HBEGF

Chr 5

heparin binding EGF like growth factor

Also known as: DTR, DTS, DTSF, HEGFL

The protein functions as a growth factor that binds to and activates EGFR, ERBB2, and ERBB4 receptors, and is required for normal cardiac valve formation and heart function. Mutations cause increased susceptibility to diphtheria through a dominant-negative mechanism, as the protein also serves as the cellular receptor for diphtheria toxin. The condition follows an autosomal dominant inheritance pattern.

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

{Diphtheria, susceptibility to}
1
Active trials
40
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.94
LOEUF
DN
Mechanism· predicted
Clinical SummaryHBEGF
Population Constraint (gnomAD)
Low constraint (pLI 0.08) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.076
Z-score 1.69
OE 0.36 (0.170.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.36Z-score
OE missense 0.65 (0.540.78)
77 obs / 118.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.170.94)
00.351.4
Missense OE0.65 (0.540.78)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 3 / 8.2Missense obs/exp: 77 / 118.9Syn Z: -0.15
DN
0.74top 25%
GOF
0.5562th %ile
LOF
0.3648th %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

Protein Context — Lollipop Plot

HBEGF · 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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