PRAMEF6

Summary

PRAMEF6 (PRAME family member 6, HGNC:30583) is a protein-coding gene on chromosome 1p36.21, encoding PRAME family member 6 (Q5VXH4). Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex, which mediates ubiquitination of target proteins, leading to their degradation.

Enables ubiquitin-like ligase-substrate adaptor activity. Involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Part of Cul2-RING ubiquitin ligase complex.

Source: NCBI Gene 440561 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_001010889

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30583
Approved symbol	PRAMEF6
Name	PRAME family member 6
Location	1p36.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000232423
Ensembl biotype	protein_coding
Entrez	440561

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000376189, ENST00000415464

RefSeq mRNA: 1 — MANE Select: NM_001010889 NM_001010889

CCDS: CCDS30594

Canonical transcript exons

ENST00000376189 — 4 exons

Exon	Start	End
ENSE00001628788	12942232	12942540
ENSE00001635069	12947517	12947580
ENSE00001637965	12940984	12941565
ENSE00001646667	12938472	12939236

Expression profiles

Bgee: expression breadth tissue_specific, 1 present calls, max score 37.20.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.21	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
liver	UBERON:0002107	30.17	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.20	gold quality
ectocervix	UBERON:0012249	28.24	silver quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
urinary bladder	UBERON:0001255	27.57	gold quality
placenta	UBERON:0001987	27.38	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.88	gold quality
leukocyte	CL:0000738	26.84	gold quality
monocyte	CL:0000576	26.76	gold quality
calcaneal tendon	UBERON:0003701	26.72	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
right lobe of liver	UBERON:0001114	26.36	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
cortex of kidney	UBERON:0001225	24.93	gold quality
pancreas	UBERON:0001264	24.69	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting PRAMEF6, 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-3156-3P	99.76	66.72	939
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-198	98.70	67.32	920
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-1265	98.36	66.46	598
HSA-MIR-6818-5P	97.50	67.10	1167
HSA-MIR-7106-3P	97.33	65.33	644

Cross-species orthologs

125 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch73-174h16.4	ENSDARG00000036493
mus_musculus	Pramel6	ENSMUSG00000025838
mus_musculus	Pramel7	ENSMUSG00000025839
mus_musculus	Pramel13	ENSMUSG00000028591
mus_musculus	Pramel27	ENSMUSG00000029451
mus_musculus	Pramel17	ENSMUSG00000035201
mus_musculus	Pramel5	ENSMUSG00000036749
mus_musculus	Pramel18	ENSMUSG00000037028
mus_musculus	Pramel32	ENSMUSG00000038330
mus_musculus	Pramel1	ENSMUSG00000041805
mus_musculus	C130073F10Rik	ENSMUSG00000046133
mus_musculus	Pramel29	ENSMUSG00000046262
mus_musculus	Pramel24	ENSMUSG00000046435
mus_musculus	Pramel12	ENSMUSG00000046862
mus_musculus	Oog4	ENSMUSG00000047799
mus_musculus	Oog3	ENSMUSG00000050810
mus_musculus	Pramel26	ENSMUSG00000059218
mus_musculus	Pramel51	ENSMUSG00000066027
mus_musculus	Oog2	ENSMUSG00000066030
mus_musculus	Pramel25	ENSMUSG00000066031
mus_musculus	Pramel21	ENSMUSG00000066688
mus_musculus	Gm13040	ENSMUSG00000070616
mus_musculus	Pramel23	ENSMUSG00000070617
mus_musculus	Pramel20	ENSMUSG00000070618
mus_musculus	Pramel31	ENSMUSG00000070619
mus_musculus	Pramel48	ENSMUSG00000070677
mus_musculus	Pramel34	ENSMUSG00000070686
mus_musculus	Pramel19	ENSMUSG00000070890
mus_musculus	Pramel55	ENSMUSG00000072813
mus_musculus	Pramel54	ENSMUSG00000072814
mus_musculus	Pramel53	ENSMUSG00000072821
mus_musculus	Pramel37	ENSMUSG00000072822
mus_musculus	Pramel15	ENSMUSG00000073721
mus_musculus	Pramel61	ENSMUSG00000073723
mus_musculus	Pramel4	ENSMUSG00000073724
mus_musculus	Pramel41	ENSMUSG00000074011
		ENSMUSG00000074720
mus_musculus	Pramel30	ENSMUSG00000078508
mus_musculus	Pramel14	ENSMUSG00000078509
mus_musculus	Pramel28	ENSMUSG00000078510
mus_musculus	Pramel16	ENSMUSG00000078511
mus_musculus	Pramel11	ENSMUSG00000078512
mus_musculus	Pramel22	ENSMUSG00000078513
mus_musculus	Prame62	ENSMUSG00000078625
mus_musculus	Gm12790	ENSMUSG00000078626
mus_musculus	Pramel57	ENSMUSG00000079423
mus_musculus	Pramel47	ENSMUSG00000079424
		ENSMUSG00000091585
mus_musculus	Pramel45	ENSMUSG00000092166
mus_musculus	Pramel49	ENSMUSG00000094043
		ENSMUSG00000094172
mus_musculus	Pramel44	ENSMUSG00000094195
		ENSMUSG00000094303
		ENSMUSG00000094337
		ENSMUSG00000094383
		ENSMUSG00000094474
		ENSMUSG00000094722
		ENSMUSG00000094741
		ENSMUSG00000094791
		ENSMUSG00000094836
		ENSMUSG00000094855
		ENSMUSG00000094887
mus_musculus	Pramel42	ENSMUSG00000095074
mus_musculus	Gm13043	ENSMUSG00000095409
		ENSMUSG00000095475
mus_musculus	Pramel43	ENSMUSG00000095503
		ENSMUSG00000095505
		ENSMUSG00000095523
		ENSMUSG00000095570
		ENSMUSG00000095666
mus_musculus	Pramel40	ENSMUSG00000095718
		ENSMUSG00000095763
mus_musculus	Pramel56	ENSMUSG00000095954
mus_musculus	Pramel60	ENSMUSG00000095996
mus_musculus	Pramel33	ENSMUSG00000096044
mus_musculus	Pramel46	ENSMUSG00000096066
mus_musculus	Pramel50	ENSMUSG00000096139
mus_musculus	Gm13057	ENSMUSG00000096154
mus_musculus	Pramel36	ENSMUSG00000096230
		ENSMUSG00000096236
mus_musculus	Pramel38	ENSMUSG00000096259
mus_musculus	Gm2042	ENSMUSG00000096276
		ENSMUSG00000096550
mus_musculus	Oog1	ENSMUSG00000096576
		ENSMUSG00000096680
		ENSMUSG00000096728
		ENSMUSG00000096756
mus_musculus	Pramel35	ENSMUSG00000107392
rattus_norvegicus	Pramel6	ENSRNOG00000021920
rattus_norvegicus	Pramel7	ENSRNOG00000021949
rattus_norvegicus	Pramef25	ENSRNOG00000027000
rattus_norvegicus	Oog3	ENSRNOG00000027142
rattus_norvegicus	Pramef8	ENSRNOG00000027278
rattus_norvegicus	Pramef27	ENSRNOG00000027328
rattus_norvegicus	Oog1	ENSRNOG00000033000
rattus_norvegicus	Pramef12	ENSRNOG00000037035
rattus_norvegicus	Oog3l1	ENSRNOG00000037039
rattus_norvegicus	Pramef17	ENSRNOG00000042820
rattus_norvegicus	Pramel36	ENSRNOG00000043130
rattus_norvegicus	Oog3l2	ENSRNOG00000045614
rattus_norvegicus	Pramel36l1	ENSRNOG00000046931
rattus_norvegicus	LOC120103107	ENSRNOG00000047341
rattus_norvegicus	Pramef20	ENSRNOG00000053942
rattus_norvegicus	LOC134481896	ENSRNOG00000062749
rattus_norvegicus	Pramel53l1	ENSRNOG00000063444
rattus_norvegicus	LOC120096511	ENSRNOG00000063633
rattus_norvegicus	Pramel36l1	ENSRNOG00000064574
rattus_norvegicus	Pramef20l1	ENSRNOG00000065680
rattus_norvegicus		ENSRNOG00000065869
rattus_norvegicus	LOC134481897	ENSRNOG00000067003
rattus_norvegicus	Pramef8l2	ENSRNOG00000067042
rattus_norvegicus	Pramel34	ENSRNOG00000067111
rattus_norvegicus	Pramef5	ENSRNOG00000067307
rattus_norvegicus	Pramef20-ps1	ENSRNOG00000067899
rattus_norvegicus		ENSRNOG00000071611
rattus_norvegicus		ENSRNOG00000072535
rattus_norvegicus		ENSRNOG00000073402
rattus_norvegicus		ENSRNOG00000073978
rattus_norvegicus		ENSRNOG00000075698
rattus_norvegicus		ENSRNOG00000077508
rattus_norvegicus		ENSRNOG00000083237
rattus_norvegicus		ENSRNOG00000084642
rattus_norvegicus		ENSRNOG00000086814
rattus_norvegicus		ENSRNOG00000088869
rattus_norvegicus		ENSRNOG00000089019

Paralogs (24): PRAMEF1 (ENSG00000116721), PRAMEF12 (ENSG00000116726), PRAMEF2 (ENSG00000120952), LRRC14 (ENSG00000160959), PRAMEF8 (ENSG00000182330), LRRC14B (ENSG00000185028), PRAME (ENSG00000185686), PRAMEF10 (ENSG00000187545), PRAMEF20 (ENSG00000204478), PRAMEF17 (ENSG00000204479), PRAMEF19 (ENSG00000204480), PRAMEF14 (ENSG00000204481), PRAMEF15 (ENSG00000204501), PRAMEF9 (ENSG00000204505), PRAMEF7 (ENSG00000204510), PRAMEF25 (ENSG00000229571), PRAMEF33 (ENSG00000237700), PRAMEF11 (ENSG00000239810), PRAMEF4 (ENSG00000243073), PRAMEF5 (ENSG00000270601), PRAMEF27 (ENSG00000274764), PRAMEF13 (ENSG00000279169), PRAMEF18 (ENSG00000279804), PRAMEF26 (ENSG00000280267)

Protein

Protein identifiers

PRAME family member 6 — Q5VXH4 (reviewed: Q5VXH4)

All UniProt accessions (1): Q5VXH4

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex, which mediates ubiquitination of target proteins, leading to their degradation. The CRL2(PRAMEF6) complex mediates ubiquitination and degradation of truncated MSRB1/SEPX1 selenoproteins produced by failed UGA/Sec decoding.

Subunit / interactions. Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter PRAMEF6.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the PRAME family.

RefSeq proteins (1): NP_001010889* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026271	PRAME	Family
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050694	LRRC14/PRAME	Family

UniProt features (11 total): repeat 9, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VXH4-F1	84.85	0.56

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEIN_CATABOLIC_PROCESS, GOCC_TRANSFERASE_COMPLEX, GOBP_PROTEOLYSIS, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, GOCC_UBIQUITIN_LIGASE_COMPLEX, chr1p36, GOBP_POSITIVE_REGULATION_OF_CELL_POPULATION_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOCC_CUL2_RING_UBIQUITIN_LIGASE_COMPLEX, MIR6818_5P, MIR7106_3P

GO Biological Process (6): positive regulation of cell population proliferation (GO:0008284), protein ubiquitination (GO:0016567), negative regulation of apoptotic process (GO:0043066), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), negative regulation of cell differentiation (GO:0045596), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (1): ubiquitin-like ligase-substrate adaptor activity (GO:1990756)

GO Cellular Component (2): cytoplasm (GO:0005737), Cul2-RING ubiquitin ligase complex (GO:0031462)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
protein modification by small protein conjugation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
cell differentiation	1
regulation of cell differentiation	1
negative regulation of cellular process	1
negative regulation of developmental process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
enzyme-substrate adaptor activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

2129 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRAMEF6	MSRB1	Q9NZV6	550
PRAMEF6	WFDC3	Q8IUB2	479
PRAMEF6	TMEM92	Q6UXU6	471
PRAMEF6	LEUTX	A8MZ59	447
PRAMEF6	KLHDC3	Q9BQ90	445
PRAMEF6	TRIM43	Q96BQ3	418
PRAMEF6	MBD3L2	Q8NHZ7	418
PRAMEF6	KLHDC2	Q9Y2U9	412
PRAMEF6	FEM1C	Q96JP0	403
PRAMEF6	APPBP2	Q92624	398
PRAMEF6	SELENOV	P59797	378
PRAMEF6	ZNF155	Q12901	371
PRAMEF6	MYO1G	B0I1T2	348
PRAMEF6	ZSCAN4	Q8NAM6	321
PRAMEF6	SEPHS2	Q99611	321

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A0G2JMD5, A1Z198, A3QJZ6, A3QJZ7, A6NGN4, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5G7, H0Y7S4, O60809, O60810, O60811, O60813, O95521, O95522, P0DUQ1, P0DUQ2, P78395, Q0GKD5, Q288C4, Q2LKU9, Q2LKV5, Q2LKW6, Q3TKR3, Q3UWY1, Q5SWL7, Q5SWL8, Q5TYX0, Q5VT98, Q5VTA0, Q5VWM3, Q5VWM4, Q5VWM6, Q5VXH4, Q5VXH5, Q66X05, Q66X19

Diamond homologs: A0A0G2JMD5, A3QJZ6, A3QJZ7, A6NGN4, E9Q5G7, H0Y7S4, O60809, O60810, O60811, O60813, O95521, O95522, P0DUQ1, P0DUQ2, P78395, Q3UWY1, Q5SWL7, Q5SWL8, Q5TYX0, Q5VT98, Q5VTA0, Q5VWM3, Q5VWM4, Q5VWM6, Q5VXH4, Q5VXH5, Q7TPX8, Q810Y8, Q99MW3, Q3UJB3, A5PJJ5, Q15048, Q569B5, A6NHZ5, Q1L8H0, Q640Z9, Q8VC16, P59047, Q7TSF4, Q8NAA5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

703 predictions. Top by Δscore:

Variant	Effect	Δscore
1:12939234:CAG:C	acceptor_gain	1.0000
1:12939237:C:CC	acceptor_gain	1.0000
1:12940978:CCTCA:C	donor_loss	1.0000
1:12940979:CTCA:C	donor_loss	1.0000
1:12940980:TCAC:T	donor_loss	1.0000
1:12940982:A:T	donor_loss	1.0000
1:12940983:CCTG:C	donor_loss	1.0000
1:12941561:ACCTC:A	acceptor_gain	1.0000
1:12939232:GACAG:G	acceptor_gain	0.9900
1:12939235:AG:A	acceptor_gain	0.9900
1:12939235:AGCTG:A	acceptor_loss	0.9900
1:12939236:GCT:G	acceptor_loss	0.9900
1:12939238:T:A	acceptor_loss	0.9900
1:12940981:CA:C	donor_loss	0.9900
1:12940982:A:C	donor_loss	0.9900
1:12941221:TCC:T	donor_gain	0.9900
1:12942227:CTCA:C	donor_loss	0.9900
1:12942228:TCA:T	donor_loss	0.9900
1:12942228:TCAC:T	donor_loss	0.9900
1:12942229:CAC:C	donor_loss	0.9900
1:12942230:AC:A	donor_loss	0.9900
1:12942231:C:A	donor_loss	0.9900
1:12942545:C:CT	acceptor_gain	0.9900
1:12942545:C:T	acceptor_gain	0.9900
1:12945351:A:AC	donor_gain	0.9900
1:12945352:C:CC	donor_gain	0.9900
1:12938853:T:A	donor_gain	0.9800
1:12939233:ACAG:A	acceptor_gain	0.9800
1:12939234:CAGC:C	acceptor_gain	0.9800
1:12942546:A:T	acceptor_gain	0.9800

AlphaMissense

3141 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:12938849:A:C	S419R	0.920
1:12938849:A:T	S419R	0.920
1:12938851:T:G	S419R	0.920
1:12942336:G:C	F61L	0.919
1:12942336:G:T	F61L	0.919
1:12942338:A:G	F61L	0.919
1:12938942:A:C	N388K	0.910
1:12938942:A:T	N388K	0.910
1:12941181:A:C	F224L	0.896
1:12941181:A:T	F224L	0.896
1:12941183:A:G	F224L	0.896
1:12942344:A:G	W59R	0.895
1:12942344:A:T	W59R	0.895
1:12942411:G:C	F36L	0.883
1:12942411:G:T	F36L	0.883
1:12942413:A:G	F36L	0.883
1:12941013:G:C	F280L	0.882
1:12941013:G:T	F280L	0.882
1:12941015:A:G	F280L	0.882
1:12939021:A:G	I362T	0.873
1:12941517:G:C	F112L	0.867
1:12941517:G:T	F112L	0.867
1:12941519:A:G	F112L	0.867
1:12938747:G:C	F453L	0.863
1:12938747:G:T	F453L	0.863
1:12938749:A:G	F453L	0.863
1:12941182:A:G	F224S	0.855
1:12939204:A:T	I301K	0.854
1:12942387:G:C	F44L	0.854
1:12942387:G:T	F44L	0.854

dbSNP variants (sampled 300 via entrez): RS1003798207 (1:12941017 G>A), RS1003871612 (1:12942850 A>G), RS1007719476 (1:12938547 C>T), RS1008631810 (1:12945988 A>G), RS1011593891 (1:12938757 C>T), RS1012425474 (1:12942040 G>A), RS1013794279 (1:12944098 G>A), RS1014137614 (1:12942951 C>A,T), RS1014542588 (1:12938034 G>C,T), RS1015776624 (1:12939420 C>G), RS1015830449 (1:12941111 C>T), RS10158787 (1:12943316 T>A), RS10159295 (1:12943848 G>A), RS1017229647 (1:12947980 T>C), RS1019027575 (1:12938432 T>G)

Disease associations

OMIM: gene `` | 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

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Testosterone	increases expression	1
Tretinoin	increases expression	1

Clinical trials (associated diseases)

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