GLRX5

Chr 14AR

glutaredoxin 5

Also known as: C14orf87, FLB4739, GRX5, PR01238, PRO1238, PRSA, SIDBA3, SPAHGC

NCBI Gene: 51218ENSG00000182512UniProt: Q86SX6

This gene encodes a mitochondrial protein, which is evolutionarily conserved. It is involved in the biogenesis of iron-sulfur clusters, which are required for normal iron homeostasis. Mutations in this gene are associated with autosomal recessive pyridoxine-refractory sideroblastic anemia. [provided by RefSeq, May 2010]

Primary Disease Associations & Inheritance

Anemia, sideroblastic, 3, pyridoxine-refractoryMIM #616860
AR
Spasticity, childhood-onset, with hyperglycinemiaMIM #616859
AR
163
ClinVar variants
30
Pathogenic / LP
0.75
pLI score
1
Active trials
Clinical Summary— GLRX5
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 67 VUS of 163 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.66LOEUF
pLI 0.746
Z-score 1.97
OE 0.00 (0.00–0.66)
Moderately constrained

Typical tolerance to LoF variation

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.
0.22Z-score
OE missense 0.93 (0.76–1.14)
68 obs / 73.2 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.0.00 (0.00–0.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.76–1.14)
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.0.99
0≤1.21.6
LoF obs/exp: 0 / 4.5Missense obs/exp: 68 / 73.2Syn Z: 0.04

ClinVar Variant Classifications

163 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic3
VUS67
Likely Benign53
Benign12
Conflicting1
27
Pathogenic
3
Likely Pathogenic
67
VUS
53
Likely Benign
12
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
5
20
1
27
Likely Pathogenic
0
1
2
0
3
VUS
3
57
7
0
67
Likely Benign
0
0
19
34
53
Benign
0
2
8
2
12
Conflicting
—1
Total4655637163

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

View in ClinVar →

Protein Context — Lollipop Plot

GLRX5 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
GLUTAREDOXIN 5; GLRX5
MIM #609588 · *

Anemia, sideroblastic, 3, pyridoxine-refractory

MIM #616860

Molecular basis of disorder known

Autosomal recessive

Spasticity, childhood-onset, with hyperglycinemia

MIM #616859

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — GLRX5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
HACE1, GLRX5, and ELP2 gene variant cause spastic paraplegies.
Sager G et al.·Acta Neurol Belg
2022
GLRX5 is a prognostic marker in bladder cancer and correlates with activation of cancer-associated fibroblasts in the tumor microenvironment.
Wang Y et al.·Exp Cell Res
2026
GLRX5-associated [Fe-S] cluster biogenesis disorder: further characterisation of the neurological phenotype and long-term outcome.
Sankaran BP et al.·Orphanet J Rare Dis
2021
Lipoic acid biosynthesis defects.
Mayr JA et al.·J Inherit Metab Dis
2014Review
Functional Analysis of GLRX5 Mutants Reveals Distinct Functionalities of GLRX5 Protein.
Liu G et al.·J Cell Biochem
2016Functional
Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5.
Baker PR 2nd et al.·Brain
2014Case report
Differential diagnosis of lipoic acid synthesis defects.
Tort F et al.·J Inherit Metab Dis
2016Review
The chimeric transcript RUNX1-GLRX5: a biomarker for good postoperative prognosis in Stage IA non-small-cell lung cancer.
Ishikawa R et al.·Jpn J Clin Oncol
2016
Salvia miltiorrhiza Bge. processed with porcine cardiac blood inhibited GLRX5-mediated ferroptosis alleviating cerebral ischemia-reperfusion injury.
Zhou S et al.·Phytomedicine
2024
Identification of four mitochondria-related genes in sepsis based on RNA sequencing technology.
ShilinLi et al.·BMC Immunol
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
AnemiaGeneticsErythropoiesis

Genomic of CONgenital Sideroblastic Anemias

RECRUITING
NCT07459816Phase NACentre Hospitalier Universitaire, AmiensStarted 2025-10-28
blood redrawal

External Resources

Links to major genomics databases and tools