EFCAB14

Chr 1

EF-hand calcium binding domain 14

Also known as: KIAA0494

NCBI Gene: 9813 ENSG00000159658 UniProt: O75071 OMIM: 619559

The EFCAB14 protein is predicted to bind calcium ions and localize to cellular membranes. Mutations in this gene have not been definitively associated with human disease based on the available information. This gene appears to tolerate loss-of-function variants well, as indicated by its low constraint scores.

OMIM ResearchSummary from RefSeq

Predicted to enable calcium ion binding activity. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.95

Clinical Summary— EFCAB14

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

64 VUS of 86 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.73

OE 0.62 (0.41–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.39Z-score

OE missense 0.93 (0.84–1.03)

247 obs / 265.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.41–0.95)

0≤0.351.4

Missense OE?0.93 (0.84–1.03)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 15 / 24.2Missense obs/exp: 247 / 265.1Syn Z: -0.51

This gene — mechanism propensity

0.76top 25%

GOF

0.5563th %ile

LOF

0.2680th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

86 submitted variants in ClinVar

ClinVar

Classification Summary

VUS64

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	64	64
Likely Benign	2	2
Benign	0	0
Total	66	66

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap EFCAB14 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →