EFCAB13

Chr 17

EF-hand calcium binding domain 13

Also known as: C17orf57

NCBI Gene: 124989ENSG00000178852UniProt: Q8IY85
0
Active trials
8
Pathogenic / LP
149
ClinVar variants
2
Pubs (1 yr)
1.0
Missense Z
1.37
LOEUF
Clinical Summary— EFCAB13
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 104 VUS of 149 total submissions

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.
1.37LOEUF
pLI 0.000
Z-score -0.42
OE 1.07 (0.84–1.37)
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.
1.00Z-score
OE missense 0.87 (0.80–0.94)
412 obs / 473.3 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.1.07 (0.84–1.37)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.80–0.94)
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.0.83
0≤1.21.6
LoF obs/exp: 46 / 43.0Missense obs/exp: 412 / 473.3Syn Z: 1.67
DN
0.74top 25%
GOF
0.80top 10%
LOF
0.3065th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

149 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS104
Likely Benign17
Benign20
7
Pathogenic
1
Likely Pathogenic
104
VUS
17
Likely Benign
20
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
0
102
2
0
104
Likely Benign
1
10
2
4
17
Benign
3
6
4
7
20
Total41181611149

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

View in ClinVar →

Protein Context — Lollipop Plot

EFCAB13 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Contribution of Rare and Low-Frequency Variants to Multiple Sclerosis Susceptibility in the Italian Continental Population
Clarelli F et al.·Front Genet
2022
PSRC1 May Affect Coronary Artery Disease Risk by Altering CELSR2, PSRC1, and SORT1 Gene Expression and Circulating Granulin and Apolipoprotein B Protein Levels
Chai T et al.·Front Cardiovasc Med
2022
Genetic risk variants for multiple sclerosis are linked to differences in alternative pre-mRNA splicing
Putscher E et al.·Front Immunol
2022
Genetic Overlap Between Obstructive Sleep Apnea and Ischemic Stroke: A Large-Scale Genome-Wide Cross-Trait Analysis
Lin W et al.·Nat Sci Sleep
2025
Deep sequencing of 1320 genes reveals the landscape of protein-truncating variants and their contribution to psoriasis in 19,973 Chinese individuals
Xu H et al.·Genome Res
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients