MACIR

Chr 5

macrophage immunometabolism regulator

Also known as: C5orf30

NCBI Gene: 90355ENSG00000181751UniProt: Q96GV9

This gene, MACIR (previously known as C5orf30), has been associated with rheumatoid arthritis, functioning as a negative regulator of tissue damage and modulating the activity of synovial fibroblasts and macrophages. The encoded protein is highly conserved in vertebrate genomes but has no significant similarity to any other human protein. [provided by RefSeq, Dec 2019]

34
ClinVar variants
21
Pathogenic / LP
0.43
pLI score
0
Active trials
Clinical Summary— MACIR
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.19) despite low pLI — interpret in context.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 10 VUS of 34 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.
0.89LOEUF
pLI 0.427
Z-score 1.74
OE 0.19 (0.07–0.89)
Tolerant

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.
1.16Z-score
OE missense 0.71 (0.59–0.84)
86 obs / 122.0 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.0.19 (0.07–0.89)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.59–0.84)
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.1.17
0≤1.21.6
LoF obs/exp: 1 / 5.3Missense obs/exp: 86 / 122.0Syn Z: -0.93

ClinVar Variant Classifications

34 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic2
VUS10
Likely Benign3
19
Pathogenic
2
Likely Pathogenic
10
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————19
Likely Pathogenic
————2
VUS
————10
Likely Benign
————3
Benign
————0
Total—34

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MACIR · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Resolving the Interactome of the Human Macrophage Immunometabolism Regulator (MACIR) with Enhanced Membrane Protein Preparation and Affinity Proteomics.
McGauran G et al.·Proteomics
2020
Human macrophage immunometabolism regulator (MACIR) in patients with periodontitis.
Serwin K et al.·Immunobiology
2023Cohort
C5orf30 is a negative regulator of tissue damage in rheumatoid arthritis.
Muthana M et al.·Proc Natl Acad Sci U S A
2015
The Autoimmune Susceptibility Gene C5orf30 Regulates Macrophage-Mediated Resolution of Inflammation.
Dorris ER et al.·J Immunol
2019
Allele-dose association of the C5orf30 rs26232 variant with joint damage in rheumatoid arthritis.
Teare MD et al.·Arthritis Rheum
2013Meta-analysis
Association of the Rheumatoid Arthritis Severity Variant rs26232 with the Invasive Activity of Synovial Fibroblasts.
Dorris ER et al.·Cells
2019
Rheumatoid arthritis: C5orf30 regulates severity of tissue destruction in RA.
Onuora S·Nat Rev Rheumatol
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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