GLRX5

Chr 14

glutaredoxin 5

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

NCBI Gene: 51218 ENSG00000182512 UniProt: Q86SX6

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.66

Clinical Summary— GLRX5

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.

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ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 63 VUS of 141 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 — GLRX5

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.22Z-score

OE missense 0.93 (0.76–1.14)

68 obs / 73.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.66)

0≤0.351.4

Missense OE?0.93 (0.76–1.14)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 0 / 4.5Missense obs/exp: 68 / 73.2Syn Z: 0.04

This gene — mechanism propensity

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

141 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic2

VUS63

Likely Benign53

Benign12

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	5	0	1	7
Likely Pathogenic	0	2	0	0	2
VUS	2	59	2	0	63
Likely Benign	0	0	19	34	53
Benign	0	2	8	2	12
Conflicting	—				2
Total	3	68	29	37	139

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap GLRX5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →