UNC119

unc-119 lipid binding chaperone

Basic information

Region (hg38): 17:28546708-28552631

Links

ENSG00000109103 ∙ NCBI:9094 ∙ OMIM:604011 ∙ HGNC:12565 ∙ Uniprot:Q13432 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cone-rod dystrophy (Supportive), mode of inheritance: AD
• cone-rod dystrophy 24 (Limited), mode of inheritance: Unknown
• cone-rod dystrophy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 13	AD	Allergy/Immunology/Infectious	In Immunodeficiency 13, the described invidiual suffered from frequent and severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious; Ophthalmologic	11006213; 22184408; 23563732; 28005958; 35947183

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UNC119 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UNC119 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	41	3	46
missense			100	4		104
nonsense			2			2
start loss			1			1
frameshift			5			5
inframe indel			2			2
splice donor/acceptor (+/-2bp)			3			3
splice region			1	6		7
non coding			11	16	9	36
Total	0	0	126	61	12

Variants in UNC119

This is a list of pathogenic ClinVar variants found in the UNC119 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-28546912-A-G		Cone-rod dystrophy	Likely benign (Jan 13, 2018)
17-28546919-C-T		Cone-rod dystrophy	Uncertain significance (Jan 13, 2018)
17-28546935-G-C		Cone-rod dystrophy	Benign (Jan 12, 2018)
17-28547010-A-C		Cone-rod dystrophy	Uncertain significance (Jan 13, 2018)
17-28547032-C-T		Cone-rod dystrophy	Uncertain significance (Jan 12, 2018)
17-28547071-G-A		Cone-rod dystrophy	Benign (Jan 12, 2018)
17-28547116-C-T		Cone-rod dystrophy	Uncertain significance (Jan 13, 2018)
17-28547157-T-C		Cone-rod dystrophy	Benign (Jan 13, 2018)
17-28547182-C-T		Cone-rod dystrophy	Uncertain significance (Jan 12, 2018)
17-28547214-C-G		Cone-rod dystrophy	Benign (Jan 12, 2018)
17-28547219-G-A		Cone-rod dystrophy	Uncertain significance (Jan 12, 2018)
17-28547225-G-A		Cone-rod dystrophy	Benign (Jan 13, 2018)
17-28547290-C-T		Cone-rod dystrophy	Likely benign (Jan 13, 2018)
17-28547296-G-A		not specified • Cone-rod dystrophy • Idiopathic CD4 lymphocytopenia	Benign (May 28, 2019)
17-28547299-A-G		Cone-rod dystrophy 24	Uncertain significance (Apr 04, 2024)
17-28547302-G-A			Uncertain significance (May 31, 2022)
17-28547306-C-T			Likely benign (May 18, 2018)
17-28547307-C-T			Uncertain significance (Dec 26, 2022)
17-28547308-C-T			Uncertain significance (Dec 10, 2023)
17-28547309-G-A			Likely benign (Jul 25, 2022)
17-28547309-G-C			Uncertain significance (Sep 01, 2022)
17-28547325-G-A			Uncertain significance (Nov 22, 2022)
17-28547326-C-T			Uncertain significance (Oct 21, 2024)
17-28547331-T-C		Cone-rod dystrophy	Uncertain significance (Jan 13, 2018)
17-28547340-A-C			Uncertain significance (Dec 24, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UNC119	protein_coding	protein_coding	ENST00000335765	5	5962

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000148	0.677	125733	0	13	125746	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.928	115	147	0.784	0.00000929	1557
Missense in Polyphen		52	63.099	0.82411		652
Synonymous	0.00662	58	58.1	0.999	0.00000346	462
Loss of Function	0.850	7	9.89	0.708	5.22e-7	111

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000297	0.000297
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in synaptic functions in photoreceptor cells, the signal transduction in immune cells as a Src family kinase activator, endosome recycling, the uptake of bacteria and endocytosis, protein trafficking in sensory neurons and as lipid- binding chaperone with specificity for a diverse subset of myristoylated proteins. Specifically binds the myristoyl moiety of a subset of N-terminally myristoylated proteins and is required for their localization. Binds myristoylated GNAT1 and is required for G-protein localization and trafficking in sensory neurons. Probably plays a role in trafficking proteins in photoreceptor cells. Plays important roles in mediating Src family kinase signals for the completion of cytokinesis via RAB11A. {ECO:0000269|PubMed:12496276, ECO:0000269|PubMed:14757743, ECO:0000269|PubMed:19381274, ECO:0000269|PubMed:21642972, ECO:0000269|PubMed:22085962, ECO:0000269|PubMed:23535298, ECO:0000305|PubMed:22960633}.
• Disease: DISEASE: Note=Defects in UNC119 may be a cause of cone-rod dystrophy. A mutation was found in a 57-year-old woman with late- onset cone-rod dystrophy: from 40 year old, the patient suffered from poor night vision, defective color vision and light- sensitivity. At 57 year old, she displayed reduced visual acuity, myopa, macular atrophy and pericentral ring scotomas. The disease was caused by a heterozygous mutation causing premature termination and truncated UNC119 protein with dominant-negative effect. {ECO:0000269|PubMed:11006213}.; DISEASE: Immunodeficiency 13 (IMD13) [MIM:615518]: A rare and heterogeneous syndrome defined by a reproducible reduction in the CD4 T-lymphocyte count (less than 300 cells per microliter or less than 20% of total T-cells) in the absence of HIV infection or other known causes of immunodeficiency. IMD13 predisposes to infections and malignancy. {ECO:0000269|PubMed:22184408}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: TCR;IL5 (Consensus)

Recessive Scores

• pRec: 0.192

Intolerance Scores

• loftool: 0.346
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.511
• hipred: Y
• hipred_score: 0.672
• ghis: 0.577

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.429

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Unc119
• Phenotype: liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype

Zebrafish Information Network

• Gene name: unc119b
• Affected structure: Kupffer's vesicle
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: mitotic cytokinesis;endocytosis;chemical synaptic transmission;nervous system development;visual perception;phototransduction;lipoprotein transport;positive regulation of protein tyrosine kinase activity;negative regulation of clathrin-dependent endocytosis;negative regulation of caveolin-mediated endocytosis
• Cellular component: spindle pole;centrosome;cytosol;intercellular bridge;spindle midzone
• Molecular function: protein binding;lipid binding