UBXN4

protein-coding

UBX domain protein 4, the group of UBX domain containing

Gene summary

UBXD2 is an integral membrane protein of the endoplasmic reticulum (ER) that binds valosin-containing protein (VCP; MIM 601023) and promotes ER-associated protein degradation (ERAD) (Liang et al., 2006 [PubMed 16968747]).[supplied by OMIM, Mar 2008]

Previous symbols:

UBXDC1
UBXD2

MANE transcript

NM_014607.4

Inheritance

—

ClinVar variants

U:81B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr2:135,741,734-135,785,056

External References & Databases

Ensembl (ENSG00000144224)

Transcript & Mutation Effects

hg38 • Region Span ~43.3 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 UBXN4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 70

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014607.4. 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			4 clinvar			4
missense			71 clinvar	3 clinvar		74
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	81	3	0	84

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014607.4	RefSeq	NP_055422.1	13	MANE Select
ENST00000272638.14	Ensembl	ENSP00000272638.9	13	MANE Select
ENST00000415164.5	Ensembl	ENSP00000401748.1	5	Standard
ENST00000416538.5	Ensembl	ENSP00000391586.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ubxn4	Danio rerio	Structure: melanophore stripe Quality: disorganized abnormal

Gene / Model

Organism

Observed Phenotype

ubxn4

Danio rerio

Structure: melanophore stripe

Quality: disorganized

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

response to unfolded protein
ubiquitin-dependent ERAD pathway

Molecular Function

protein binding

Cellular Component

nuclear envelope
endoplasmic reticulum
endoplasmic reticulum membrane
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000272638
Coding exons: 13
Length: 43437
Individuals with no LoFs: 124771
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 124794
p: 0.0000922

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.46	193	259	0.745	0.0000128	3308
Missense (PolyPhen)		25	50.506	0.49499		643
Synonymous	-0.0173	91	90.8	1.00	0.00000478	953
Loss of Function	3.64	7	27.7	0.253	0.00000139	361

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00020	0.00017	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000098	0.000097	rare
South Asian	0.00014	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in endoplasmic reticulum-associated protein degradation (ERAD). Acts as a platform to recruit both UBQLN1 and VCP to the ER during ERAD (PubMed:19822669). {ECO:0000269|PubMed:16968747, ECO:0000269|PubMed:19822669}.;

Recessive Scores

pRec: 0.104

Intolerance Scores

LoFtool: 0.344
RVIS EVS: -0.14
RVIS percentile EVS: 43.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.940

Gene Damage Prediction

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