GLRX5

Chr 14AR

glutaredoxin 5

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

The encoded mitochondrial protein facilitates iron-sulfur cluster biogenesis, which is essential for normal iron homeostasis. Autosomal recessive mutations cause pyridoxine-refractory sideroblastic anemia and childhood-onset spasticity with hyperglycinemia. Pathogenicity results from disrupted iron-sulfur cluster assembly, leading to impaired cellular iron metabolism and mitochondrial dysfunction.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismARLOEUF 0.662 OMIM phenotypes
Clinical SummaryGLRX5
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.66LOEUF
pLI 0.746
Z-score 1.97
OE 0.00 (0.000.66)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
0.22Z-score
OE missense 0.93 (0.761.14)
68 obs / 73.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.66)
00.351.4
Missense OE0.93 (0.761.14)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 0 / 4.5Missense obs/exp: 68 / 73.2Syn Z: 0.04
DN
0.5378th %ile
GOF
0.6345th %ile
LOF
0.52top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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