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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ELMOD3
ELMO domain containing 3
Chromosome 2 · 2p11.2
NCBI Gene: 84173Ensembl: ENSG00000115459.19HGNC: HGNC:26158UniProt: Q96FG2
29PubMed Papers
22Diseases
0Drugs
1Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GTPase activator activityprotein bindingcilium assemblyGolgi apparatushearing loss, autosomal recessivedeafnesssubarachnoid hemorrhageautosomal dominant nonsyndromic hearing loss
✦AI Summary

ELMOD3 (ELMO domain containing 3) is a GTPase-activating protein (GAP) that primarily regulates ARL2 and ARF family GTPases 1. The protein localizes to the Golgi apparatus and cilia, where it regulates ciliogenesis and ciliary protein trafficking 2. ELMOD3 functionally associates with the actin cytoskeleton in cochlear hair cell stereocilia 1, where it is essential for maintaining proper F-actin dynamics and stereocilia morphology 3. Pathogenic variants in ELMOD3 cause both autosomal dominant and recessive nonsyndromic hearing loss (DFNA81 and DFNB88) 41. The c.512A>G (p.His171Arg) missense variant produces unstable protein with abnormal subcellular localization and accelerated protein degradation, leading to late-onset progressive hearing loss 4. Elmod3 knockout mice exhibit progressive hearing loss from 2 months of age with shortened, fused inner hair cell stereocilia and outer hair cell degeneration 3. Transcriptomic analysis of patient-derived iPSCs carrying the ELMOD3 mutation reveals dysregulation of genes involved in sensory epithelial development, intermediate filament organization, and ion transport 5. Beyond hearing, copy number deletions encompassing ELMOD3 have been associated with autism spectrum disorder through generation of chimeric ELMOD3-SH2D6 transcripts 6. Recent evidence suggests ELMOD3 may promote gastric cancer proliferation through β-catenin signaling 7, indicating broader pathogenic roles beyond auditory function.

Sources cited
1
ELMOD3 c.512A>G (p.His171Arg) identified as causative variant for autosomal dominant nonsyndromic hearing loss; variant causes abnormal protein expression, subcellular localization, and reduced protein stability
PMID: 29713870
2
ELMOD3 is a GTPase-activating protein for ARL2; c.794T>C (p.Leu265Ser) mutation associated with autosomal recessive deafness (DFNB88); ELMOD3 localizes to stereocilia and associates with actin cytoskeleton
PMID: 24039609
3
Elmod3 knockout mice develop progressive hearing loss from 2 months age with stereocilia dysmorphologies (shortening, fusion) and reduced F-actin expression in cochlear hair cells
PMID: 31628468
4
ELMOD3 functions as ARF/ARL GAP at Golgi and cilia; required for ciliogenesis and ciliary protein trafficking from Golgi to cilia
PMID: 34818063
5
Patient iPSCs with ELMOD3 c.512A>G show dysregulated genes in sensory epithelial development, intermediate filament organization, and ion transport
PMID: 37708136
6
2p11.2 microdeletion encompassing ELMOD3 generates chimeric ELMOD3-SH2D6 fusion transcript associated with autism spectrum disorder
PMID: 31800155
7
ELMOD3 promotes gastric cancer cell proliferation and migration through interactions with β-catenin signaling and F-actin cytoskeleton
PMID: 39621020
Disease Associationsⓘ22
hearing loss, autosomal recessiveOpen Targets
0.48Moderate
deafnessOpen Targets
0.40Weak
subarachnoid hemorrhageOpen Targets
0.26Weak
autosomal dominant nonsyndromic hearing lossOpen Targets
0.20Weak
hearing loss, autosomal dominant 81Open Targets
0.18Weak
respiratory tract infectious disorderOpen Targets
0.12Weak
attention deficit hyperactivity disorderOpen Targets
0.09Suggestive
attention deficit-hyperactivity disorder 8Open Targets
0.07Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.07Suggestive
intellectual disability, autosomal recessive 59Open Targets
0.07Suggestive
movement disorderOpen Targets
0.07Suggestive
schizophrenia 15Open Targets
0.07Suggestive
autismOpen Targets
0.05Suggestive
Phelan-McDermid syndromeOpen Targets
0.05Suggestive
Tourette syndromeOpen Targets
0.05Suggestive
X-linked non-syndromic intellectual disabilityOpen Targets
0.04Suggestive
intellectual disability, autosomal dominant 50Open Targets
0.04Suggestive
Potocki-Lupski syndromeOpen Targets
0.04Suggestive
hearing loss, autosomal dominant 87Open Targets
0.04Suggestive
FRAXE intellectual disabilityOpen Targets
0.04Suggestive
Deafness, autosomal dominant, 81UniProt
Deafness, autosomal recessive, 88UniProt
Pathogenic Variants1
NM_001135022.2(ELMOD3):c.794T>C (p.Leu265Ser)Pathogenic
Autosomal recessive nonsyndromic hearing loss 88
★☆☆☆2021→ Residue 265
View on ClinVar ↗
Related Genes
CIBAR2Shared pathway100%CFAP184Shared pathway100%HYLS1Shared pathway100%LRRC45Shared pathway100%WDR90Shared pathway100%PTPDC1Shared pathway100%
Tissue Expression6 tissues
Liver
100%
Ovary
88%
Lung
83%
Bone Marrow
61%
Heart
48%
Brain
26%
Gene Interaction Network
Click a node to explore
ELMOD3CIBAR2CFAP184HYLS1LRRC45WDR90PTPDC1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96FG2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.02LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.75 [0.56–1.02]
RankingsWhere ELMOD3 stands among ~20K protein-coding genes
  • #12,136of 20,598
    Most Researched29
  • #5,267of 5,498
    Most Pathogenic Variants1
  • #10,032of 17,882
    Most Constrained (LOEUF)1.02
Genes detectedELMOD3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
ELMOD3, a novel causative gene, associated with human autosomal dominant nonsyndromic and progressive hearing loss.
PMID: 29713870
Hum Genet · 2018
1.00
2
Gene regulation analysis of patient-derived iPSCs and its CRISPR-corrected control provides a new tool for studying perturbations of ELMOD3 c.512A>G mutation during the development of inherited hearing loss.
PMID: 37708136
PLoS One · 2023
0.90
3
ELMOD3-SH2D6 gene fusion as a possible co-star actor in autism spectrum disorder scenario.
PMID: 31800155
J Cell Mol Med · 2020
0.80
4
Elmod3 knockout leads to progressive hearing loss and abnormalities in cochlear hair cell stereocilia.
PMID: 31628468
Hum Mol Genet · 2019
0.70
5
The ARF GAPs ELMOD1 and ELMOD3 act at the Golgi and cilia to regulate ciliogenesis and ciliary protein traffic.
PMID: 34818063
Mol Biol Cell · 2022
0.60