UBAP1L

Summary

UBAP1L (ubiquitin associated protein 1 like, HGNC:40028) is a protein-coding gene on chromosome 15q22.31, encoding Ubiquitin-associated protein 1-like (F5GYI3).

Predicted to enable ubiquitin binding activity. Predicted to be involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Predicted to be part of ESCRT I complex.

Source: NCBI Gene 390595 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited retinal dystrophy (Definitive, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 106 total — 6 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 15
• MANE Select transcript: NM_001163692

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:40028
Approved symbol	UBAP1L
Name	ubiquitin associated protein 1 like
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000246922
Ensembl biotype	protein_coding
Entrez	390595

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000558802, ENST00000559089, ENST00000561387, ENST00000907325

RefSeq mRNA: 1 — MANE Select: NM_001163692 NM_001163692

CCDS: CCDS53948

Canonical transcript exons

ENST00000559089 — 6 exons

Exon	Start	End
ENSE00002203620	65102106	65102684
ENSE00002227020	65094475	65094576
ENSE00002290505	65099505	65099714
ENSE00002543149	65115150	65115200
ENSE00002546161	65092760	65093231
ENSE00002558286	65106096	65106388

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 91.10.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2999 / max 120.1740, expressed in 30 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150522	0.2471	24
150523	0.0425	9
150521	0.0103	3

Top tissues by expression

245 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	91.10	gold quality
cerebellar hemisphere	UBERON:0002245	90.66	gold quality
cerebellar cortex	UBERON:0002129	90.57	gold quality
pigmented layer of retina	UBERON:0001782	89.84	gold quality
cerebellum	UBERON:0002037	89.28	gold quality
right frontal lobe	UBERON:0002810	83.85	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.57	gold quality
hypothalamus	UBERON:0001898	80.49	gold quality
anterior cingulate cortex	UBERON:0009835	80.37	gold quality
spinal cord	UBERON:0002240	79.27	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.22	gold quality
right ovary	UBERON:0002118	77.85	gold quality
nucleus accumbens	UBERON:0001882	77.72	gold quality
left ovary	UBERON:0002119	77.71	gold quality
putamen	UBERON:0001874	77.33	gold quality
endocervix	UBERON:0000458	77.03	gold quality
amygdala	UBERON:0001876	76.94	gold quality
caudate nucleus	UBERON:0001873	76.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.29	gold quality
right lobe of liver	UBERON:0001114	76.28	gold quality
neocortex	UBERON:0001950	76.25	gold quality
body of uterus	UBERON:0009853	76.25	gold quality
brain	UBERON:0000955	76.24	gold quality
lower esophagus mucosa	UBERON:0035834	76.08	gold quality
frontal cortex	UBERON:0001870	75.62	gold quality
granulocyte	CL:0000094	75.47	gold quality
ectocervix	UBERON:0012249	75.43	gold quality
primary visual cortex	UBERON:0002436	75.36	gold quality
prefrontal cortex	UBERON:0000451	75.34	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7249	no	14.59
E-ANND-3	no	4.35

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Variants in UBAP1L lead to autosomal recessive rod-cone and cone-rod dystrophy. (PMID:38293907)
• Loss-of-function variants in UBAP1L cause autosomal recessive retinal degeneration. (PMID:38420906)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubap1la	ENSDARG00000089217
mus_musculus	Ubap1l	ENSMUSG00000086228
rattus_norvegicus	Ubap1l	ENSRNOG00000050979
drosophila_melanogaster	CG10435	FBGN0037539

Paralogs (1): UBAP1 (ENSG00000165006)

Protein

Protein identifiers

Ubiquitin-associated protein 1-like — F5GYI3 (reviewed: F5GYI3)

All UniProt accessions (2): F5GYI3, H0YKG2

RefSeq proteins (1): NP_001157164* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR023340	UMA	Domain
IPR038870	UBAP1	Family
IPR042575	UBAP1_C	Homologous_superfamily
IPR049467	UBAP-1-like_UBA2	Domain

Pfam: PF21267

UniProt features (9 total): compositionally biased region 4, region of interest 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-F5GYI3-F1	66.48	0.29

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS_VIA_THE_MULTIVESICULAR_BODY_SORTING_PATHWAY, GOBP_PROTEIN_CATABOLIC_PROCESS, GOCC_ESCRT_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOBP_PROTEOLYSIS, GOMF_UBIQUITIN_LIKE_PROTEIN_BINDING, chr15q22, GOCC_ESCRT_I_COMPLEX, GOMF_UBIQUITIN_BINDING, GOCC_ENDOSOME_MEMBRANE, HMG20B_TARGET_GENES, HMGA1_TARGET_GENES, PHF21A_TARGET_GENES, BLANCO_MELO_MERS_COV_INFECTION_MCR5_CELLS_UP

GO Biological Process (1): ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway (GO:0043162)

GO Molecular Function (1): ubiquitin binding (GO:0043130)

GO Cellular Component (1): ESCRT I complex (GO:0000813)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ubiquitin-dependent protein catabolic process	1
protein catabolic process in the vacuole	1
multivesicular body sorting pathway	1
ubiquitin-like protein binding	1
endosome membrane	1
ESCRT complex	1
membrane protein complex	1

Protein interactions and networks

STRING

164 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBAP1L	TVP23C	Q96ET8	479
UBAP1L	A0A0A6YYB9	A0A0A6YYB9	477
UBAP1L	ROPN1L	Q96C74	356
UBAP1L	PARM1	Q6UWI2	311
UBAP1L	PDZD7	Q9H5P4	298
UBAP1L	TSPAN13	O95857	297
UBAP1L	COL19A1	Q14993	288
UBAP1L	PDGFRL	Q15198	287
UBAP1L	LARS2	Q15031	277
UBAP1L	INKA2	Q9NTI7	263
UBAP1L	SEPTIN5	Q99719	257
UBAP1L	ATP1B2	P14415	255
UBAP1L	CA14	Q9ULX7	248
UBAP1L	SLC4A10	Q6U841	248
UBAP1L	SLC66A2	Q8N2U9	232

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A0U1RQ45, A0A1B0GWB2, A2A9T0, A6QPA0, A7MCY6, D3ZFB6, E9PUL5, E9Q0B3, F5GYI3, F5H4A9, J3QNX5, O70142, P0C1G7, P81408, P97764, P98077, Q148V8, Q15654, Q2KI80, Q3SX26, Q3SZL6, Q4V9L6, Q5FVJ4, Q5FW56, Q5RAC1, Q5T7N3, Q6DG50, Q6PAJ3, Q6PJ61, Q6ZMQ8, Q6ZNR0, Q6ZRV2, Q75VX8, Q7Z6L0, Q86UK7, Q86VE0, Q8BGW2, Q8BRJ3, Q8BX43, Q8C0R7

Diamond homologs: F5GYI3, Q5XIS7, Q8BH48, Q9NZ09, F6P6X0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

106 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	1
Uncertain significance	91
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
3341497	NM_001163692.2(UBAP1L):c.121-2A>C	Pathogenic
3341498	NM_001163692.2(UBAP1L):c.634_644del (p.Ser212fs)	Pathogenic
3341499	NM_001163692.2(UBAP1L):c.710del (p.Pro237fs)	Pathogenic
4819947	R287*	Pathogenic
4819949	NM_001163692.2(UBAP1L):c.278C>A (p.Thr93Lys)	Pathogenic
4819950	NM_001163692.2(UBAP1L):c.1051A>G (p.Met351Val)	Pathogenic
3336852	NM_001163692.2(UBAP1L):c.120+1G>T	Likely pathogenic

SpliceAI

1430 predictions. Top by Δscore:

Variant	Effect	Δscore
15:65093228:CTGC:C	acceptor_gain	1.0000
15:65093231:CCTGA:C	acceptor_loss	1.0000
15:65093232:C:CA	acceptor_loss	1.0000
15:65093233:T:C	acceptor_loss	1.0000
15:65094583:C:CT	acceptor_gain	1.0000
15:65093229:TGC:T	acceptor_gain	0.9900
15:65093232:C:CC	acceptor_gain	0.9900
15:65094470:CTGA:C	donor_loss	0.9900
15:65094471:TGA:T	donor_loss	0.9900
15:65094472:GACC:G	donor_loss	0.9900
15:65094473:A:T	donor_loss	0.9900
15:65094577:C:CC	acceptor_gain	0.9900
15:65094583:C:T	acceptor_gain	0.9900
15:65094584:G:T	acceptor_gain	0.9900
15:65094589:C:CT	acceptor_gain	0.9900
15:65094590:G:T	acceptor_gain	0.9900
15:65098988:A:AC	donor_gain	0.9900
15:65098989:C:CC	donor_gain	0.9900
15:65098989:CATT:C	donor_gain	0.9900
15:65099715:C:CC	acceptor_gain	0.9900
15:65102680:TCGTG:T	acceptor_gain	0.9900
15:65102681:CGTG:C	acceptor_gain	0.9900
15:65102681:CGTGC:C	acceptor_gain	0.9900
15:65102683:TGC:T	acceptor_loss	0.9900
15:65102684:GCT:G	acceptor_loss	0.9900
15:65102685:C:CA	acceptor_loss	0.9900
15:65102685:C:CC	acceptor_gain	0.9900
15:65115145:CTTA:C	donor_loss	0.9900
15:65115146:TTA:T	donor_loss	0.9900
15:65115147:TA:T	donor_loss	0.9900

AlphaMissense

2429 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:65093185:A:G	F353S	0.998
15:65093184:G:C	F353L	0.997
15:65093184:G:T	F353L	0.997
15:65093186:A:G	F353L	0.997
15:65094493:G:C	F331L	0.997
15:65094493:G:T	F331L	0.997
15:65094495:A:G	F331L	0.997
15:65093200:A:G	F348S	0.996
15:65093220:G:C	F341L	0.996
15:65093220:G:T	F341L	0.996
15:65093222:A:G	F341L	0.996
15:65093158:A:G	L362P	0.994
15:65093221:A:G	F341S	0.994
15:65093116:A:G	L376P	0.992
15:65093158:A:T	L362Q	0.992
15:65093166:C:A	K359N	0.992
15:65093166:C:G	K359N	0.992
15:65093199:G:C	F348L	0.992
15:65093199:G:T	F348L	0.992
15:65093201:A:G	F348L	0.992
15:65094495:A:T	F331I	0.992
15:65094507:C:G	A327P	0.991
15:65099536:A:G	L293P	0.991
15:65093185:A:C	F353C	0.990
15:65093218:A:G	L342P	0.989
15:65094545:A:G	L314P	0.989
15:65094494:A:G	F331S	0.988
15:65094563:A:G	L308P	0.988
15:65099590:A:G	L275P	0.988
15:65093212:A:G	L344P	0.986

dbSNP variants (sampled 300 via entrez): RS1000293240 (15:65094060 T>G), RS1000494837 (15:65111191 G>A), RS1000840880 (15:65110818 A>T), RS1000881712 (15:65112921 A>C,T), RS1000983869 (15:65092340 C>G,T), RS1001155036 (15:65102205 CG>C), RS1001203459 (15:65098127 G>A), RS1001238209 (15:65094764 C>T), RS1001257377 (15:65101297 A>C), RS1001386914 (15:65105310 C>G), RS1001431811 (15:65107654 G>A,C), RS1001447159 (15:65112400 G>A), RS1001896750 (15:65112788 G>A,T), RS1002020738 (15:65093973 G>A), RS1002213237 (15:65100161 T>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:616724

GenCC curated gene-disease

Disease	Classification	Inheritance
inherited retinal dystrophy	Definitive	Autosomal recessive
cone-rod dystrophy	Strong	Autosomal recessive
retinal degeneration	Moderate	Autosomal recessive

Mondo (5): isolated macular dystrophy (MONDO:0957048), inherited retinal dystrophy (MONDO:0019118), tooth agenesis, selective, 7 (MONDO:0014749), retinal degeneration (MONDO:0004580), cone-rod dystrophy (MONDO:0015993)

Orphanet (3): OBSOLETE: Isolated macular dystrophy (Orphanet:519302), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Oligodontia (Orphanet:99798)

HPO phenotypes

15 total (16 of 15 shown, HPO-id order):

HPO	Term
HP:0000505	Visual impairment
HP:0000529	Progressive visual loss
HP:0000543	Optic disc pallor
HP:0000551	Color vision defect
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0001105	Retinal atrophy
HP:0007641	Dyschromatopsia
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007843	Attenuation of retinal blood vessels
HP:0012508	Metamorphopsia
HP:0030466	Abnormal full-field electroretinogram
HP:0000556	Retinal dystrophy

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D012162	Retinal Degeneration	C11.270.612; C11.768.585
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	3
clothianidin	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Melphalan	increases expression	1
Quercetin	increases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-3-isobutylxanthine	decreases expression, affects cotreatment	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

108 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00716586	PHASE4	COMPLETED	Treatment of Cystoid Macular Edema in Patients With Retinal Degeneration
NCT02157077	PHASE3	COMPLETED	Aflibercept After Ranibizumab in Exudative Age-related Macular Degeneration
NCT03954626	PHASE3	COMPLETED	Study to Collect Safety and ECG Data on Brolucizumab 6 mg Intravitreal Treatment in Patients With Wet AMD
NCT06305416	PHASE3	RECRUITING	A Efficacy and Safety Study of Ranibizumab 10mg/ml Injection (Incepta) in Patients With Diabetic Macular Edema
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT02348359	PHASE2	TERMINATED	X-82 to Treat Age-related Macular Degeneration
NCT04643886	PHASE2	TERMINATED	A Multiple Dose Study of Repeat Intravitreal Injections of GEM103 in Dry Age-related Macular Degeneration
NCT04684394	PHASE2	TERMINATED	A Multiple Dose Study of Repeat Intravitreal Injections of GEM103 in Neovascular Age-related Macular Degeneration
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT06011798	PHASE2	COMPLETED	Assess the Efficacy and Safety of Repeat Intravitreal Injections of Foselutoclax (UBX1325) in Patients With DME (ASPIRE)
NCT07174687	PHASE2	RECRUITING	SGLT2 Inhibitors in Geographic Atrophy
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT00877032	PHASE1	COMPLETED	Safety And Tolerability Study Of RN6G In Patients With Dry, Age-Related Macular Degeneration
NCT01003691	PHASE1	COMPLETED	Safety And Tolerability Study Of RN6G In Subjects With Advanced Dry, Age-Related Macular Degeneration Including Geographic Atrophy
NCT01024998	PHASE1	COMPLETED	Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD)
NCT02330978	PHASE1	COMPLETED	Intravitreal Mesenchymal Stem Cell Transplantation in Advanced Glaucoma.
NCT02543229	PHASE1	COMPLETED	Study Evaluating the Safety, Pharmacokinetics and Pharmacodynamics of OPT-302 With or Without Lucentis™ in Patients With Wet AMD
NCT03772938	PHASE1	UNKNOWN	Stem Cells Therapy in Degenerative Diseases of the Retina
NCT04246866	PHASE1	COMPLETED	First in Human Study to Evaluate the Safety and Tolerability of GEM103 in Geographic Atrophy Secondary to Dry Age Related Macular Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT00643747	PHASE1/PHASE2	COMPLETED	Safety Study of RPE65 Gene Therapy to Treat Leber Congenital Amaurosis
NCT01278277	PHASE1/PHASE2	UNKNOWN	Saffron Supplementation in Stargardt’s Disease
NCT01494805	PHASE1/PHASE2	COMPLETED	Safety and Efficacy Study of rAAV.sFlt-1 in Patients With Exudative Age-Related Macular Degeneration
NCT02144103	PHASE1/PHASE2	UNKNOWN	Effectiveness and Safety of Adipose-Derived Regenerative Cells for Treatment of Glaucomatous Neurodegeneration
NCT03846193	PHASE1/PHASE2	TERMINATED	FOCUS: A Phase I/II First in Human Study to Evaluate the Safety and Efficacy of GT005 Administered in Subjects With Dry AMD
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT04919473	PHASE1/PHASE2	COMPLETED	Dose-Escalation Study to Evaluate the Safety and Tolerability of Intravitreal vMCO-I in Patients With Advanced Retinitis Pigmentosa
NCT05474729	PHASE1/PHASE2	RECRUITING	Minocycline for Chronic Autoimmune Uveitis
NCT06789445	PHASE1/PHASE2	RECRUITING	A Study to Investigate the Safety of OpCT-001 in Adults Who Have Primary Photoreceptor Disease (CLARICO)
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT03078309	EARLY_PHASE1	UNKNOWN	The Effects of Cannabis on Visual Functions in Healthy and Retinitis Pigmentosa Patients
NCT06289452	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study of IVB102 Injection in Subjects With X-linked Retinoschisis