UNC119

Chr 17AD

unc-119 lipid binding chaperone

Also known as: CORD24, HRG4, IMD13, POC7, POC7A

NCBI Gene: 9094UniProt: Q13432

This gene is specifically expressed in the photoreceptors in the retina. The encoded product shares strong homology with the C. elegans unc119 protein and it can functionally complement the C. elegans unc119 mutation. It has been localized to the photoreceptor synapses in the outer plexiform layer of the retina, and suggested to play a role in the mechanism of photoreceptor neurotransmitter release through the synaptic vesicle cycle. Two transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Immunodeficiency 13MIM #615518
AD
Cone-rod dystrophy 24MIM #620342
AD
254
ClinVar variants
7
Pathogenic / LP
0.00
pLI score
0.9
Missense Z
1.33
LOEUF
0
Active trials
Clinical Summary— UNC119
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 152 VUS of 254 total submissions
Some data sources returned errors (1)

ensembl: Error: Ensembl fetch failed: 500 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/UNC119?content-type=application/json&expand=1

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.
1.33LOEUF
pLI 0.000
Z-score 0.85
OE 0.71 (0.40–1.33)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.93Z-score
OE missense 0.78 (0.67–0.92)
115 obs / 146.6 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.0.71 (0.40–1.33)
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 (0.67–0.92)
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.1.00
0≤1.21.6
LoF obs/exp: 7 / 9.9Missense obs/exp: 115 / 146.6Syn Z: 0.01

ClinVar Variant Classifications

254 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic2
VUS152
Likely Benign75
Benign12
Conflicting8
5
Pathogenic
2
Likely Pathogenic
152
VUS
75
Likely Benign
12
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
2
0
2
VUS
9
121
20
2
152
Likely Benign
0
4
24
47
75
Benign
0
0
10
2
12
Conflicting
—8
Total91256151254

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

View in ClinVar →

Protein Context — Lollipop Plot

UNC119 · protein map & ClinVar variants

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

Gene2Phenotype Curations

UNC119-related cone-rod dystrophy

limited
ADUndeterminedUncertain
Eye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Immunodeficiency 13

MIM #615518

Molecular basis of disorder known

Autosomal dominant

Cone-rod dystrophy 24

MIM #620342

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Consequences of a mutation in the UNC119 gene for T cell function in idiopathic CD4 lymphopenia.
Gorska MM et al.·Curr Allergy Asthma Rep
2012Review
UNC119 promotes the growth and migration of hepatocellular carcinoma via Wnt/β-catenin and TGF-β/EMT signaling pathways.
Liu Z et al.·J BUON
2018
UNC119 promotes the growth and migration of hepatocellular carcinoma via Wnt/β/catenin and TGF/β-EMT signaling pathways.
Liu Z et al.·J BUON
2018
UNC119 promoted cell growth and migration by Wnt/β-catenin signal and TGF-β/EMT signal pathway in hepatocellular carcinoma.
Liu ZH et al.·J BUON
2018
Curcumin Modulates Hepatocellular Carcinoma by Reducing UNC119 Expression.
Zhao Z et al.·J Environ Pathol Toxicol Oncol
2019
C9orf72 FTLD/ALS-associated Gly-Ala dipeptide repeat proteins cause neuronal toxicity and Unc119 sequestration.
May S et al.·Acta Neuropathol
2014
Clinical-genetic findings in a group of subjects with macular dystrophies due to mutations in rare inherited retinopathy genes.
Zenteno JC et al.·Graefes Arch Clin Exp Ophthalmol
2023
HRG4 (UNC119) mutation found in cone-rod dystrophy causes retinal degeneration in a transgenic model.
Kobayashi A et al.·Invest Ophthalmol Vis Sci
2000Functional
Mapping of a novel type III variant of Knobloch syndrome (KNO3) to chromosome 17q11.2.
Khaliq S et al.·Am J Med Genet A
2007
Whole-Exome Sequencing Detecting a Recurrent Pathogenic Mutation, HFE p.His63Asp (H63D) in COVID-19 Patients and Its Effect on Mortality.
Mir R et al.·Discov Med
2024Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients