UNC119

protein-coding

unc-119 lipid binding chaperone

Gene summary

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]

MANE transcript

NM_005148.4

Inheritance

ClinVar variants

P:1U:135B:58

Top phenotype

Immunodeficiency 13

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr17:28,546,708-28,552,631

External References & Databases

Ensembl (ENSG00000109103)

Transcript & Mutation Effects

hg38 • Region Span ~5.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cone-rod dystrophyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0015993

Submitter: G2P

idiopathic CD4 lymphocytopeniaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014226

Submitter: PanelApp Australia

cone-rod dystrophy 24MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0957240

Submitter: PanelApp Australia

cone-rod dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015993

Submitter: Orphanet

cone-rod dystrophy 24LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0957240

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Immunodeficiency 13AD

Manifestation: Allergy/Immunology/Infectious; Ophthalmologic

Intervention: Allergy/Immunology/Infectious

Rationale: 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

Refs: 11006213; 22184408; 23563732; 28005958; 35947183

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UNC119 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 208

not specifiedTotal: 42

Cone-rod dystrophyTotal: 20

UNC119-related disorderTotal: 9

Cone-rod dystrophy 24Total: 4

Idiopathic CD4 lymphocytopeniaTotal: 3

Macular dystrophyTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005148.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				50 clinvar	2 clinvar	52
missense			117 clinvar	6 clinvar		123
nonsense		1 clinvar	4 clinvar			5
start loss			1 clinvar			1
frameshift			6 clinvar			6
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	1	135	56	2	194

Highest pathogenic variant AF is 0.000004336992

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005148.4	RefSeq	NP_005139.1	5	MANE Select
ENST00000335765.9	Ensembl	ENSP00000337040.3	5	MANE Select
NM_001330166.2	RefSeq	NP_001317095.1	4	Standard
NM_054035.2	RefSeq	NP_473376.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
unc119b	Danio rerio	Structure: Kupffer's vesicle Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

unc119b

Danio rerio

Structure: Kupffer's vesicle

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Biological Process

mitotic cytokinesis
endocytosis
chemical synaptic transmission
nervous system development
visual perception

Molecular Function

protein binding
lipid binding

Cellular Component

spindle pole
centrosome
cytosol
intercellular bridge
spindle midzone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000335765
Coding exons: 5
Length: 5962
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125746
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.928	115	147	0.784	0.00000929	1557
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.192

Intolerance Scores

LoFtool: 0.346
RVIS EVS: -0.34
RVIS percentile EVS: 30.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.429

Gene Damage Prediction

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