HECW1

Chr 7

HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1

Also known as: NEDL1

NCBI Gene: 23072ENSG00000002746UniProt: Q76N89

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in regulation of dendrite morphogenesis and ubiquitin-dependent protein catabolic process. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

232
ClinVar variants
25
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— HECW1
⚡
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.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 199 VUS of 232 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.25LOEUF
pLI 1.000
Z-score 7.22
OE 0.16 (0.11–0.25)
Highly constrained

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

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.
2.95Z-score
OE missense 0.74 (0.69–0.78)
733 obs / 995.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.16 (0.11–0.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.69–0.78)
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.0.93
0≤1.21.6
LoF obs/exp: 14 / 86.4Missense obs/exp: 733 / 995.1Syn Z: 1.17

ClinVar Variant Classifications

232 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic1
VUS199
Likely Benign3
Benign5
24
Pathogenic
1
Likely Pathogenic
199
VUS
3
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
1
0
1
VUS
0
192
7
0
199
Likely Benign
0
2
0
1
3
Benign
0
0
2
3
5
Total0194344232

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

View in ClinVar →

Protein Context — Lollipop Plot

HECW1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
High expression of HECW1 is associated with the poor prognosis and cancer progression of gastric cancer.
Yang Z et al.·World J Surg Oncol
2025
Changes E3 ubiquitin protein ligase 1 gene mRNA expression correlated with IgA1 glycosylation in patients with IgA nephropathy.
Liu Y et al.·Ren Fail
2019Cohort
HECW1 restrains cervical cancer cell growth by promoting DVL1 ubiquitination and downregulating the activation of Wnt/β-catenin signaling.
Xu Z et al.·Exp Cell Res
2024
Integrating HECW1 expression into the clinical indicators exhibits high accuracy in assessing the prognosis of patients with clear cell renal cell carcinoma.
Wang C et al.·BMC Cancer
2021Cohort
HECW1 Gene's Role in Gastric Cancer Prognosis and Its Suppressive Effect on Cell Progression after Knockdown.
Wang J et al.·Crit Rev Eukaryot Gene Expr
2025
Alu Deletions in LAMA2 and CDH4 Genes Are Key Components of Polygenic Predictors of Longevity.
Erdman VV et al.·Int J Mol Sci
2022
Study of Ubiquitin Pathway Genes in a French Population with Amyotrophic Lateral Sclerosis: Focus on HECW1 Encoding the E3 Ligase NEDL1.
Haouari S et al.·Int J Mol Sci
2023
Estrogen degrades Scribble in endometrial epithelial cells through E3 ubiquitin ligase HECW1 in the development of diffuse adenomyosis†.
Jin Z et al.·Biol Reprod
2020
Expression and regulatory network of E3 ubiquitin ligase NEDD4 family in cancers.
Cao L et al.·BMC Cancer
2023
An epigenome-wide DNA methylation study of patients with COVID-19.
Zhou S et al.·Ann Hum Genet
2021Cohort
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