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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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EFHC1
EF-hand domain containing 1
Chromosome 6 Β· 6p12.2
NCBI Gene: 114327Ensembl: ENSG00000096093.17HGNC: HGNC:16406UniProt: B2CKC5
56PubMed Papers
22Diseases
0Drugs
1Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mitotic spindle organizationmitotic spindlecerebral cortex cell migrationspindle polejuvenile myoclonic epilepsyAbnormality of the skeletal systemlower respiratory tract diseasechronic obstructive pulmonary disease
✦AI Summary

EFHC1 (EF-hand domain containing 1) is a microtubule-associated protein with critical roles in neuronal development and cilia function. As a microtubule inner protein component of dynein-decorated doublet microtubules in cilia axoneme, EFHC1 is required for motile cilia beating 1. During cortical development, EFHC1 regulates cell division and neuronal migration by controlling microtubule dynamics 23. Loss of EFHC1 function disrupts mitotic spindle organization, impairs M-phase progression, and induces microtubule bundling, leading to radial migration defects in cortical progenitors 2. EFHC1 also negatively regulates neurite growth by fine-tuning microtubule cytoskeleton dynamics 4. Functionally, EFHC1 may enhance calcium influx through CACNA1E and stimulate programmed cell death 2. EFHC1 mutations are associated with juvenile myoclonic epilepsy (JME) and juvenile absence epilepsy, with pathogenic variants identified across diverse populations 53. However, population-specific genetic backgrounds influence penetrance, as some reportedly pathogenic mutations occur in healthy individuals, particularly in African and Hispanic populations 67. Recent reassessment suggests EFHC1 testing currently lacks sufficient scientific foundation for routine clinical diagnosis and should remain research-focused 7.

Sources cited
1
EFHC1 is a microtubule inner protein component of dynein-decorated doublet microtubules in cilia axoneme required for motile cilia beating
PMID: 36191189
2
EFHC1 is a microtubule-associated protein regulating cell division and cortical development; loss of function disrupts mitotic spindle organization and causes radial migration defects
PMID: 19734894
3
EFHC1 mutations cause microtubule-related abnormalities during cell division and account for ~6% of JME patients in Indian population
PMID: 28370826
4
EFHC1 homologue Defhc1.1 functions as negative regulator of microtubule dynamics and inhibitor of neurite growth; EFHC1-dependent JME may result from augmented spontaneous neurotransmitter release
PMID: 21835885
5
R182H EFHC1 mutation is common variant in JME; 3'UTR variant may have protective role against JME in Turkish population
PMID: 38088014
6
Reportedly pathogenic EFHC1 mutations found in healthy individuals from multiple ethnic backgrounds, suggesting genetic background influences disease expression
PMID: 25489633
7
EFHC1 testing lacks sufficient scientific foundation for routine clinical diagnosis of JME and should be limited to research purposes
PMID: 33181902
Disease Associationsβ“˜22
juvenile myoclonic epilepsyOpen Targets
0.79Strong
Abnormality of the skeletal systemOpen Targets
0.44Moderate
lower respiratory tract diseaseOpen Targets
0.31Weak
chronic obstructive pulmonary diseaseOpen Targets
0.31Weak
Abruptio PlacentaeOpen Targets
0.29Weak
Generalized non-motor (absence) seizureOpen Targets
0.28Weak
ovarian dysfunctionOpen Targets
0.24Weak
Typical absence seizureOpen Targets
0.19Weak
myoclonic epilepsyOpen Targets
0.09Suggestive
infantile spasmsOpen Targets
0.07Suggestive
generalised epilepsyOpen Targets
0.07Suggestive
Familial cortical myoclonusOpen Targets
0.07Suggestive
hereditary geniospasmOpen Targets
0.07Suggestive
Unverricht-Lundborg diseaseOpen Targets
0.07Suggestive
benign adult familial myoclonic epilepsyOpen Targets
0.06Suggestive
Myoclonus - cerebellar ataxia - deafnessOpen Targets
0.06Suggestive
myoclonus-cerebellar ataxia-deafness syndromeOpen Targets
0.06Suggestive
intellectual disability, autosomal recessive 6Open Targets
0.06Suggestive
Progressive myoclonic epilepsyOpen Targets
0.06Suggestive
Unverricht-Lundborg syndromeOpen Targets
0.06Suggestive
Juvenile absence epilepsy 1UniProt
Juvenile myoclonic epilepsy 1UniProt
Pathogenic Variants1
NM_018100.4(EFHC1):c.1314del (p.Phe438fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2015β†’ Residue 438
View on ClinVar β†—
Related Genes
PAQR8Protein interaction94%CACNB4Protein interaction92%CLCN2Protein interaction92%GABRA1Protein interaction92%GABRDProtein interaction92%WDR90Protein interaction91%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
56%
Brain
41%
Lung
35%
Heart
33%
Liver
27%
Gene Interaction Network
Click a node to explore
EFHC1PAQR8CACNB4CLCN2GABRA1GABRDWDR90
PROTEIN STRUCTURE
Preparing viewer…
PDB7UNG Β· 3.60 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.91LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.72 [0.58–0.91]
RankingsWhere EFHC1 stands among ~20K protein-coding genes
  • #8,061of 20,598
    Most Researched56
  • #5,064of 5,498
    Most Pathogenic Variants1
  • #8,218of 17,882
    Most Constrained (LOEUF)0.91
Genes detectedEFHC1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
EFHC1 gene mutation profile of Turkish JME patients and its association with disease risk.
PMID: 38088014
Seizure Β· 2024
1.00
2
Defhc1.1, a homologue of the juvenile myoclonic gene EFHC1, modulates architecture and basal activity of the neuromuscular junction in Drosophila.
PMID: 21835885
Hum Mol Genet Β· 2011
0.90
3
Exclusion of the juvenile myoclonic epilepsy gene EFHC1 as the cause of migraine on chromosome 6, but association to two rare polymorphisms in MEP1A and RHAG.
PMID: 16378686
Neurosci Lett Β· 2006
0.80
4
Pathogenic EFHC1 mutations are tolerated in healthy individuals dependent on reported ancestry.
PMID: 25489633
Epilepsia Β· 2015
0.70
5
Microtubule-associated defects caused by EFHC1 mutations in juvenile myoclonic epilepsy.
PMID: 28370826
Hum Mutat Β· 2017
0.60