EFHC1 R182H - GET-Evidence



(EFHC1 Arg182His)

Short summary

Probably benign. OMIM appears to incorrectly interpret literature as linking this variant to juvenile myoclonic epilepsy; the authors report it as a polymorphism.

Variant evidence
Computational 1

Polyphen 2 predicts benign effect

Functional 1

No functional effect

See Suzuki T et al. 2004 (15258581).

Case/Control 3

Fairly common in the population (Suzuki et al’s controls were 11%)

See Suzuki T et al. 2004 (15258581).

Familial -
Clinical importance
Severity -
Treatability -
Penetrance -


Low clinical importance, Likely benign

(The "low clinical importance, likely" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern


Summary of published research, and additional commentary


Allele frequency

  • A @ chr6:52303361: 4.4% (473/10758) in EVS
  • A @ chr6:52411319: 7.0% (9/128) in GET-Evidence
  • Frequency shown in summary reports: 4.4% (473/10758)


Liu AW, Delgado-Escueta AV, Serratosa JM, Alonso ME, Medina MT, Gee MN, Cordova S, Zhao HZ, Spellman JM, Peek JR, et al. Juvenile myoclonic epilepsy locus in chromosome 6p21.2-p11: linkage to convulsions and electroencephalography trait. Am J Hum Genet. 1995 Aug;57(2):368-81. PubMed PMID: 7668263; PubMed Central PMCID: PMC1801565.

LA-Belize family is described with linkage in this region, with a peak LOD of around 3.5-3.6.

Suzuki T, Delgado-Escueta AV, Aguan K, Alonso ME, Shi J, Hara Y, Nishida M, Numata T, Medina MT, Takeuchi T, Morita R, Bai D, Ganesh S, Sugimoto Y, Inazawa J, Bailey JN, Ochoa A, Jara-Prado A, Rasmussen A, Ramos-Peek J, Cordova S, Rubio-Donnadieu F, Inoue Y, Osawa M, Kaneko S, Oguni H, Mori Y, Yamakawa K. Mutations in EFHC1 cause juvenile myoclonic epilepsy. Nat Genet. 2004 Aug;36(8):842-9. Epub 2004 Jul 18. PubMed PMID: 15258581.

These authors describe mutations in this gene linked to juvenile myoclonic epilepsy. They also note several coding polymorphism, R159W, R182H and I619L — this variant (182H) had an allele frequency of 11%. They note that the R182H polymorphism segregates with disease in the LA-Belize family, but this not surprising as the family was already known to have linkage in this region.

The authors do not appear to interpret this variant as disease-causing, as they report no effect in functional studies in this manner: “Mutations associated with JME (P77T/R221H, P77T, D210N, R221H, F229L, D253Y) significantly reversed the cell-death effect of EFHC1 at 36 and 48 h after transfection, whereas the polymorphisms that occurred both in individuals affected with JME and in controls (R159W, R182H, I619L) largely maintained the cell-death effects.” OMIM appears to have incorrectly referenced this paper as suggesting that the variant causes susceptibility to juvenile myoclonic epilepsy.



hu0D879F - CGI sample GS00253-DNA_G01_200_37
het A @ chr6:52303361






hu9385BA - CGI sample GS00253-DNA_E01_200_37
het A @ chr6:52303361




huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het A @ chr6:52303361


GS06985 - var-GS06985-1100-36-ASM
het A @ chr6:52411320


GS07357 - var-GS07357-1100-36-ASM
het A @ chr6:52411320


GS19669 - var-GS19669-1100-36-ASM
het A @ chr6:52411320


GS20502 - var-GS20502-1100-36-ASM
het A @ chr6:52411320


Other external references

  • rs3804505
  • Score: 0.038 (benign)
    Web search results (44 hits -- see all)
  • Heterogeneity at the JME 6p11-12 locus: absence of mutations ...
    PURPOSE: The EFHC1 gene, encoding a protein with a Ca(2+)-sensing EF-hand motif, ... The EFHC1 variants reported in Mexican families may be mendelian ...
  • Heterogeneity at the JME 6p11–12 Locus: Absence of Mutations ...
    Heterogeneity at the JME 6p11–12 Locus: Absence of Mutations in the EFHC1 Gene in Linked Dutch Families ... 146_147delGC), nonsynonymous (R159W, R182H, M448T, I619L), intronic ...
  • 若年性ミオクロニーてんかん原因遺伝子の発見
    また、JME患者だけでなく正常コントロールでもある一定の割合で見つかるR159W, R182H, I619Lの3種の多型も見いだされました。 EFHC1はカルシウムイオン結合モチーフを持つ640アミノ酸からなる新規蛋白をコードします(図1a)。発現は広い範囲の組織でみられ(図1c)、脳 ...
  • Human Genetics. Epilepsia 46:365 (2005)
    Human Genetics. Epilepsia 46:365 (2005) ... 262 AN ASSOCIATION STUDY ON JUVENILE MYOCLONIC EPILEPSY AND EFHC1 POLYMORPHISMS 1Dongsheng Bai, 1,2Julia N. Bailey, 3Maria E. ...
  • BSIでの研究成果:若年性ミオクロニーてんかん原因遺伝子の発見 - 理研BSIニュース No. 29(2005年8月号 ...
    研究チームは、米国カリフォルニア大学ロサンゼルス校との共同研究により、最も発症数の多いてんかんである若年性ミオクロニーてんかん(JME)の原因遺伝子EFHC1を発見しました。 ... また、JME患者だけでなく正常コントロールでもある一定の割合で見つかるR159W、 R182H、 I619Lの3種の多型も見出されました。 ...
  • 神経遺伝研究 チ ー ム
    る R159W,R182H,I619L の 3 種の多型も見いだされた。 EFHC1 はカルシウムイオン結合モチーフを持つ 640 アミ. ノ酸からなる新規タンパクをコードする。 ... the EFHC1 protein overlapped in the mouse brain, the. EFHC1 protein increased current ...
  • Heterogeneity at the JME 6p11-12 locus: absence of mutations ...
    PURPOSE: The EFHC1 gene, encoding a protein with a Ca(2+)-sensing EF-hand motif, is localized at 6p12 and was recently reported as mutated in six ...
  • Trenité, DGAKN (Dorothée G A Kasteleijn-Nolst)
    Trenité, DGAKN (Dorothée G A Kasteleijn-Nolst) :: Genome-wide linkage scan of epilepsy-related photoparoxysmal electroencephalographic response: evidence for ...
  • EFHC1, a protein mutated in juvenile myoclonic epilepsy ...
    BioInfoBank Library :: EFHC1, a protein mutated in juvenile myoclonic epilepsy, associates with the mitotic spindle through its N-terminus. Molecular characterization ...
  • A Multiplex Human Syndrome Implicates a Key Role for ...
    EFHC1. EF-hand domain (C') containing 1. 11. E3, c.190C>T. n/a. CGG-R; TGG ... CGC-R; CAC-H; R182H; this is a benign change (Polyphen)** U:GG, A:GG, ...

Other in silico analyses

  • NBLOSUM100 score = 1
  • GET-Evidence autoscore = 3

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Gene search

"GENE" or "GENE A123C":

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