ERC1
protein-codingELKS/RAB6-interacting/CAST family member 1
Gene summary
The protein encoded by this gene is a member of a family of RIM-binding proteins. RIMs are active zone proteins that regulate neurotransmitter release. This gene has been found fused to the receptor-type tyrosine kinase gene RET by gene rearrangement due to the translocation t(10;12)(q11;p13) in thyroid papillary carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
- RAB6IP2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~505.4 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 ERC1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_178040.4. 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 | 2 | 6 | |||
| missense | 138 | 1 | 3 | 142 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 1 | 142 | 5 | 5 | 153 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_829884.1 | 18 | MANE Select | |
| Ensembl | ENSP00000354158.3 | 18 | MANE Select | |
| RefSeq | NP_001288177.1 | 18 | Standard | |
| RefSeq | NP_829883.1 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- NF-kappa B signaling pathway - Homo sapiens (human)
- Integrated Lung Cancer Pathway
- Canonical NF-kappaB pathway
- IL1-mediated signaling events
Biological Process
- regulation of transcription, DNA-templated
- I-kappaB phosphorylation
- multicellular organism development
- protein transport
- retrograde transport, endosome to Golgi
Molecular Function
- protein binding
- Rab GTPase binding
- PDZ domain binding
- leucine zipper domain binding
- cadherin binding
Cellular Component
- Golgi membrane
- cytoplasm
- IkappaB kinase complex
- presynaptic membrane
- synapse
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000397203
- Coding exons
- 18
- Length
- 505425
- Individuals with no LoFs
- 125692
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 56
- Defined
- 125748
- p
- 0.000223
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.45 | 510 | 611 | 0.834 | 0.0000344 | 7407 |
| Missense (PolyPhen) | 230 | 294.15 | 0.78192 | 3537 | ||
| Synonymous | -1.34 | 246 | 221 | 1.11 | 0.0000117 | 2048 |
| Loss of Function | 4.43 | 23 | 60.0 | 0.383 | 0.00000353 | 691 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.00071 | 0.00071 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00027 | 0.00026 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulatory subunit of the IKK complex. Probably recruits IkappaBalpha/NFKBIA to the complex. May be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. May be involved in vesicle trafficking at the CAZ. May be involved in Rab-6 regulated endosomes to Golgi transport. {ECO:0000269|PubMed:15218148}.;
Recessive Scores
- pRec
- 0.233
Intolerance Scores
- LoFtool
- 0.323
- RVIS EVS
- -0.88
- RVIS percentile EVS
- 10.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.610
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |