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…

Primary Disease Associations & Inheritance

Shwachman-Diamond syndrome 2MIM #617941

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Shwachman-Diamond syndrome 2 · AR · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.56

LOEUF

LOF

Mechanism· G2P

📖

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

Background carrier burden — how many people carry a rare variant somewhere in EFL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

1,212 rare PASS variants

Rare truncating (LoF)

1 in 1,200

145 rare PASS variants

Rare synonymous (reference)

1 in 140

436 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EFL1. 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 71	1 in 1,200
South Asian	~43k	1 in 48	1 in 3,100
Remaining (unassigned)	~30k	1 in 48	1 in 1,700
European (Finnish)	~27k	1 in 150	1 in 760
Admixed American	~22k	1 in 51	1 in 2,300
African / African American	~21k	1 in 40	1 in 920
East Asian	~20k	1 in 54	1 in 790
Ashkenazi Jewish	~13k	1 in 220	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 53	≈ 1 in 1,400

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): 17 of 19 coding exons well covered in gnomAD exomes; exons 4, 15 marginal. Genomes: all 19.? see exons ↓