RFX5

Chr 1AR

regulatory factor X5

Also known as: MHC2D3, MHC2D5

NCBI Gene: 5993ENSG00000143390UniProt: P48382

A lack of MHC-II expression results in a severe immunodeficiency syndrome called MHC-II deficiency, or the bare lymphocyte syndrome (BLS; MIM 209920). At least 4 complementation groups have been identified in B-cell lines established from patients with BLS. The molecular defects in complementation groups B, C, and D all lead to a deficiency in RFX, a nuclear protein complex that binds to the X box of MHC-II promoters. The lack of RFX binding activity in complementation group C results from mutations in the RFX5 gene encoding the 75-kD subunit of RFX (Steimle et al., 1995). RFX5 is the fifth member of the growing family of DNA-binding proteins sharing a novel and highly characteristic DNA-binding domain called the RFX motif. Multiple alternatively spliced transcript variants have been found but the full-length natures of only two have been determined. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?MHC class II deficiency 5MIM #620818
AR
MHC class II deficiency 3MIM #620816
AR
491
ClinVar variants
64
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RFX5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
64 Pathogenic / Likely Pathogenic· 253 VUS of 491 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.
1.10LOEUF
pLI 0.000
Z-score 1.14
OE 0.76 (0.53–1.10)
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.
0.48Z-score
OE missense 0.93 (0.84–1.02)
314 obs / 338.7 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.0.76 (0.53–1.10)
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 (0.84–1.02)
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.0.75
0≤1.21.6
LoF obs/exp: 20 / 26.3Missense obs/exp: 314 / 338.7Syn Z: 2.23

ClinVar Variant Classifications

491 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic22
VUS253
Likely Benign138
Benign11
Conflicting11
42
Pathogenic
22
Likely Pathogenic
253
VUS
138
Likely Benign
11
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
19
0
23
0
42
Likely Pathogenic
18
1
3
0
22
VUS
5
213
34
1
253
Likely Benign
0
6
50
82
138
Benign
0
1
6
4
11
Conflicting
—11
Total4222111687477

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

View in ClinVar →

Protein Context — Lollipop Plot

RFX5 · 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

?MHC class II deficiency 5

MIM #620818

Molecular basis of disorder known

Autosomal recessive

MHC class II deficiency 3

MIM #620816

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Metabolic checkpoints in rheumatoid arthritis.
Weyand CM et al.·Semin Arthritis Rheum
2025Review
A patient with RFX5 variant causing an expression defect in both HLA ABC and HLA DR.
Goktas S et al.·Immunol Res
2025Case report
Identification of RFX5 as prognostic biomarker and associated with immune infiltration in stomach adenocarcinoma.
Guo L et al.·Eur J Med Res
2022
MHC Class II Deficiency: Clinical, Immunological, and Genetic Insights in a Large Multicenter Cohort.
Gulec Koksal Z et al.·J Allergy Clin Immunol Pract
2024Cohort
MHC class I and II deficiencies.
Hanna S et al.·J Allergy Clin Immunol
2014Review
Interferon gamma repression of collagen (COL1A2) transcription is mediated by the RFX5 complex.
Xu Y et al.·J Biol Chem
2003
Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India.
Vignesh P et al.·Front Immunol
2021
MHC-II Deficiency Among Egyptians: Novel Mutations and Unique Phenotypes.
El Hawary RE et al.·J Allergy Clin Immunol Pract
2019Case report
Clinical, Immunological, and Genetic Findings in Iranian Patients with MHC-II Deficiency: Confirmation of c.162delG RFXANK Founder Mutation in the Iranian Population.
Mousavi Khorshidi MS et al.·J Clin Immunol
2023Cohort
Effects of baicalin on Chlamydia trachomatis infection in vitro.
Hao H et al.·Planta Med
2010
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