RHBDD1

Chr 2

rhomboid domain containing 1

Also known as: RHBDL4, RRP4

NCBI Gene: 84236ENSG00000144468UniProt: Q8TEB9

Enables serine-type endopeptidase activity. Involved in several processes, including cellular response to unfolded protein; membrane protein proteolysis; and positive regulation of protein catabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

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0
Active trials
4
Pubs (1 yr)
0
P/LP submissions
—
P/LP missense
1.71
LOEUF
DN
Mechanism· predicted
Clinical Summary— RHBDD1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.71LOEUF
pLI 0.000
Z-score -0.58
OE 1.16 (0.79–1.71)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.02Z-score
OE missense 1.00 (0.88–1.13)
171 obs / 171.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.16 (0.79–1.71)
0≤0.351.4
Missense OE1.00 (0.88–1.13)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 17 / 14.6Missense obs/exp: 171 / 171.8Syn Z: -0.49
DN
0.81top 10%
GOF
0.6346th %ile
LOF
0.2288th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

RHBDD1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
RHBDD1 silencing inhibited cell growth and invasion of non-small cell lung cancer by mediating ZEB1/PI3K/AKT signaling pathway.
Xu Z et al.·J Mol Histol
2021
Rhomboid domain containing 1 promotes the growth of non-small cell lung cancer through the activation of EGFR and regulation of the BIK-mediated apoptosis.
Xu ZY et al.·Neoplasma
2022
Prognostic and Immunological Significance of Rhomboid Domain Containing Protein 1 in Multiple Primary Cancers.
Wang T et al.·Comb Chem High Throughput Screen
2022
Suppression of rhomboid domain-containing 1 produces anticancer effects in pancreatic adenocarcinoma through affection of the AKT/GSK-3beta/beta-catenin pathway.
Jiang J et al.·Environ Toxicol
2022
RHBDD1 promotes proliferation, migration, invasion and EMT in renal cell carcinoma via the EGFR/AKT signaling pathway
Li M et al.·Mol Med Rep
2021
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients