UBAP1L

protein-coding

ubiquitin associated protein 1 like

Gene summary

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. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001163692.2

Inheritance

ClinVar variants

P:7U:93B:5

Top phenotype

inherited retinal dystrophy

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr15:65,092,760-65,115,200

External References & Databases

Ensembl (ENSG00000246922)

Transcript & Mutation Effects

hg38 • Region Span ~22.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cone-rod dystrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0015993

Submitter: PanelApp Australia

inherited retinal dystrophyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019118

Submitter: Ambry Genetics

inherited retinal dystrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0019118

Submitter: LiferaOmics

Genetic evidence – Published PMID: 39325468 – Family 1 – one proband. Case-level (AR homozygous; predicted null; loss-of-function mechanism plausible; consanguineous family; −0.5 consanguinity deduction applied) = 1.0; Segregation = 0; Case-control = 0 Family 1 total = 1.0 PMID: 39325468 – Family 2 – one proband. Case-level (AR homozygous; predicted null; loss-of-function mechanism plausible; consanguineous family; −0.5 consanguinity deduction applied) = 1.0; Segregation = 0; Case-control = 0 Family 2 total = 1.0 PMID: 39325468 – Family 3 – one proband. Case-level (AR homozygous; predicted null; loss-of-function mechanism plausible; no consanguinity deduction applied [not reported]) = 1.5; Segregation = 0; Case-control = 0 Family 3 total = 1.5 PMID: 39325468 – Family 4 – one proband. Case-level (AR homozygous; predicted null; loss-of-function mechanism plausible; no consanguinity deduction applied [not reported]) = 1.5; Segregation = 0; Case-control = 0 Family 4 total = 1.5 PMID: 39325468 – Family 5 – one proband. Case-level (AR homozygous; predicted null; loss-of-function mechanism plausible; no consanguinity deduction applied [non-consanguineous]) = 1.5; Segregation = 0; Case-control = 0 Family 5 total = 1.5 PMID: 39325468 – Family 6 – one proband. Case-level (AR homozygous; predicted null; loss-of-function mechanism plausible; no consanguinity deduction applied [non-consanguineous]) = 1.5; Segregation = 0; Case-control = 0 Family 6 total = 1.5 Subtotal (PMID 39325468) = 8.0 PMID: 38293907 – Family 7 – one proband. Case-level (AR homozygous; predicted null; loss-of-function mechanism plausible; consanguineous family; −0.5 consanguinity deduction applied) = 1.0; Segregation = 0; Case-control = 0 Family 7 total = 1.0 PMID: 38293907 – Family 8 – one proband. Case-level (AR homozygous; predicted null; loss-of-function mechanism plausible; consanguineous family; −0.5 consanguinity deduction applied) = 1.0; Segregation = 0; Case-control = 0 Family 8 total = 1.0 PMID: 38293907 – Family 9 – one proband. Case-level (AR homozygous; predicted null; loss-of-function mechanism plausible; consanguineous family; −0.5 consanguinity deduction applied) = 1.0; Segregation = 0; Case-control = 0 Family 9 total = 1.0 PMID: 38293907 – Family 10 – one proband. Case-level (AR homozygous; predicted null; loss-of-function mechanism plausible; consanguineous family; −0.5 consanguinity deduction applied) = 1.0; Segregation = 0; Case-control = 0 Family 10 total = 1.0 Subtotal (PMID 38293907) = 4.0 Published genetic evidence total = 12.0 / 12 Genetic evidence – Our case Family 1 – one proband. Case-level (AR homozygous; predicted null p.Arg287Ter; loss-of-function mechanism plausible; consanguineous family; −0.5 consanguinity deduction applied) = 1.0; Segregation = 0; Case-control = 0 Family 1 total = 1.0 Our case total = 1.0 / 12 Total genetic evidence (published AR + our case) 12.0 (published AR; cap reached) + 1.0 (our case) = 12.0 / 12 (cap maintained) Experimental evidence – Published (conservative) PMID: 39325468 – Functional alteration (retinal expression + minigene splice assay). Demonstrated UBAP1L expression in cones and RPE; minigene assay confirmed aberrant splicing leading to frameshift. Functional alteration (engineered system; conservative) = 0.5 PMID: 39325468 – Function (retinal relevance). Single-cell RNA sequencing demonstrated retinal cell-type expression supporting biological plausibility. Function (retinal expression relevance; conservative) = 0.5 Experimental evidence total = 1.0 / 6 Overall score Genetic evidence = 12.0 Experimental evidence = 1.0 Overall score = 13.0 / 18

retinal degenerationMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0004580

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UBAP1L variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 96

RETINAL DYSTROPHY, ZEITZ-HAN TYPETotal: 5

Retinal dystrophyTotal: 4

not providedTotal: 3

Tooth agenesis, selective, 7Total: 1

UBAP1L-related disorderTotal: 1

Isolated macular dystrophyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001163692.2. 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				1 clinvar	1 clinvar	2
missense	2 clinvar		93 clinvar	3 clinvar		98
nonsense	1 clinvar					1
start loss						0
frameshift	2 clinvar					2
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar				2
Total	6	1	93	4	1	105

Highest pathogenic variant AF is 0.000116137126

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001163692.2	RefSeq	NP_001157164.1	5	MANE Select
ENST00000559089.6	Ensembl	ENSP00000454012.1	5	MANE Select
ENST00000558802.1	Ensembl	ENSP00000452794.1	3	Standard
ENST00000907325.1	Ensembl	ENSP00000577384.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway

Molecular Function

ubiquitin binding

Cellular Component

ESCRT I complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000559089
Coding exons: 5
Length: 22198
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.740	128	154	0.832	0.00000934	2388
Missense (PolyPhen)		43	57.11	0.75293		893
Synonymous	0.870	60	69.2	0.867	0.00000453	848
Loss of Function	1.50	5	10.2	0.492	5.19e-7	140

Population LoF Frequency

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

dbNSFP Gene Annotations

Source: dbNSFP

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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