- protein binding
- protein C-terminus binding
- Ras GTPase binding
- cadherin binding
- cell adhesion molecule binding
Cellular Component
- nucleoplasm
- cytosol
- plasma membrane
- cell-cell junction
- cell-cell adherens junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000392108
- Coding exons
- 30
- Length
- 145102
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 125748
- p
- 0.0000835
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.21 | 771 | 964 | 0.800 | 0.0000576 | 10844 |
| Missense (PolyPhen) | 299 | 452.81 | 0.66032 | 5140 | ||
| Synonymous | -0.571 | 367 | 353 | 1.04 | 0.0000211 | 3148 |
| Loss of Function | 7.47 | 11 | 85.5 | 0.129 | 0.00000490 | 967 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000085 | 0.000079 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton.;
- Disease
- DISEASE: Note=A chromosomal aberration involving AFDN is associated with acute leukemias. Translocation t(6;11)(q27;q23) with KMT2A/MLL1. The result is a rogue activator protein.;
Recessive Scores
- pRec
- 0.378
Intolerance Scores
- RVIS EVS
- -2.36
- RVIS percentile EVS
- 1.14
Essentials
- Essential (gene trap)
- N