UBXN8

Summary

UBXN8 (UBX domain protein 8, HGNC:30307) is a protein-coding gene on chromosome 8p12, encoding UBX domain-containing protein 8 (O00124). Involved in endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins, possibly by tethering VCP to the endoplasmic reticulum membrane.

p97 or VCP (valosin-containing protein) is a versatile ATPase complex, and many cofactors are required for the p97 functional diversity. This gene encodes one of the p97 cofactors. This cofactor is a transmembrane protein and localized in the endoplasmic reticulum (ER) membrane. It tethers p97 to the ER membrane via its UBX domain. The association of this cofactor with p97 facilitates efficient ER-associated degradation of misfolded proteins. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7993 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_005671

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30307
Approved symbol	UBXN8
Name	UBX domain protein 8
Location	8p12
Locus type	gene with protein product
Status	Approved
Aliases	D8S2298E, REP8
Ensembl gene	ENSG00000104691
Ensembl biotype	protein_coding
OMIM	602155
Entrez	7993

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 16 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000265616, ENST00000341403, ENST00000380154, ENST00000518059, ENST00000522968, ENST00000613013, ENST00000615729, ENST00000616306, ENST00000620074, ENST00000620706, ENST00000909941, ENST00000909942, ENST00000909943, ENST00000909944, ENST00000909945, ENST00000909946, ENST00000909947, ENST00000909948, ENST00000925633, ENST00000925634, ENST00000942126

RefSeq mRNA: 3 — MANE Select: NM_005671 NM_001282189, NM_001282199, NM_005671

CCDS: CCDS75723, CCDS75724, CCDS75725

Canonical transcript exons

ENST00000265616 — 8 exons

Exon	Start	End
ENSE00001271792	30763273	30763347
ENSE00001557450	30744164	30744277
ENSE00003458228	30753035	30753105
ENSE00003552426	30760888	30760929
ENSE00003716737	30756765	30756887
ENSE00003723699	30766227	30767006
ENSE00003736234	30754665	30754787
ENSE00003790903	30751396	30751518

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 95.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.8661 / max 114.9794, expressed in 1779 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88325	11.2493	1766
88327	1.0142	633
88326	0.6026	333

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	95.09	gold quality
right ovary	UBERON:0002118	93.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.55	gold quality
ovary	UBERON:0000992	92.44	gold quality
right testis	UBERON:0004534	91.73	gold quality
left testis	UBERON:0004533	91.51	gold quality
adrenal tissue	UBERON:0018303	90.91	gold quality
testis	UBERON:0000473	89.54	gold quality
right lobe of liver	UBERON:0001114	88.36	gold quality
sural nerve	UBERON:0015488	88.28	gold quality
right adrenal gland	UBERON:0001233	87.29	gold quality
right adrenal gland cortex	UBERON:0035827	86.89	gold quality
left adrenal gland	UBERON:0001234	86.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.61	gold quality
left adrenal gland cortex	UBERON:0035825	86.46	gold quality
adrenal gland	UBERON:0002369	85.73	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.87	gold quality
adrenal cortex	UBERON:0001235	84.71	gold quality
stromal cell of endometrium	CL:0002255	84.69	gold quality
body of pancreas	UBERON:0001150	84.41	gold quality
liver	UBERON:0002107	83.82	gold quality
rectum	UBERON:0001052	83.44	gold quality
calcaneal tendon	UBERON:0003701	83.36	gold quality
left uterine tube	UBERON:0001303	82.64	gold quality
right lobe of thyroid gland	UBERON:0001119	82.52	gold quality
left lobe of thyroid gland	UBERON:0001120	82.52	gold quality
body of stomach	UBERON:0001161	82.48	gold quality
metanephros cortex	UBERON:0010533	82.32	gold quality
pancreas	UBERON:0001264	82.13	gold quality
spleen	UBERON:0002106	82.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-111727	yes	234.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting UBXN8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-150-3P	99.43	70.51	920
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-1911-5P	98.92	67.53	325
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-1910-3P	98.44	67.51	1695

Literature-anchored findings (GeneRIF, showing 1)

• Epigenetic silencing of UBXN8 contributes to leukemogenesis in t(8;21) acute myeloid leukemia. (PMID:34921223)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubxn8	ENSDARG00000098902
mus_musculus	Ubxn8	ENSMUSG00000052906
rattus_norvegicus	Ubxn8	ENSRNOG00000091028
drosophila_melanogaster	Faf2	FBGN0025608
caenorhabditis_elegans		WBGENE00010433

Paralogs (4): FAF2 (ENSG00000113194), UBXN10 (ENSG00000162543), UBXN7 (ENSG00000163960), FAF1 (ENSG00000185104)

Protein

Protein identifiers

UBX domain-containing protein 8 — O00124 (reviewed: O00124)

Alternative names: Reproduction 8 protein, UBX domain-containing protein 6

All UniProt accessions (7): A0A087WT23, A0A087WUA4, A0A087WV67, A0A087WWA4, A0A087WZN0, A0A087X0J2, O00124

UniProt curated annotations — full annotation on UniProt →

Function. Involved in endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins, possibly by tethering VCP to the endoplasmic reticulum membrane. May play a role in reproduction.

Subunit / interactions. Interacts with SYVN1 and VCP.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed abundantly in ovary and testis, and weakly in all other tissues tested.

Isoforms (3)

UniProt ID	Names	Canonical?
O00124-1	1, Long	yes
O00124-2	2, Short
O00124-3	3

RefSeq proteins (3): NP_001269118, NP_001269128, NP_005662* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001012	UBX_dom	Domain
IPR017247	UBXN8	Family
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR050730	UBX_domain-protein	Family

Pfam: PF00789

UniProt features (13 total): topological domain 3, splice variant 2, sequence variant 2, transmembrane region 2, chain 1, domain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00124-F1	77.88	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 167

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 156 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_SINGLE_FERTILIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, CGGAARNGGCNG_UNKNOWN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, chr8p12, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_FERTILIZATION, GOBP_ERAD_PATHWAY, DANG_BOUND_BY_MYC

GO Biological Process (5): single fertilization (GO:0007338), ERAD pathway (GO:0036503), DNA synthesis involved in DNA repair (GO:0000731), DNA-templated DNA replication (GO:0006261), RNA-templated DNA biosynthetic process (GO:0006278)

GO Molecular Function (10): protein-macromolecule adaptor activity (GO:0030674), ubiquitin binding (GO:0043130), nucleic acid binding (GO:0003676), RNA-directed DNA polymerase activity (GO:0003964), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), RNA-DNA hybrid ribonuclease activity (GO:0004523), protein binding (GO:0005515), transferase activity (GO:0016740), hydrolase activity (GO:0016787)

GO Cellular Component (6): ubiquitin ligase complex (GO:0000151), nucleoplasm (GO:0005654), nucleolus (GO:0005730), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA biosynthetic process	2
binding	2
catalytic activity	2
nuclear lumen	2
cellular anatomical structure	2
fertilization	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
DNA repair	1
DNA replication	1
protein binding	1
molecular adaptor activity	1
ubiquitin-like protein binding	1
RNA-templated DNA biosynthetic process	1
DNA polymerase activity	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism	1
intracellular protein-containing complex	1
transferase complex	1
intracellular membraneless organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

858 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBXN8	PPP2CB	P11082	962
UBXN8	FAF2	Q96CS3	697
UBXN8	UBXN2A	P68543	647
UBXN8	UBXN7	O94888	646
UBXN8	TBC1D17	Q9HA65	634
UBXN8	UBXN10	Q96LJ8	624
UBXN8	TBC1D15	Q8TC07	603
UBXN8	CHML	P26374	602
UBXN8	UBXN1	Q04323	597
UBXN8	UBXN6	Q9BZV1	590
UBXN8	REP15	Q6BDI9	581
UBXN8	UBXN11	Q5T124	574
UBXN8	UBXN4	Q92575	553
UBXN8	UBXN2B	Q14CS0	535
UBXN8	CHM	P24386	513

IntAct

70 interactions, top by confidence:

A	B	Type	Score
UBXN8	VCP	psi-mi:“MI:0914”(association)	0.690
UBXN8	VCP	psi-mi:“MI:2364”(proximity)	0.690
VCP	UBXN8	psi-mi:“MI:2364”(proximity)	0.690
UBXN8	VCP	psi-mi:“MI:0915”(physical association)	0.690
VCP	UBXN8	psi-mi:“MI:0915”(physical association)	0.690
VCP	UBXN8	psi-mi:“MI:0914”(association)	0.690
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
UBXN8	PGRMC2	psi-mi:“MI:0915”(physical association)	0.560
UBXN8	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
UBXN8	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
UBXN8	AQP6	psi-mi:“MI:0915”(physical association)	0.560
	UBXN8	psi-mi:“MI:0915”(physical association)	0.560
UBXN8	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
UBXN8	GJA8	psi-mi:“MI:0915”(physical association)	0.560
UBXN8	GFAP	psi-mi:“MI:0915”(physical association)	0.560
	UBXN8	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
TBC1D15	MYO9A	psi-mi:“MI:0914”(association)	0.530
TBC1D15	UBXN8	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
SELENOS	UBXN8	psi-mi:“MI:0914”(association)	0.350

BioGRID (124): UBXN8 (Affinity Capture-RNA), UBXN8 (Affinity Capture-RNA), UBXN8 (Affinity Capture-MS), UBXN8 (Two-hybrid), UBXN8 (Affinity Capture-Western), UBXN8 (Affinity Capture-MS), TBC1D15 (Affinity Capture-Western), VCP (Affinity Capture-MS), ATP4A (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), ELAVL2 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), RHBDD2 (Affinity Capture-MS), SLC38A1 (Affinity Capture-MS), TMEM165 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8ENT6, A2BGP7, A2CJ06, B1H1W9, F6RRD7, O00124, O55036, P54274, Q1LV50, Q1LWH4, Q1T7B8, Q28HU3, Q3KNJ2, Q3U1D0, Q3US16, Q4KLN8, Q4V832, Q5I0E6, Q5I2W8, Q5NVA9, Q5RA37, Q5RET9, Q5XI46, Q5ZIN2, Q6AYI4, Q6DRL4, Q6IQ49, Q6IRN0, Q6NV18, Q6P1H6, Q7Z2Z1, Q7Z4M0, Q8BJW7, Q8BKT3, Q8BMG1, Q8BMI4, Q8BQ33, Q8IXW5, Q8K1J5, Q8VC34

Diamond homologs: O00124, P54731, Q2TBH5, Q924K2, Q9QZ49, Q9UNN5, O94888, Q5REY7, Q6P5G6, Q9C5G7, F4JPR7, Q4V3D3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
UBXN8	“down-regulates quantity”	VCP	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 49 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of small molecules	7	5.5×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
transport across blood-brain barrier	5	21.3×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1259 predictions. Top by Δscore:

Variant	Effect	Δscore
8:30751514:GAAGG:G	donor_gain	1.0000
8:30751516:AGGGT:A	donor_loss	1.0000
8:30751517:GG:G	donor_gain	1.0000
8:30751518:GG:G	donor_gain	1.0000
8:30751518:GGT:G	donor_loss	1.0000
8:30751519:G:GA	donor_loss	1.0000
8:30751520:TAA:T	donor_loss	1.0000
8:30753024:T:TA	acceptor_gain	1.0000
8:30753027:T:G	acceptor_gain	1.0000
8:30753027:T:TA	acceptor_gain	1.0000
8:30753030:CTTAG:C	acceptor_loss	1.0000
8:30753032:TAG:T	acceptor_loss	1.0000
8:30753033:A:AG	acceptor_gain	1.0000
8:30753034:G:GT	acceptor_gain	1.0000
8:30753034:GAA:G	acceptor_gain	1.0000
8:30753101:AGAAG:A	donor_loss	1.0000
8:30753102:GAAG:G	donor_gain	1.0000
8:30753103:AAG:A	donor_loss	1.0000
8:30753104:AGGTA:A	donor_loss	1.0000
8:30753105:GGT:G	donor_loss	1.0000
8:30753106:G:C	donor_loss	1.0000
8:30753107:T:A	donor_loss	1.0000
8:30754760:GAAAT:G	donor_gain	1.0000
8:30754764:T:G	donor_gain	1.0000
8:30754764:T:TG	donor_gain	1.0000
8:30756884:GGAG:G	donor_gain	1.0000
8:30756885:GAGG:G	donor_gain	1.0000
8:30756888:G:GC	donor_loss	1.0000
8:30756889:T:G	donor_loss	1.0000
8:30760925:AAGAA:A	donor_gain	1.0000

AlphaMissense

1740 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:30763283:T:A	V194D	0.991
8:30763325:T:C	F208S	0.990
8:30763324:T:C	F208L	0.989
8:30763326:T:A	F208L	0.989
8:30763326:T:G	F208L	0.989
8:30763320:A:C	R206S	0.981
8:30763320:A:T	R206S	0.981
8:30766239:T:A	W220R	0.977
8:30766239:T:C	W220R	0.977
8:30766290:T:C	F237L	0.976
8:30766292:T:A	F237L	0.976
8:30766292:T:G	F237L	0.976
8:30766363:T:C	L261P	0.975
8:30766231:T:C	L217S	0.972
8:30766363:T:A	L261H	0.970
8:30763289:T:C	L196P	0.968
8:30763325:T:G	F208C	0.968
8:30763277:T:A	V192D	0.967
8:30763289:T:A	L196H	0.966
8:30763285:G:C	A195P	0.965
8:30763292:G:C	R197P	0.963
8:30763319:G:C	R206T	0.963
8:30751423:G:A	G39D	0.958
8:30766363:T:G	L261R	0.950
8:30766345:T:A	I255K	0.946
8:30766241:G:C	W220C	0.944
8:30766241:G:T	W220C	0.944
8:30763289:T:G	L196R	0.942
8:30766345:T:C	I255T	0.936
8:30766298:A:C	R239S	0.932

dbSNP variants (sampled 300 via entrez): RS1000006928 (8:30751541 C>G), RS1000054446 (8:30751905 T>C), RS1000065782 (8:30729652 C>G), RS1000179040 (8:30729304 C>T), RS1000197362 (8:30733932 A>G), RS1000230025 (8:30728099 G>C), RS1000295937 (8:30758413 T>C), RS1000406701 (8:30734693 C>G,T), RS1000456936 (8:30765367 C>T), RS1000511507 (8:30728527 G>A), RS1000561016 (8:30744077 C>T), RS1000653939 (8:30734919 A>T), RS1000674708 (8:30739704 A>C), RS1000708067 (8:30728372 C>T), RS1000837420 (8:30745742 C>T)

Disease associations

OMIM: gene MIM:602155 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	increases expression	1
abrine	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Hydrogen Peroxide	affects expression	1
Phenobarbital	affects expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Thapsigargin	increases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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