HEBP2

Chr 6

heme binding protein 2

Also known as: C6ORF34B, C6orf34, PP23, SOUL

NCBI Gene: 23593ENSG00000051620UniProt: Q9Y5Z4

The protein encoded by this gene is found predominately in the cytoplasm, where it plays a role in the collapse of mitochondrial membrane potential (MMP) prior to necrotic cell death. The encoded protein enhances outer and inner mitochondrial membrane permeabilization, especially under conditions of oxidative stress. [provided by RefSeq, May 2016]

47
ClinVar variants
12
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HEBP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 34 VUS of 47 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 0.000
Z-score 0.45
OE 0.83 (0.47–1.54)
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.
0.11Z-score
OE missense 0.97 (0.82–1.15)
95 obs / 98.1 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.0.83 (0.47–1.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.82–1.15)
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.0.98
0≤1.21.6
LoF obs/exp: 7 / 8.4Missense obs/exp: 95 / 98.1Syn Z: 0.12

ClinVar Variant Classifications

47 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
VUS34
Likely Benign1
12
Pathogenic
34
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
0
0
0
VUS
0
31
3
0
34
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total03215047

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

View in ClinVar →

Protein Context — Lollipop Plot

HEBP2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
HEBP2-governed glutamine competition between tumor and macrophages dictates immunotherapy efficacy in triple-negative breast cancer.
Xiao Y et al.·Cell Metab
2025
Deregulated ALG-2/HEBP2 axis alters microtubule dynamics and mitotic spindle behavior to stimulate cancer development.
Qin J et al.·J Cell Physiol
2017
Structural and Functional Study of Apoptosis-linked Gene-2·Heme-binding Protein 2 Interactions in HIV-1 Production.
Ma J et al.·J Biol Chem
2016Functional
EBP2 plays a key role in Epstein-Barr virus mitotic segregation and is regulated by aurora family kinases.
Kapoor P et al.·Mol Cell Biol
2005
Comprehensive bioinformatics analyses reveal immune genes responsible for altered immune microenvironment in intervertebral disc degeneration.
Hai B et al.·Mol Genet Genomics
2022
Methylome-wide association study of antidepressant use in Generation Scotland and the Netherlands Twin Register implicates the innate immune system.
Barbu MC et al.·Mol Psychiatry
2022Meta-analysis
Reconstitution of Epstein-Barr virus-based plasmid partitioning in budding yeast.
Kapoor P et al.·EMBO J
2001
Integrative genomics analysis identifies five promising genes implicated in insomnia risk based on multiple omics datasets.
Sun H et al.·Biosci Rep
2020
Single-cell RNA sequencing reveals changes in glioma-associated macrophage polarization and cellular states of malignant gliomas with high AQP4 expression.
Wang R et al.·Cancer Gene Ther
2023
Possible Predictive Markers of Response to Therapy in Esophageal Squamous Cell Cancer.
Zoltan L et al.·Pathol Oncol Res
2019
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