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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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WHAMM
WASP homolog associated with actin, golgi membranes and microtubules
Chromosome 15 · 15q25.2
NCBI Gene: 123720Ensembl: ENSG00000156232.8HGNC: HGNC:30493UniProt: Q8TF30
21PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
microtubule bindingsmall GTPase bindingcytosolArp2/3 complex bindingovarian neoplasmtype 2 diabetes mellitusprimary ovarian insufficiencysarcoidosis
✦AI Summary

WHAMM is a nucleation-promoting factor that stimulates Arp2/3 complex-mediated actin polymerization at the Golgi apparatus and along tubular membranes 1. It coordinates actin-nucleating and microtubule-binding activities to drive membrane tubule elongation and regulate Golgi positioning 2. WHAMM participates in vesicle transport between the endoplasmic reticulum and Golgi complex and is required for RhoD-dependent actin reorganization in cell adhesion and migration. At the cellular level, WHAMM controls autophagosome membrane closure and cargo sequestration through Arp2/3 complex-mediated actin assembly 3. It also regulates cell death by controlling actin-mediated cytochrome c release from mitochondria and ASC speck formation 4. WHAMM forms a complex with RHOD to facilitate ATG9A trafficking and autophagosome formation during starvation 5. Additionally, WHAMM and JMY are necessary for rapid DNA damage-induced apoptosis through a p53-dependent pathway 6. Clinically, WHAMM is identified as a key kidney disease risk gene; variants on chromosome 15 regulate WHAMM expression, which is elevated in chr15 and acute kidney disease 4. WHAMM knockout mice display kidney proximal tubule abnormalities and impaired nutrient reabsorption, with elevated urinary albumin, glucose, phosphate, and amino acids 3. These findings reveal WHAMM's essential role in maintaining kidney function and controlling cellular proteostasis.

Sources cited
1
WHAMM is identified as a kidney disease risk gene; variants regulate WHAMM expression which is elevated in kidney disease; WHAMM controls cell death by regulating actin-mediated cytochrome c release and ASC speck formation
PMID: 40138314
2
WHAMM is a nucleation-promoting factor that activates Arp2/3 complex and shares a WCA module with other NPFs
PMID: 20888769
3
WHAMM knockout mice show nutrient reabsorption defects and kidney proximal tubule abnormalities; WHAMM controls autophagosomal membrane closure and cargo receptor recruitment
PMID: 38328079
4
WHAMM forms a complex with RHOD and participates in RhoD-dependent ATG9A trafficking to promote autophagosome formation
PMID: 40143438
5
Rab1 recruits WHAMM to membrane tubules but inhibits WHAMM-mediated actin nucleation
PMID: 26823012
6
WHAMM is necessary for rapid DNA damage-induced apoptosis through mitochondrial permeabilization and caspase activation
PMID: 33872315
Disease Associationsⓘ20
ovarian neoplasmOpen Targets
0.33Weak
type 2 diabetes mellitusOpen Targets
0.16Weak
primary ovarian insufficiencyOpen Targets
0.12Weak
sarcoidosisOpen Targets
0.11Weak
breast ductal adenocarcinomaOpen Targets
0.11Weak
focal segmental glomerulosclerosisOpen Targets
0.07Suggestive
nephrotic syndromeOpen Targets
0.07Suggestive
familial idiopathic steroid-resistant nephrotic syndromeOpen Targets
0.07Suggestive
cardiac arrestOpen Targets
0.07Suggestive
hyperprolinemia type 1Open Targets
0.06Suggestive
primary Fanconi syndromeOpen Targets
0.06Suggestive
Dent diseaseOpen Targets
0.06Suggestive
morbid obesityOpen Targets
0.06Suggestive
Seizures - intellectual disability due to hydroxylysinuriaOpen Targets
0.06Suggestive
seizures-intellectual disability due to hydroxylysinuria syndromeOpen Targets
0.06Suggestive
carnosinemiaOpen Targets
0.06Suggestive
IGA glomerulonephritisOpen Targets
0.06Suggestive
Fanconi renotubular syndrome 1Open Targets
0.05Suggestive
nail-patella-like renal diseaseOpen Targets
0.05Suggestive
carnitine palmitoyl transferase II deficiency, myopathic formOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ACTBProtein interaction98%ACTG1Protein interaction93%ACTR3Protein interaction92%ACTR3BProtein interaction92%WASF1Protein interaction92%HCLS1Protein interaction91%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
29%
Lung
29%
Ovary
26%
Brain
16%
Heart
16%
Gene Interaction Network
Click a node to explore
WHAMMACTBACTG1ACTR3ACTR3BWASF1HCLS1
PROTEIN STRUCTURE
Preparing viewer…
PDB5X1G · 4.50 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.22LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.95 [0.75–1.22]
RankingsWhere WHAMM stands among ~20K protein-coding genes
  • #14,065of 20,598
    Most Researched21
  • #12,846of 17,882
    Most Constrained (LOEUF)1.22
Genes detectedWHAMM
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The actin and microtubule network regulator WHAMM is identified as a key kidney disease risk gene.
PMID: 40138314
Cell Rep · 2025
1.00
2
WASH, WHAMM and JMY: regulation of Arp2/3 complex and beyond.
PMID: 20888769
Trends Cell Biol · 2010
0.90
3
WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration.
PMID: 38328079
bioRxiv · 2024
0.80
4
WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration.
PMID: 38598293
Mol Biol Cell · 2024
0.70
5
RHOD mediates ATG9A trafficking to promote autophagosome formation during autophagy in cancer.
PMID: 40143438
Autophagy · 2025
0.60