C21orf91
protein-codingchromosome 21 open reading frame 91
Gene summary
Predicted to be involved in cerebral cortex neuron differentiation and positive regulation of dendritic spine development. [provided by Alliance of Genome Resources, Jul 2025]
- C21orf38
- C21orf14
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~30.4 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 C21orf91 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001100420.2. 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 | ||||
| missense | 1 | 1 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 2 | 1 | 0 | 3 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001093890.1 | 4 | MANE Select | |
| Ensembl | ENSP00000284881.4 | 4 | MANE Select | |
| RefSeq | NP_001093891.1 | 3 | Standard | |
| RefSeq | NP_059143.3 | 4 | Standard |
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000284881
- Coding exons
- 4
- Length
- 30420
- Individuals with no LoFs
- 124755
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 38
- Defined
- 124793
- p
- 0.000152
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.354 | 138 | 150 | 0.919 | 0.00000714 | 1982 |
| Missense (PolyPhen) | 48 | 58.186 | 0.82495 | 788 | ||
| Synonymous | -0.512 | 60 | 55.2 | 1.09 | 0.00000271 | 526 |
| Loss of Function | 1.68 | 7 | 13.7 | 0.510 | 6.49e-7 | 166 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00095 | 0.00089 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in cortical progenitor cell proliferation and differentiation. Promotes dendritic spine development of post- migratory cortical projection neurons by modulating the beta- catenin signaling pathway. {ECO:0000250|UniProtKB:Q9D7G4}.;
Recessive Scores
- pRec
- 0.0978
Intolerance Scores
- LoFtool
- 0.886
- RVIS EVS
- 0.79
- RVIS percentile EVS
- 87.4
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |