EFL1

Chr 15AR

elongation factor like GTPase 1

Also known as: EFTUD1, FAM42A, HsT19294, RIA1, SDS2

NCBI Gene: 79631 ENSG00000140598 UniProt: Q7Z2Z2 OMIM: 617538

EFL1 encodes a GTPase that triggers the release of EIF6 from 60S pre-ribosomes in the cytoplasm, enabling ribosome activation for translation competence and facilitating ribosome assembly. Mutations cause Shwachman-Diamond syndrome, which follows autosomal recessive inheritance and typically presents with exocrine pancreatic dysfunction, bone marrow failure, and skeletal abnormalities. The gene is highly constrained against loss-of-function variants (LOEUF 0.561), reflecting its essential role in ribosome biogenesis.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

Enables GTPase activity and ribosome binding activity. Involved in GTP metabolic process and cytosolic ribosome assembly. Predicted to be part of ribonucleoprotein complex. Predicted to be active in cytosol. Implicated in Shwachman-Diamond syndrome. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.561 OMIM phenotype

Clinical Summary— EFL1

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Gene-Disease Validity (ClinGen)

Shwachman-Diamond syndrome 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

6 unique Pathogenic / Likely Pathogenic· 279 VUS of 588 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — EFL1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.000

Z-score 4.27

OE 0.40 (0.28–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.25Z-score

OE missense 0.86 (0.80–0.92)

507 obs / 592.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.28–0.56)

0≤0.351.4

Missense OE?0.86 (0.80–0.92)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 23 / 58.1Missense obs/exp: 507 / 592.7Syn Z: 0.26

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongEFL1-related Shwachman-Diamond syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6745th %ile

GOF

0.5856th %ile

LOF

0.3068th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

588 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic4

VUS279

Likely Benign259

Benign17

Conflicting7

Pathogenic

Likely Pathogenic

279

VUS

259

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	1	0	0	2
Likely Pathogenic	2	2	0	0	4
VUS	14	247	17	1	279
Likely Benign	0	12	92	155	259
Benign	0	4	6	7	17
Conflicting	—				7
Total	17	266	115	163	568

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap EFL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →