LYRM4

Chr 6AR

LYR motif containing 4

Also known as: C6orf149, CGI-203, COXPD19, ISD11

NCBI Gene: 57128ENSG00000214113UniProt: Q9HD34

The protein encoded by this gene is found in both mitochondria and the nucleus, where it binds cysteine desulfurase and helps free inorganic sulfur for Fe/S clusters. Disruption of this gene negatively impacts mitochondrial and cytosolic iron homeostasis. [provided by RefSeq, Sep 2016]

Primary Disease Associations & Inheritance

?Combined oxidative phosphorylation deficiency 19MIM #615595
AR
267
ClinVar variants
53
Pathogenic / LP
0.20
pLI score
0
Active trials
Clinical Summary— LYRM4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.20) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
53 Pathogenic / Likely Pathogenic· 159 VUS of 267 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.54LOEUF
pLI 0.200
Z-score 0.98
OE 0.36 (0.13–1.54)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.36Z-score
OE missense 0.86 (0.67–1.10)
43 obs / 50.2 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.0.36 (0.13–1.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.67–1.10)
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.0.78
0≤1.21.6
LoF obs/exp: 1 / 2.8Missense obs/exp: 43 / 50.2Syn Z: 0.74

ClinVar Variant Classifications

267 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic48
Likely Pathogenic5
VUS159
Likely Benign25
Benign30
48
Pathogenic
5
Likely Pathogenic
159
VUS
25
Likely Benign
30
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
47
0
48
Likely Pathogenic
0
0
5
0
5
VUS
1
129
28
1
159
Likely Benign
0
4
17
4
25
Benign
0
1
29
0
30
Total11351265267

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

View in ClinVar →

Protein Context — Lollipop Plot

LYRM4 · 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

?Combined oxidative phosphorylation deficiency 19

MIM #615595

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic Regulation of Alternative Polyadenylation Provides Novel Insights into Molecular Mechanisms Underlying Non-small Cell Lung Cancer.
Jin M et al.·Adv Sci (Weinh)
2025Functional
Mitochondrial-related genome-wide Mendelian randomization identifies putatively causal genes in the pathogenesis of sepsis.
Sun J et al.·Surgery
2025Review
High LYRM4-AS1 predicts poor prognosis in patients with glioma and correlates with immune infiltration.
Wang HY et al.·PeerJ
2023Cohort
Mutations in LYRM4, encoding iron-sulfur cluster biogenesis factor ISD11, cause deficiency of multiple respiratory chain complexes.
Lim SC et al.·Hum Mol Genet
2013
A Cuproptosis-Related lncRNA Signature Predicts Prognosis and Shapes the Immune Landscape in Primary Lower-Grade Glioma.
Wang M et al.·Genet Res (Camb)
2025
Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship.
Anderson CA et al.·Gastroenterology
2009
6p25 interstitial deletion in two dizygotic twins with gyral pattern anomaly and speech and language disorder.
Bozza M et al.·Eur J Paediatr Neurol
2013Review
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools