ARHGAP44
protein-codingRho GTPase activating protein 44, the group of AH/BAR family Rho GTPase activating proteins|N-BAR domain containing
Gene summary
Enables phospholipid binding activity. Predicted to be involved in negative regulation of Rac protein signal transduction; regulation of actin cytoskeleton organization; and regulation of plasma membrane bounded cell projection organization. Located in leading edge membrane. Implicated in acquired immunodeficiency syndrome and skin melanoma. Biomarker of hepatocellular carcinoma and lung carcinoma. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~202.1 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 ARHGAP44 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014859.6. 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 | 4 | 1 | 6 | ||
| missense | 89 | 1 | 90 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 96 | 5 | 1 | 102 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055674.4 | 21 | MANE Select | |
| Ensembl | ENSP00000368994.5 | 21 | MANE Select | |
| RefSeq | NP_001308093.1 | 20 | Standard | |
| RefSeq | NP_001308095.1 | 20 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Rho GTPase cycle
- Signaling by Rho GTPases
Biological Process
- exocytosis
- signal transduction
- regulation of actin cytoskeleton organization
- negative regulation of Rac protein signal transduction
- positive regulation of GTPase activity
Molecular Function
- GTPase activator activity
- protein binding
- phospholipid binding
- Rac GTPase binding
Cellular Component
- cytosol
- postsynaptic density
- cell junction
- leading edge membrane
- dendritic spine
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000379672
- Coding exons
- 21
- Length
- 202105
- Individuals with no LoFs
- 124628
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 124638
- p
- 0.0000401
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.39 | 310 | 453 | 0.684 | 0.0000247 | 5274 |
| Missense (PolyPhen) | 25 | 93.216 | 0.26819 | 1149 | ||
| Synonymous | -1.51 | 211 | 185 | 1.14 | 0.0000113 | 1604 |
| Loss of Function | 5.73 | 5 | 47.7 | 0.105 | 0.00000265 | 517 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| 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) | 0.00011 | 0.000080 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: GTPase-activating protein (GAP) that stimulates the GTPase activity of Rho-type GTPases. Thereby, controls Rho-type GTPases cycling between their active GTP-bound and inactive GDP- bound states. May act as a GAP for CDC42 and RAC1. Endosomal recycling protein which, in association with SHANK3, is involved in synaptic plasticity. Promotes GRIA1 exocytosis from recycling endosomes and spine morphological changes associated to long-term potentiation. {ECO:0000269|PubMed:11431473}.;
Intolerance Scores
- RVIS EVS
- -1.49
- RVIS percentile EVS
- 3.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |