GULP1

Chr 2

GULP PTB domain containing engulfment adaptor 1

NCBI Gene: 51454ENSG00000144366UniProt: Q9UBP9

May function as an adapter protein. Required for efficient phagocytosis of apoptotic cells. Modulates cellular glycosphingolipid and cholesterol transport. May play a role in the internalization and endosomal trafficking of various LRP1 ligands, such as PSAP. Increases cellular levels of GTP-bound ARF6

68
ClinVar variants
26
Pathogenic / LP
0.69
pLI score
0
Active trials
Clinical Summary— GULP1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.69) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 28 VUS of 68 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.46LOEUF
pLI 0.687
Z-score 3.13
OE 0.18 (0.08–0.46)
Moderately constrained

More LoF-intolerant than ~75% 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.
0.98Z-score
OE missense 0.78 (0.67–0.91)
122 obs / 156.6 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.0.18 (0.08–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.67–0.91)
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.0.88
0≤1.21.6
LoF obs/exp: 3 / 16.9Missense obs/exp: 122 / 156.6Syn Z: 0.72

ClinVar Variant Classifications

68 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic1
VUS28
Likely Benign2
Benign3
25
Pathogenic
1
Likely Pathogenic
28
VUS
2
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
0
0
1
0
1
VUS
0
25
3
0
28
Likely Benign
0
1
1
0
2
Benign
0
0
3
0
3
Total02633059

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

View in ClinVar →

Protein Context — Lollipop Plot

GULP1 · 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
GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma.
Kim HS et al.·Clin Mol Hepatol
2025
Attenuation of amyloid-β generation by atypical protein kinase C-mediated phosphorylation of engulfment adaptor PTB domain containing 1 threonine 35.
Chau DD et al.·FASEB J
2019
GULP1 regulates the NRF2-KEAP1 signaling axis in urothelial carcinoma.
Hayashi M et al.·Sci Signal
2020
GATA2 downregulation contributes to pro-inflammatory phenotype and defective phagocytosis of pulmonary macrophages in chronic obstructive pulmonary disease.
Shen S et al.·Aging (Albany NY)
2024
VAMP8 as a biomarker and potential therapeutic target for endothelial cell dysfunction in atherosclerosis.
Yang L et al.·Gene
2025
Tissue-specific gene expression of genome-wide significant loci associated with major depressive disorder subtypes.
Torii K et al.·Prog Neuropsychopharmacol Biol Psychiatry
2024
Phenome-wide association study and functional annotation of hemoglobin A1c-associated variants in African populations.
Soremekun C et al.·PLoS One
2025Functional
Clinicopathological and genetic characterization of radiotherapy-induced undifferentiated pleomorphic sarcoma following breast cancer: a case series of three tumors and comprehensive literature review.
Lei T et al.·Diagn Pathol
2024Review
Hemizygous deletion of COL3A1, COL5A2, and MSTN causes a complex phenotype with aortic dissection: a lesson for and from true haploinsufficiency.
Meienberg J et al.·Eur J Hum Genet
2010
The APC/C E3 ligase subunit ANAPC11 mediates FOXO3 protein degradation to promote cell proliferation and lymph node metastasis in urothelial bladder cancer.
Yan D et al.·Cell Death Dis
2023
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