TULP1

Chr 6AR

TUB like protein 1

NCBI Gene: 7287ENSG00000112041UniProt: O00294

Required for normal development of photoreceptor synapses. Required for normal photoreceptor function and for long-term survival of photoreceptor cells. Interacts with cytoskeleton proteins and may play a role in protein transport in photoreceptor cells (By similarity). Binds lipids, especially phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-bisphosphate, phosphatidylserine and phosphatidic acid (in vitro). Contribute to stimulation of phagocytosis of apoptotic retinal pigment epithelium (RPE) cells and macrophages

Primary Disease Associations & Inheritance

Leber congenital amaurosis 15MIM #613843
AR
Retinitis pigmentosa 14MIM #600132
AR
596
ClinVar variants
104
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TULP1
🧬
Gene-Disease Validity (ClinGen)
Leber congenital amaurosis 15 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
104 Pathogenic / Likely Pathogenic· 170 VUS of 596 total submissions

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.
0.60LOEUF
pLI 0.001
Z-score 3.22
OE 0.37 (0.23–0.60)
Tolerant

Typical tolerance to LoF variation

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.
0.65Z-score
OE missense 0.90 (0.82–0.99)
295 obs / 328.0 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.0.37 (0.23–0.60)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.82–0.99)
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.0.91
0≤1.21.6
LoF obs/exp: 11 / 30.1Missense obs/exp: 295 / 328.0Syn Z: 0.86

ClinVar Variant Classifications

596 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic54
VUS170
Likely Benign286
Benign7
Conflicting29
50
Pathogenic
54
Likely Pathogenic
170
VUS
286
Likely Benign
7
Benign
29
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
28
4
18
0
50
Likely Pathogenic
22
22
10
0
54
VUS
3
146
19
2
170
Likely Benign
1
1
134
150
286
Benign
0
1
6
0
7
Conflicting
—29
Total54174187152596

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

View in ClinVar →

Protein Context — Lollipop Plot

TULP1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TULP1-related retinitis pigmentosa

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Leber congenital amaurosis 15

MIM #613843

Molecular basis of disorder known

Autosomal recessive

Retinitis pigmentosa 14

MIM #600132

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — TULP1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Comprehensive Molecular Screening in Chinese Usher Syndrome Patients.
Sun T et al.·Invest Ophthalmol Vis Sci
2018Cohort
Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes.
Georgiou M et al.·Prog Retin Eye Res
2024Review
Natural history and biomarkers of retinal dystrophy caused by the biallelic TULP1 variant c.148delG.
Majander A et al.·Acta Ophthalmol
2023Meta-analysis
Genetic and Clinical Profile of Retinopathies Due to Disease-Causing Variants in Leber Congenital Amaurosis (LCA)-Associated Genes in a Large German Cohort.
Zobor D et al.·Int J Mol Sci
2023Cohort
Clinical and genetic studies for a cohort of patients with Leber congenital amaurosis.
Zhou Y et al.·Graefes Arch Clin Exp Ophthalmol
2024Cohort
Tulp1 deficiency causes early-onset retinal degeneration through affecting ciliogenesis and activating ferroptosis in zebrafish.
Jia D et al.·Cell Death Dis
2022Functional
Biallelic Variants in TULP1 Are Associated with Heterogeneous Phenotypes of Retinal Dystrophy.
Bodenbender JP et al.·Int J Mol Sci
2023
Novel compound heterozygous TULP1 mutations in a family with severe early-onset retinitis pigmentosa.
den Hollander AI et al.·Arch Ophthalmol
2007
Host genetic variants influencing the clinical course of hepatitis C virus infection.
Matsuura K et al.·J Med Virol
2016Review
Phenotypic and Genetic Heterogeneity of a Pakistani Cohort of 15 Consanguineous Families Segregating Variants in Leber Congenital Amaurosis-Associated Genes.
Akhtar Z et al.·Genes (Basel)
2024Cohort
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