ARK2C
protein-codingarkadia (RNF111) C-terminal like ring finger ubiquitin ligase 2C, the group of Ring finger proteins
Gene summary
Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in motor neuron axon guidance and positive regulation of BMP signaling pathway. Predicted to act upstream of or within several processes, including forelimb morphogenesis; nervous system development; and protein polyubiquitination. Predicted to be part of protein-containing complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]
- RNF165
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~136.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ARK2C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152470.3. 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 | 1 | 1 | 2 | |||
| missense | 22 | 22 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 24 | 1 | 0 | 25 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689683.2 | 8 | MANE Select | |
| Ensembl | ENSP00000269439.6 | 8 | MANE Select | |
| RefSeq | NP_001243687.1 | 5 | Standard | |
| Ensembl | ENSP00000444285.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein polyubiquitination
- motor neuron axon guidance
- multicellular organism aging
- protein catabolic process
- positive regulation of BMP signaling pathway
Molecular Function
- protein binding
- zinc ion binding
- ubiquitin protein ligase activity
Cellular Component
- nucleus
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000269439
- Coding exons
- 8
- Length
- 136332
- Individuals with no LoFs
- 125740
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125748
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.94 | 134 | 214 | 0.627 | 0.0000129 | 2247 |
| Missense (PolyPhen) | 36 | 71.346 | 0.50459 | 780 | ||
| Synonymous | -0.131 | 91 | 89.4 | 1.02 | 0.00000566 | 687 |
| Loss of Function | 3.71 | 2 | 19.8 | 0.101 | 0.00000108 | 190 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| 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) | 0.000062 | 0.000062 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase that acts as a regulator of motor axon elongation. Required for efficient motor axon extension in the dorsal forelimb by enhancing the transcriptional responses of the SMAD1/SMAD5/SMAD8 effectors, which are activated downstream of BMP. Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD6, SMAD7, SKI and SNON isoform of SKIL. {ECO:0000250|UniProtKB:E9QAU8}.;
Recessive Scores
- pRec
- 0.0880
Intolerance Scores
- LoFtool
- 0.0847
- RVIS EVS
- -0.36
- RVIS percentile EVS
- 28.93
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |