EFHD2
protein-codingEF-hand domain family member D2, the group of EF-hand domain containing
Gene summary
Enables actin filament binding activity and calcium ion sensor activity. Involved in actin crosslink formation. Is active in lamellipodium. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EFHD2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024329.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 26 | 26 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 27 | 0 | 0 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_077305.2 | 4 | MANE Select | |
| Ensembl | ENSP00000365147.4 | 4 | MANE Select | |
| Ensembl | ENSP00000395153.1 | 5 | Standard | |
| Ensembl | ENSP00000576315.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Molecular Function
- calcium ion binding
- cadherin binding
Cellular Component
- membrane raft
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000375980
- Coding exons
- 4
- Length
- 20449
- Individuals with no LoFs
- 125703
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125708
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.963 | 96 | 126 | 0.759 | 0.00000734 | 1576 |
| Missense (PolyPhen) | 33 | 50.879 | 0.6486 | 579 | ||
| Synonymous | -0.134 | 56 | 54.7 | 1.02 | 0.00000356 | 451 |
| Loss of Function | 1.09 | 4 | 7.15 | 0.560 | 3.02e-7 | 100 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000035 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.0000090 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May regulate B-cell receptor (BCR)-induced immature and primary B-cell apoptosis. Plays a role as negative regulator of the canonical NF-kappa-B-activating branch. Controls spontaneous apoptosis through the regulation of BCL2L1 abundance. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.124
Intolerance Scores
- LoFtool
- 0.414
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.194
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |