EFHC1

Chr 6AD

EF-hand domain containing 1

Also known as: EJM1, POC9, RIB72, dJ304B14.2

NCBI Gene: 114327ENSG00000096093UniProt: Q5JVL4

This gene encodes an EF-hand-containing calcium binding protein. The encoded protein likely plays a role in calcium homeostasis. Mutations in this gene have been associated with susceptibility to juvenile myoclonic epilepsy and juvenile absence epilepsy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

Primary Disease Associations & Inheritance

{Epilepsy, juvenile absence, susceptibility to, 1}MIM #607631
AD
{Myoclonic epilepsy, juvenile, susceptibility to, 1}MIM #254770
AD
UniProtJuvenile myoclonic epilepsy 1
UniProtJuvenile absence epilepsy 1
466
ClinVar variants
12
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EFHC1
🧬
Gene-Disease Validity (ClinGen)
epilepsy · ADRefuted

Refuted — evidence has disproved this relationship

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 277 VUS of 466 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.21LOEUF
pLI 0.000
Z-score 0.63
OE 0.88 (0.65–1.21)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.14Z-score
OE missense 0.98 (0.90–1.07)
350 obs / 357.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.88 (0.65–1.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.90–1.07)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 28 / 31.8Missense obs/exp: 350 / 357.5Syn Z: 0.46

ClinVar Variant Classifications

466 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic2
VUS277
Likely Benign119
Benign32
Conflicting26
10
Pathogenic
2
Likely Pathogenic
277
VUS
119
Likely Benign
32
Benign
26
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
9
0
10
Likely Pathogenic
0
0
2
0
2
VUS
12
227
32
6
277
Likely Benign
1
16
43
59
119
Benign
0
2
27
3
32
Conflicting
—26
Total1424511368466

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EFHC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Epilepsy, juvenile absence, susceptibility to, 1}

MIM #607631

Molecular basis of disorder known

Autosomal dominant

{Myoclonic epilepsy, juvenile, susceptibility to, 1}

MIM #254770

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — EFHC1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Pathogenic EFHC1 mutations are tolerated in healthy individuals dependent on reported ancestry.
Subaran RL et al.·Epilepsia
2015
Microtubule-associated defects caused by EFHC1 mutations in juvenile myoclonic epilepsy.
Raju PK et al.·Hum Mutat
2017
EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality.
Bailey JN et al.·Genet Med
2017
EFHC1 gene mutation profile of Turkish JME patients and its association with disease risk.
Aslan-Kara K et al.·Seizure
2024Cohort
Revisiting the clinical impact of variants in EFHC1 in patients with different phenotypes of genetic generalized epilepsy.
Gonsales MC et al.·Epilepsy Behav
2020Cohort
Seizures of idiopathic generalized epilepsies.
Durón RM et al.·Epilepsia
2005Review
Mutational analysis of EFHC1 gene in Italian families with juvenile myoclonic epilepsy.
Annesi F et al.·Epilepsia
2007
Clinical application of trio-based whole-exome sequencing in idiopathic generalized epilepsy.
Lin ZJ et al.·Seizure
2024
Predictive value of EFHC1 variants for the long-term seizure outcome in juvenile myoclonic epilepsy.
von Podewils F et al.·Epilepsy Behav
2015
Mutational Analysis of Myoclonin1 Gene in Pakistani Juvenile Myoclonic Epilepsy Patients.
Saleem T et al.·Biomed Res Int
2021Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools