ANKRD27
protein-codingankyrin repeat domain 27, the group of Ankyrin repeat domain containing|VPS9 domain containing|Small nucleolar RNA protein coding host genes
Gene summary
Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in endocytic recycling and negative regulation of SNARE complex assembly. Acts upstream of or within early endosome to late endosome transport. Located in endosome; lysosome; and plasma membrane. Implicated in eosinophilic esophagitis. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~79.6 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 ANKRD27 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032139.3. 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 | 2 | 2 | ||||
| missense | 165 | 10 | 175 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 14 | 14 | ||||
| Total | 0 | 0 | 179 | 12 | 0 | 191 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115515.2 | 28 | MANE Select | |
| Ensembl | ENSP00000304292.3 | 28 | MANE Select | |
| Ensembl | ENSP00000467447.1 | 2 | Standard | |
| Ensembl | ENSP00000476897.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Rab regulation of trafficking
- RAB GEFs exchange GTP for GDP on RABs
Biological Process
- protein transport
- negative regulation of SNARE complex assembly
- endosome to melanosome transport
- positive regulation of GTPase activity
- early endosome to late endosome transport
Molecular Function
- SNARE binding
- guanyl-nucleotide exchange factor activity
- GTPase activator activity
- protein binding
- Rab guanyl-nucleotide exchange factor activity
Cellular Component
- lysosome
- early endosome
- late endosome
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000306065
- Coding exons
- 28
- Length
- 79591
- Individuals with no LoFs
- 125555
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 192
- Defined
- 125748
- p
- 0.000768
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.271 | 602 | 584 | 1.03 | 0.0000340 | 6847 |
| Missense (PolyPhen) | 60 | 60.327 | 0.99457 | 628 | ||
| Synonymous | -0.588 | 257 | 245 | 1.05 | 0.0000166 | 2015 |
| Loss of Function | 0.885 | 51 | 58.3 | 0.875 | 0.00000288 | 699 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00050 | 0.00043 | rare |
| Latino/Admixed American | 0.00089 | 0.00087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00060 | 0.00060 | rare |
| Finnish | 0.00084 | 0.00083 | rare |
| European (Non-Finnish) | 0.00075 | 0.00072 | rare |
| South Asian | 0.0014 | 0.0013 | notable |
| Other | 0.00085 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be a guanine exchange factor (GEF) for Rab21, Rab32 and Rab38 and regulate endosome dynamics (PubMed:16525121, PubMed:18477474). May regulate the participation of VAMP7 in membrane fusion events; in vitro inhibits VAMP7-mediated SNARE complex formation by trapping VAMP7 in a closed, fusogenically inactive conformation (PubMed:23104059). Involved in peripheral melanosomal distribution of TYRP1 in melanocytes; the function, which probably is implicating vesicle-trafficking, includes cooperation with Rab32, Rab38 and VAMP7 (By similarity). Involved in the regulation of neurite growth; the function seems to require its GEF activity, probably towards Rab21, and VAMP7 but not Rab32/38 (By similarity). Proposed to be involved in Golgi sorting of VAMP7 and transport of VAMP7 vesicles to the cell surface; the function seems to implicate kinesin heavy chain isoform 5 proteins, GOLGA4, RAB21 and MACF1 (PubMed:22705394). Required for the colocalization of VAMP7 and Rab21, probably on TGN sites (PubMed:19745841). Involved in GLUT1 endosome-to-plasma membrane trafficking; the function is dependent of association with VPS29 (PubMed:24856514). Regulates the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes (By similarity). {ECO:0000250|UniProtKB:Q3UMR0, ECO:0000269|PubMed:23104059, ECO:0000269|PubMed:24856514, ECO:0000305|PubMed:16525121, ECO:0000305|PubMed:18477474, ECO:0000305|PubMed:22705394}.;
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- LoFtool
- 0.956
- RVIS EVS
- -1.56
- RVIS percentile EVS
- 3.21
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.347
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |