GULP1

Chr 2

GULP PTB domain containing engulfment adaptor 1

Also known as: CED-6, CED6, GULP

NCBI Gene: 51454 ENSG00000144366 UniProt: Q9UBP9 OMIM: 608165

GULP1 encodes an adapter protein required for efficient phagocytosis of apoptotic cells and modulates cellular glycosphingolipid and cholesterol transport. The gene shows high constraint against loss-of-function variants (LOEUF 0.459), suggesting mutations would likely cause significant clinical effects, but no specific Mendelian disease has been definitively associated with GULP1 variants to date. Based on the constraint metrics, any pathogenic variants would likely follow an autosomal dominant inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is an adapter protein necessary for the engulfment of apoptotic cells by phagocytes. Several transcript variants, some protein coding and some thought not to be protein coding, have been found for this gene. [provided by RefSeq, Nov 2011]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.46

Clinical Summary— GULP1

⚡

Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.69) — some intolerance to loss-of-function variants.

📋

ClinVar Variants

26 VUS of 36 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.98Z-score

OE missense 0.78 (0.67–0.91)

122 obs / 156.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.18 (0.08–0.46)

0≤0.351.4

Missense OE?0.78 (0.67–0.91)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 3 / 16.9Missense obs/exp: 122 / 156.6Syn Z: 0.72

This gene — mechanism propensity

0.6453th %ile

GOF

0.4677th %ile

LOF

0.52top 25%

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

36 submitted variants in ClinVar

ClinVar

Classification Summary

VUS26

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	26	26
Likely Benign	1	1
Benign	0	0
Total	27	27

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap GULP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →