UBQLN4

protein-coding

ubiquilin 4, the group of Ubiquilin family

Gene summary

Enables K48-linked polyubiquitin modification-dependent protein binding activity and identical protein binding activity. Involved in several processes, including negative regulation of autophagosome maturation; negative regulation of double-strand break repair via homologous recombination; and regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in several cellular components, including autophagosome; proteasome complex; and site of DNA damage. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C1orf6

MANE transcript

NM_020131.5

Inheritance

—

ClinVar variants

P:1U:60B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr1:156,035,299-156,053,798

External References & Databases

Ensembl (ENSG00000160803)

Transcript & Mutation Effects

hg38 • Region Span ~18.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UBQLN4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 59

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020131.5. 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				3 clinvar	1 clinvar	4
missense			58 clinvar	1 clinvar	1 clinvar	60
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	0	60	4	2	67

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020131.5	RefSeq	NP_064516.2	11	MANE Select
ENST00000368309.4	Ensembl	ENSP00000357292.3	11	MANE Select
NM_001304342.2	RefSeq	NP_001291271.1	11	Standard
ENST00000879792.1	Ensembl	ENSP00000549851.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein processing in endoplasmic reticulum - Homo sapiens (human)

Biological Process

autophagy
regulation of proteasomal ubiquitin-dependent protein catabolic process
negative regulation of autophagosome maturation

Molecular Function

protein binding
polyubiquitin modification-dependent protein binding
identical protein binding

Cellular Component

nucleus
cytoplasm
autophagosome
endoplasmic reticulum membrane
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368309
Coding exons: 11
Length: 18494
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125744
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.88	196	347	0.565	0.0000198	3894
Missense (PolyPhen)		45	100.07	0.44969		1090
Synonymous	1.33	119	139	0.857	0.00000836	1249
Loss of Function	4.13	3	25.6	0.117	0.00000124	269

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	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000027	0.000018	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the regulation of protein degradation via the ubiquitin-proteasome system (UPS). Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding (via UBA domain) to their polyubiquitin chains and by interacting (via ubiquitin-like domain) with the subunits of the proteasome (Ref. 6). Plays a role in the regulation of the proteasomal degradation of non-ubiquitinated GJA1 (By similarity). Acts as an adapter protein that recruits UBQLN1 to the autophagy machinery. Mediates the association of UBQLN1 with autophagosomes and the autophagy-related protein LC3 (MAP1LC3A/B/C) and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome-lysosome fusion (PubMed:23459205). {ECO:0000250|UniProtKB:Q99NB8, ECO:0000269|PubMed:15280365, ECO:0000269|PubMed:23459205}.;

Recessive Scores

pRec: 0.134

Intolerance Scores

LoFtool: 0.174
RVIS EVS: 0.06
RVIS percentile EVS: 58.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.766

Gene Damage Prediction

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