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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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EFHC2
EF-hand domain containing 2
Chromosome X · Xp11.3
NCBI Gene: 80258Ensembl: ENSG00000183690.14HGNC: HGNC:26233UniProt: Q5JST6
33PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
axonemal microtubuleciliary basal bodyprotein bindingaxonemal A tubule inner sheathornithine carbamoyltransferase deficiencyopen-angle glaucomachildhood supratentorial ependymomaependymoma
✦AI Summary

EFHC2 (EF-hand domain containing 2) is an X-linked gene encoding a protein with calcium-binding EF-hand motifs and DM10 domains that functions as a microtubule inner protein in ciliary axonemes. The protein is required for motile cilia beating and flagellar motility [UniProt]. In zebrafish development, EFHC2 plays a crucial role in pronephros segmentation, specifically regulating distal nephron development and multi-ciliated cell formation 1. The gene has been investigated as a candidate for several neurological conditions. A tentative association was found between EFHC2 polymorphisms and juvenile myoclonic epilepsy in German males, particularly the S430Y variant in classical JME cases 2. However, a subsequent Turkish study found no association between the S430Y polymorphism and idiopathic generalized epilepsy 3. EFHC2 variants have also been associated with fear recognition and harm avoidance traits, with one intronic SNP accounting for over 3% of variance in harm avoidance behavior 4. Contiguous deletions involving EFHC2 may contribute to syndromic features, though one case study showed that EFHC2 deletion alone may not cause epilepsy 5. The gene remains a candidate for various neurological and developmental disorders requiring further investigation.

Sources cited
1
EFHC2 is crucial for pronephros segmentation and multi-ciliated cell development in zebrafish
PMID: 30349665
2
Tentative association found between S430Y polymorphism and juvenile myoclonic epilepsy in German males
PMID: 16112844
3
No association found between S430Y polymorphism and idiopathic generalized epilepsy in Turkish population
PMID: 26958022
4
EFHC2 variants associated with fear recognition and harm avoidance traits
PMID: 19429002
5
Contiguous deletion involving EFHC2 may not cause epilepsy based on case study
PMID: 29321361
Disease Associationsⓘ20
ornithine carbamoyltransferase deficiencyOpen Targets
0.12Weak
open-angle glaucomaOpen Targets
0.05Suggestive
childhood supratentorial ependymomaOpen Targets
0.03Suggestive
ependymomaOpen Targets
0.03Suggestive
glaucomaOpen Targets
0.02Suggestive
colorectal adenocarcinomaOpen Targets
0.02Suggestive
generalised epilepsyOpen Targets
0.02Suggestive
juvenile myoclonic epilepsyOpen Targets
0.01Suggestive
Turner syndromeOpen Targets
0.01Suggestive
Merkel cell skin cancerOpen Targets
0.01Suggestive
Norrie diseaseOpen Targets
0.01Suggestive
BlindnessOpen Targets
0.01Suggestive
myoclonic epilepsyOpen Targets
0.01Suggestive
X-linked intellectual disabilityOpen Targets
0.01Suggestive
cutaneous lupus erythematosusOpen Targets
0.01Suggestive
nasopharyngeal neoplasmOpen Targets
0.01Suggestive
epilepsyOpen Targets
0.01Suggestive
small cell lung carcinomaOpen Targets
0.01Suggestive
panic disorderOpen Targets
0.00Suggestive
systemic juvenile idiopathic arthritisOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TUBA1AProtein interaction91%TUBB4BProtein interaction91%SPACA9Protein interaction91%CFAP45Protein interaction91%RIBC2Protein interaction91%SPAG8Protein interaction91%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
65%
Ovary
21%
Brain
17%
Lung
6%
Liver
1%
Gene Interaction Network
Click a node to explore
EFHC2TUBA1ATUBB4BSPACA9CFAP45RIBC2SPAG8
PROTEIN STRUCTURE
Preparing viewer…
PDB2Z14 · 1.68 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.51Moderately Constrained
pLIⓘ
0.97Intolerant
Observed/Expected LoF0.34 [0.24–0.51]
RankingsWhere EFHC2 stands among ~20K protein-coding genes
  • #11,328of 20,598
    Most Researched33
  • #3,075of 17,882
    Most Constrained (LOEUF)0.51 · top quartile
Genes detectedEFHC2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Clinical exome sequencing findings in 1589 patients.
PMID: 36964972
Am J Med Genet A · 2023
1.00
2
No relation between EFHC2 gene polymorphism and Idiopathic generalized epilepsy.
PMID: 26958022
Afr Health Sci · 2015
0.90
3
Preliminary evidence of association between EFHC2, a gene implicated in fear recognition, and harm avoidance.
PMID: 19429002
Neurosci Lett · 2009
0.80
4
A novel contiguous deletion involving NDP, MAOB and EFHC2 gene in a patient with familial Norrie disease: bilateral blindness and leucocoria without other deficits.
PMID: 29321361
J Genet · 2017
0.70
5
Genetic polymorphisms and idiopathic generalized epilepsies.
PMID: 17765802
Pediatr Neurol · 2007
0.60