Human Disease Model Report: epilepsy, generalized, with febrile seizures plus, type 2

General Information

Name

epilepsy, generalized, with febrile seizures plus, type 2

FlyBase ID

FBhh0000309

Disease Ontology Term

generalized epilepsy with febrile seizures plus 2

Parent Disease

epilepsy, generalized, with febrile seizures plus

OMIM

GENERALIZED EPILEPSY WITH FEBRILE SEIZURES PLUS, TYPE 2; GEFSP2

Overview

Generalized epilepsy with febrile seizures plus, type 2 (GEFSP2 or GEFS+) is one of several diseases associated with defects in the human gene SCN1A; GEFSP2 is inherited as an autosomal dominant. This gene is one of multiple sodium channel alpha subunits in human; there is one orthologous gene in flies, Dmel\para. OMIM includes this disease in the phenotypic series epilepsy, generalized, with febrile seizures plus (FBhh0000300).

A mutational lesion of Dmel\para analogous to one implicated in this disease (K1270T in the human SCN1A gene) has been studied as a model of GEFSP2 in Drosophila. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): the endogenous para gene was modified, thus affecting multiple isoforms (corresponds to K1270T in the human SCN1A gene, designated para^GEFS+). See also the human disease model report for epilepsy, SCN-alpha-related (FBhh0000289).

[updated Jul. 2017 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: epilepsy, generalized, with febrile seizures plus

Symptoms and phenotype

Specific Disease Summary: epilepsy, generalized, with febrile seizures plus, type 2

OMIM report

[GENERALIZED EPILEPSY WITH FEBRILE SEIZURES PLUS, TYPE 2; GEFSP2](https://omim.org/entry/604403)

Human gene(s) implicated

[SODIUM VOLTAGE-GATED CHANNEL, ALPHA SUBUNIT 1; SCN1A](https://omim.org/entry/182389)

Symptoms and phenotype

Mutations in the SCN1A gene cause a spectrum of seizure disorders. Patients with isolated febrile seizures usually show spontaneous remission by age 6 years, whereas patients with GEFSP2 (also known as GEFS+) continue to have various types of febrile and afebrile seizures later in life. EIEE6, or Dravet syndrome, is the most severe phenotype associated with SCN1A mutations. [from MIM:604403; 2016.09.26]

(OMIM, 2013-)

Genetics

Generalized epilepsy with febrile seizures plus, type 2 (GEFSP2) is caused by heterozygous mutation in the SCN1A gene (autosomal dominant). [from MIM:604403; 2016.09.26]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

"SCN1A" stands for sodium channel, neuronal type I, alpha subunit. Voltage-sensitive sodium channels are heteromeric complexes consisting of a large central pore-forming glycosylated alpha subunit and 2 smaller auxiliary beta subunits. [from MIM:182389; 2016.09.26]

(OMIM, 2013-)

External links

Gene2Function (human gene): SCN1A
Gene Cards: SCN1A
GeneReviews, NCBI Bookshelf: SCN1A-Related Seizure Disorders
MedlinePlus (gene): SCN1A
MARRVEL (human gene): SCN1A
NCBI MedGen: Generalized epilepsy with febrile seizures plus, type 1 (GEFSP1)
NCBI (Entrez) gene: SCN1A; sodium voltage-gated channel alpha subunit 1

Disease synonyms

febrile seizures, familial, 3A

GEFS+

GEFS+2

GEFS+, type 2

GEFSP2

Related Diseases

Related human health report(s)

epilepsy, SCN-alpha-related

Related Specific Diseases

OMIM phenotypic series

Epilepsy, generalized, with febrile seizures plus

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[GEFSP2](https://omim.org/entry/604403)

[SCN1A](https://omim.org/entry/182389)

epilepsy, generalized, with febrile seizures plus, type 2

[GEFSP7](https://omim.org/entry/613863)

epilepsy, generalized, with febrile seizures plus, type 7

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

SCN1A; sodium voltage-gated channel alpha subunit 1

D. melanogaster ortholog (based on DIOPT)

Dmel\para

(DIOPT, 2013-)

Dmel\para

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\para

Gene Snapshot

paralytic (para) is an essential gene required for locomotor activity. It encodes an α-subunit of voltage-gated sodium channels. It is required for generation of sodium-dependent action potentials. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

NAV-A

Comments on ortholog(s)

Highest-scoring fly ortholog for human voltage-gated sodium channel alpha subunits encoded by ten different genes, including several associated with forms of epilepsy (SCN1A, SCN2A, SCN8A, SCN9A). Dmel\para shares 44-46% identity and 61-62% similarity with these human genes.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (3 groups)

para

RNA-protein

Interacting group

Assay

References

para - mle

anti tag coimmunoprecipitation, full identification by RNA sequencing

(Müller et al., 2020)

para - pum

pull down, anti tag western blot, anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Muraro et al., 2008)

para - Zn72D

anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Sapiro et al., 2020)

Alleles Reported to Model Human Disease (Disease Ontology) (15 alleles)

para

Models Based on Experimental Evidence ( 12 )

Allele

Disease

Evidence

References

para^HMS00868

model of epilepsy

CEA

(Zhang et al., 2022, Wang et al., 2021)

para^ts115

model of epilepsy

CEA with para^ts1

(Fergestad et al., 2006)

para^ts1

model of epilepsy

CEA

(Fergestad et al., 2006)

CEA with para^ts115

(Fergestad et al., 2006)

para^unspecified

model of epilepsy

CEA

(Kuebler and Tanouye, 2002)

para^GEFS+

model of generalized epilepsy with febrile seizures plus

CEA

(Petruccelli et al., 2015, Sun et al., 2012)

model of Dravet syndrome

CEA

(Schutte et al., 2014)

model of generalized epilepsy with febrile seizures plus 2

CEA

(Mituzaite et al., 2021, Chen et al., 2020)

model of epilepsy

CEA

(Byers et al., 2021)

para^DS.S1231R

model of epilepsy

CEA

(Kaas et al., 2016)

model of Dravet syndrome

CEA

(Mituzaite et al., 2021, Chen et al., 2020, Schutte et al., 2014)

para^Shu

model of epilepsy

CEA

(Chen et al., 2020, Kaas et al., 2016)

para^Shu.UAS

model of epilepsy

CEA

(Kaas et al., 2016)

para^R-C

model of Dravet syndrome

CEA

(Roemmich et al., 2021)

para^R-H

model of generalized epilepsy with febrile seizures plus 2

CEA

(Roemmich et al., 2021)

para^KO.attP

model of epilepsy

CEA

(Tapia et al., 2021)

model of Dravet syndrome

CEA

(Tapia et al., 2021)

Modifiers Based on Experimental Evidence ( 8 )

Allele

Disease

Interaction

References

para^GD3392

ameliorates epilepsy

modeled by para^Shu

(Kaas et al., 2016)

exacerbates developmental and epileptic encephalopathy 64

modeled by RhoBTB^UAS.cSa

(Langhammer et al., 2025)

exacerbates Huntington's disease

modeled by Hsap\HTT^{128Q.1-336.UAS}

(Al-Ramahi et al., 2018)

para^ts115

ameliorates epilepsy

modeled by para^Shu

(Kaas et al., 2016)

para^KK108534

ameliorates chromosome 16p11.2 deletion syndrome, 593-kb

modeled by CG10465^KK105756

(Iyer et al., 2018)

exacerbates brain cancer

modeled by Ras85D^V12.cUa.UAS, scrib⁶⁷³

(Manzanero-Ortiz et al., 2021)

para^ts1

ameliorates epilepsy

modeled by para^Shu

(Kaas et al., 2016)

model of epilepsy

is exacerbated by Atpα^DTS1

(Fergestad et al., 2006)

para^bss1

model of epilepsy

is ameliorated by shi^{ts1.IVS.p10.20xUAS}

(Kroll et al., 2015)

is ameliorated by Rab9^{Q71L.UASp.YFP}

(Kroll et al., 2015)

is ameliorated by Rab30^{Q66L.UASp.YFP}

(Kroll et al., 2015)

is ameliorated by Rab30^{T21N.UASp.YFP}

(Kroll et al., 2015)

is ameliorated by Rab32^{T33N.UASp.YFP}

(Kroll et al., 2015)

is ameliorated by Rab35^S22N.UAS.YFP

(Kroll et al., 2015)

is ameliorated by shi^1.UAS

(Kroll et al., 2015)

is ameliorated by Rab5^{Q88L.UASp.YFP}

(Kroll et al., 2015)

is ameliorated by Rab8^{T22N.UASp.YFP}

(Kroll et al., 2015)

is ameliorated by Rab9^{S26N.UASp.YFP}

(Kroll et al., 2015)

is ameliorated by shi¹

(Kroll et al., 2015)

is ameliorated by cac^TS2

(Saras and Tanouye, 2016)

is ameliorated by pum^UAS.cSa

(Lin et al., 2017)

is exacerbated by pum^KK109048

(Lin et al., 2017)

is ameliorated by tipE¹

(Parker et al., 2011)

is ameliorated by gish^GD10588

(Howlett et al., 2013)

is exacerbated by chn^KK105251

(Howlett et al., 2013)

is ameliorated by gish⁰⁴⁸⁹⁵

(Howlett et al., 2013)

is ameliorated by kcc^UAS.cHb

(Hekmat-Scafe et al., 2010)

is exacerbated by SLO2^CRISPR

(Byers et al., 2021)

is exacerbated by SLO2^DN.UAS

(Byers et al., 2021)

is ameliorated by Adcy1^rut-1

(Saras and Tanouye, 2016)

is ameliorated by GstS1^M26

(Chen et al., 2020)

ameliorates epilepsy

modeled by para^Shu

(Kaas et al., 2016)

modeled by eas²

(Kroll and Tanouye, 2013)

para^UAS.1-1

exacerbates developmental and epileptic encephalopathy 64

modeled by RhoBTB^UAS.cSa

(Langhammer et al., 2025)

para^GEFS+

exacerbates epilepsy

modeled by para^Shu

(Kaas et al., 2016)

model of epilepsy

is exacerbated by SLO2^CRISPR

(Byers et al., 2021)

is ameliorated by GstS1^M26

(Chen et al., 2020)

para^Shu

model of epilepsy

is ameliorated by para^ts115

(Kaas et al., 2016)

is ameliorated by para^ts1

(Kaas et al., 2016)

is ameliorated by para^bss1

(Kaas et al., 2016)

is exacerbated by para^GEFS+

(Kaas et al., 2016)

is ameliorated by para^GD3392

(Kaas et al., 2016)

is ameliorated by GstS1^GD16335

(Chen et al., 2020)

is ameliorated by GstS1^M26

(Chen et al., 2020)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

y¹ v¹; P{TRiP.JF01245}attP2/TM3, Sb¹

para^JF01469

P{TRiP.JF01469}

y¹ v¹; P{TRiP.JF01469}attP2

para^HMS00868

P{TRiP.HMS00868}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00868}attP2/TM3, Sb¹

para^GD3392

P{GD3392}

w¹¹¹⁸; P{GD3392}v6131

y¹ v¹; P{TRiP.JF01245}attP2/TM3, Sb¹

para^JF01469

P{TRiP.JF01469}

y¹ v¹; P{TRiP.JF01469}attP2

para^HMS00868

P{TRiP.HMS00868}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00868}attP2/TM3, Sb¹

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

para^hd5

amorphic allele - genetic evidence

PM hybrid dysgenesis

para^lk5

amorphic allele - genetic evidence

para^ID30

amorphic allele - genetic evidence

para^lk2

amorphic allele - genetic evidence

para^unspecified

para^A

amorphic allele - genetic evidence

ethyl methanesulfonate

y¹ w^* para^A P{neoFRT}19A/FM7c, P{GAL4-Kr.C}DC1, P{UAS-GFP.S65T}DC5, sn⁺

para^B

amorphic allele - genetic evidence

ethyl methanesulfonate

y¹ w^* para^B P{neoFRT}19A/FM7c, P{GAL4-Kr.C}DC1, P{UAS-GFP.S65T}DC5, sn⁺

para^{MI08578-FlpStop.D}

amorphic allele - genetic evidence

phiC31 integrase

y¹ w^* Mi{FlpStop}para^{MI08578-FlpStop.D}/FM7c

para^ko

amorphic allele - molecular evidence

FLPase

para^{MI08578-TG4.0}

amorphic allele - genetic evidence

phiC31 integrase

y¹ w^67c23 Mi{Trojan-GAL4.0}para^{MI08578-TG4.0}/FM7c

para^hd5

amorphic allele - genetic evidence

PM hybrid dysgenesis

para^ts115

ethyl methanesulfonate

para^R-C

CRISPR/Cas9

para^R-H

CRISPR/Cas9

para^KO.attP

amorphic allele - genetic evidence

gene targeting by homologous recombination

para^ts1

ethyl methanesulfonate

para^ts1/C(1)DX, y¹ f¹

para^lk5

amorphic allele - genetic evidence

para^Shu

ethyl methanesulfonate

para^bss1

para^ID30

amorphic allele - genetic evidence

para^lk2

amorphic allele - genetic evidence

para^unspecified

para^GEFS+

ends-out gene targeting

para^DS.S1231R

ends-out gene targeting

para^A

amorphic allele - genetic evidence

ethyl methanesulfonate

y¹ w^* para^A P{neoFRT}19A/FM7c, P{GAL4-Kr.C}DC1, P{UAS-GFP.S65T}DC5, sn⁺

para^B

amorphic allele - genetic evidence

ethyl methanesulfonate

y¹ w^* para^B P{neoFRT}19A/FM7c, P{GAL4-Kr.C}DC1, P{UAS-GFP.S65T}DC5, sn⁺

para^{MI08578-FlpStop.D}

amorphic allele - genetic evidence

phiC31 integrase

y¹ w^* Mi{FlpStop}para^{MI08578-FlpStop.D}/FM7c

References (17)

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