EEFSEC

Chr 3AR

eukaryotic elongation factor, selenocysteine-tRNA specific

Also known as: EFSEC, NEDPSB, SELB

NCBI Gene: 60678 ENSG00000132394 UniProt: P57772 OMIM: 607695

The EEFSEC protein is a translation factor that enables incorporation of selenocysteine into proteins by delivering selenocysteinyl-tRNA to ribosomes at UGA codons. Mutations cause a neurodevelopmental disorder with progressive spasticity and brain abnormalities, inherited in an autosomal recessive pattern. The gene shows low constraint against loss-of-function variants (pLI near zero), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables GTPase activity. Involved in selenocysteine incorporation. Predicted to be located in cytoplasm and nucleus. Predicted to be part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with progressive spasticity and brain abnormalitiesMIM #621102

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Neurodevelopmental disorder with progressive spasticity and brain abnormalities; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.18

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.18LOEUF

pLI 0.000

Z-score 0.98

OE 0.76 (0.50–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.63Z-score

OE missense 0.91 (0.83–0.99)

325 obs / 358.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.76 (0.50–1.18)

0≤0.351.4

Missense OE?0.91 (0.83–0.99)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 14 / 18.5Missense obs/exp: 325 / 358.8Syn Z: 0.31

Background carrier burden — how many people carry a rare variant somewhere in EEFSEC?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 56

801 rare PASS variants

Rare truncating (LoF)

1 in 1,200

106 rare PASS variants

Rare synonymous (reference)

1 in 170

369 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EEFSEC. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 76	1 in 1,100
South Asian	~43k	1 in 63	1 in 1,500
Remaining (unassigned)	~30k	1 in 58	1 in 2,300
European (Finnish)	~27k	1 in 210	1 in 3,500
Admixed American	~22k	1 in 46	1 in 3,000
African / African American	~21k	1 in 67	1 in 1,600
East Asian	~20k	1 in 68	1 in 670
Ashkenazi Jewish	~13k	1 in 170	1 in 1,300
Middle Eastern	~2,884	1 in 62	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓