REL

Chr 2AR

REL proto-oncogene, NF-kB subunit

Also known as: C-Rel, HIVEN86A, IMD92

The REL protein functions as a component of NF-kappa-B transcription factor complexes that regulate genes involved in immunity, inflammation, differentiation, and apoptosis, with particular importance for B lymphocyte survival and proliferation. Loss-of-function mutations cause autosomal recessive immunodeficiency 92, likely through impaired NF-kappa-B signaling critical for immune system function. The inheritance pattern is autosomal recessive with pathogenicity resulting from loss of normal protein function.

Summary from RefSeq, OMIM, UniProt, Mechanism
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Primary Disease Associations & Inheritance

Immunodeficiency 92MIM #619652
AR
1
Active trials
243
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.23
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryREL
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Gene-Disease Validity (ClinGen)
immunodeficiency 92 · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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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

LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 0.998
Z-score 4.51
OE 0.07 (0.030.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.76Z-score
OE missense 0.73 (0.660.81)
243 obs / 333.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.07 (0.030.23)
00.351.4
Missense OE0.73 (0.660.81)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 2 / 27.5Missense obs/exp: 243 / 333.2Syn Z: 0.40
DN
0.3594th %ile
GOF
0.2597th %ile
LOF
0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.23

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

REL · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
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