USP6NL
protein-codingUSP6 N-terminal like
Gene summary
Enables GTPase activator activity and small GTPase binding activity. Involved in several processes, including plasma membrane to endosome transport; positive regulation of GTPase activity; and retrograde transport, plasma membrane to Golgi. Located in cytoplasmic vesicle and plasma membrane. Is active in cytosol. [provided by Alliance of Genome Resources, Jun 2026]
- USP6NL-IT1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~151.2 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 USP6NL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014688.5. 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 | 2 | 2 | ||||
| missense | 147 | 6 | 153 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 153 | 6 | 0 | 159 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055503.1 | 14 | MANE Select | |
| Ensembl | ENSP00000476462.1 | 14 | MANE Select | |
| RefSeq | NP_001073960.1 | 14 | Standard | |
| RefSeq | NP_001378888.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- EGF-EGFR Signaling Pathway
- Vesicle-mediated transport
- Membrane Trafficking
- EGFR1
- ErbB1 downstream signaling
Biological Process
- intracellular protein transport
- Golgi organization
- virion assembly
- retrograde transport, plasma membrane to Golgi
- positive regulation of GTPase activity
Molecular Function
- GTPase activator activity
- Rab GTPase binding
Cellular Component
- cytosol
- plasma membrane
- cytoplasmic vesicle
- trans-Golgi network membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000277575
- Coding exons
- 14
- Length
- 157809
- Individuals with no LoFs
- 124583
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 59
- Defined
- 124642
- p
- 0.000237
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.146 | 468 | 459 | 1.02 | 0.0000272 | 5484 |
| Missense (PolyPhen) | 93 | 123.42 | 0.75351 | 1492 | ||
| Synonymous | -0.876 | 202 | 187 | 1.08 | 0.0000127 | 1637 |
| Loss of Function | 4.43 | 10 | 40.3 | 0.248 | 0.00000246 | 494 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00039 | 0.00039 | rare |
| Latino/Admixed American | 0.00047 | 0.00046 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00018 | 0.00018 | rare |
| South Asian | 0.00046 | 0.00046 | rare |
| Other | 0.00018 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a GTPase-activating protein for RAB5A and RAB43. Involved in receptor trafficking. In complex with EPS8 inhibits internalization of EGFR. Involved in retrograde transport from the endocytic pathway to the Golgi apparatus. Involved in the transport of Shiga toxin from early and recycling endosomes to the trans-Golgi network. Required for structural integrity of the Golgi complex. {ECO:0000269|PubMed:11099046, ECO:0000269|PubMed:17562788, ECO:0000269|PubMed:17684057}.;
Recessive Scores
- pRec
- 0.152
Intolerance Scores
- LoFtool
- 0.878
- RVIS EVS
- -0.75
- RVIS percentile EVS
- 13.67
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.752
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |