WHAMM
protein-codingWASP homolog associated with actin, golgi membranes and microtubules, the group of Wiskott-Aldrich Syndrome protein family
Gene summary
This gene encodes a protein that plays a role in actin nucleation, Golgi membrane association and microtubule binding. The encoded protein is a nucleation-promoting factor that regulates the Actin-related protein 2/3 complex. The activated complex initiates growth of new actin filaments by binding to existing actin filaments. The encoded protein also functions in regulation of transport from the endoplasmic reticulum to the Golgi complex and in maintenance of the Golgi complex near the centrosome. Four pseudogenes of this gene are present on the same arm of chromosome 15 as this gene. [provided by RefSeq, Aug 2013]
- WHDC1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~26.5 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 WHAMM variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001080435.3. 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 | 1 | 1 | 2 | |||
| missense | 144 | 6 | 1 | 151 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 145 | 7 | 2 | 154 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001073904.1 | 10 | MANE Select | |
| Ensembl | ENSP00000286760.4 | 10 | MANE Select | |
| Ensembl | ENSP00000614592.1 | 10 | Standard | |
| Ensembl | ENSP00000614592.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Tight junction - Homo sapiens (human)
Biological Process
- endoplasmic reticulum to Golgi vesicle-mediated transport
- actin filament organization
- cell cycle arrest
- lamellipodium assembly
- Arp2/3 complex-mediated actin nucleation
Molecular Function
- actin binding
- microtubule binding
- GTP-Rho binding
- Arp2/3 complex binding
Cellular Component
- Golgi membrane
- cytoplasm
- cytosol
- microtubule
- cytoplasmic vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000286760
- Coding exons
- 10
- Length
- 25232
- Individuals with no LoFs
- 124588
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 65
- Defined
- 124653
- p
- 0.000261
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.180 | 367 | 357 | 1.03 | 0.0000197 | 5142 |
| Missense (PolyPhen) | 120 | 115.82 | 1.0361 | 1700 | ||
| Synonymous | -1.40 | 161 | 140 | 1.15 | 0.00000793 | 1624 |
| Loss of Function | 0.931 | 22 | 27.2 | 0.808 | 0.00000147 | 404 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00026 | 0.00026 | rare |
| Latino/Admixed American | 0.00016 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00046 | 0.00039 | rare |
| Finnish | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.00020 | 0.00019 | rare |
| South Asian | 0.00069 | 0.00062 | rare |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a nucleation-promoting factor (NPF) that stimulates Arp2/3-mediated actin polymerization both at the Golgi apparatus and along tubular membranes. Its activity in membrane tubulation requires F-actin and interaction with microtubules. Proposed to use coordinated actin-nucleating and microtubule- binding activities of distinct WHAMM molecules to drive membrane tubule elongation; when MT-bound can recruit and remodel membrane vesicles but is prevented to activate the Arp2/3 complex. Involved as a regulator of Golgi positioning and morphology. Participates in vesicle transport between the reticulum endoplasmic and the Golgi complex. Required for RhoD-dependent actin reorganization such as in cell adhesion and cell migration. {ECO:0000269|PubMed:18614018, ECO:0000269|PubMed:23027905, ECO:0000269|PubMed:23087206}.;
Recessive Scores
- pRec
- 0.0950
Intolerance Scores
- LoFtool
- 0.899
- RVIS EVS
- 0.33
- RVIS percentile EVS
- 73.65
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.382
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |