EFHC1

EF-hand domain containing 1, the group of EF-hand domain containing

Basic information

Region (hg38): 6:52362123-52529886

Previous symbols: [ "EJM1", "EJM" ]

Links

ENSG00000096093 ∙ NCBI:114327 ∙ OMIM:608815 ∙ HGNC:16406 ∙ Uniprot:Q5JVL4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• juvenile myoclonic epilepsy (Limited), mode of inheritance: AD
• epilepsy (Refuted Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, myoclonic juvenile; Epilepsy, juvenile absence, susceptibility to, 1	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	7668263; 12439895; 15258581; 17159113; 18505993; 19147686; 22690745; 22727576; 22926142
As with other forms of epilepsy, optimal seizure control is advantageous, and genetic diagnosis may aid with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EFHC1 gene.

• Myoclonic_epilepsy,_juvenile,_susceptibility_to,_1 (295 variants)
• Absence_seizure (270 variants)
• not_specified (124 variants)
• not_provided (89 variants)
• Juvenile_myoclonic_epilepsy (36 variants)
• Typical_absence_seizure (25 variants)
• EFHC1-related_disorder (13 variants)
• Epilepsy,_juvenile_absence,_susceptibility_to,_1 (3 variants)
• Seizure (1 variants)
• Epilepsy,_idiopathic_generalized,_susceptibility_to,_7 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EFHC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018100.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	64	3	74
missense			226	30	1	257
nonsense		1	16			17
start loss			1			1
frameshift	1		12	1		14
splice donor/acceptor (+/-2bp)			4	1		5
Total	1	1	266	96	4

Highest pathogenic variant AF is 0.000051424202

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EFHC1	protein_coding	protein_coding	ENST00000371068	11	102787

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.90e-17	0.0257	125616	0	132	125748	0.000525

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.141	350	357	0.979	0.0000213	4221
Missense in Polyphen		93	101.88	0.91287		1192
Synonymous	0.456	122	129	0.949	0.00000738	1207
Loss of Function	0.632	28	31.8	0.879	0.00000198	367

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000957	0.000957
Ashkenazi Jewish	0.000893	0.000893
East Asian	0.000761	0.000761
Finnish	0.000462	0.000462
European (Non-Finnish)	0.000520	0.000510
Middle Eastern	0.000761	0.000761
South Asian	0.000490	0.000490
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Microtubule-associated protein which regulates cell division and neuronal migration during cortical development. Necessary for mitotic spindle organization (PubMed:19734894, PubMed:28370826). Necessary for radial and tangential cell migration during brain development, possibly acting as a regulator of cell morphology and process formation during migration (PubMed:22926142). May enhance calcium influx through CACNA1E and stimulate programmed cell death (PubMed:15258581). {ECO:0000269|PubMed:15258581, ECO:0000269|PubMed:19734894, ECO:0000269|PubMed:22926142, ECO:0000269|PubMed:28370826}.
• Disease: DISEASE: Juvenile absence epilepsy 1 (JAE1) [MIM:607631]: A subtype of idiopathic generalized epilepsy characterized by onset occurring around puberty, absence seizures, generalized tonic- clonic seizures (GTCS), GTCS on awakening, and myoclonic seizures. {ECO:0000269|PubMed:17159113, ECO:0000305|PubMed:17159113}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Note=Mutation Leu-229 may be a cause of intractable epilepsy of infancy. Affected individuals have seizures of multiple type, manifested as tonic, clonic, and myoclonic seizures in the neonatal period, and as tonic seizures activated frequently by sleep, and repeated frequent myoclonic seizures in later infancy. The seizures are unresponsive to numerous antiepileptic drugs, and infants die in the first years of life. Although heterozygosity for Leu-229 has been associated with relatively benign forms of epilepsy in adolescence, homozygosity for the same mutation has much more severe consequences. {ECO:0000269|PubMed:22690745}.

Recessive Scores

• pRec: 0.155

Intolerance Scores

• loftool: 0.993
• rvis_EVS: 1.27
• rvis_percentile_EVS: 93.63

Haploinsufficiency Scores

• pHI: 0.359
• hipred: N
• hipred_score: 0.253
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.865

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Efhc1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; muscle phenotype

Gene ontology

• Biological process: mitotic cytokinesis;mitotic spindle organization;cerebral cortex cell migration;regulation of cell division
• Cellular component: spindle pole;centrosome;axoneme;neuronal cell body;mitotic spindle
• Molecular function: calcium ion binding;protein binding;protein C-terminus binding;alpha-tubulin binding