PRAME

Summary

PRAME (PRAME nuclear receptor transcriptional regulator, HGNC:9336) is a protein-coding gene on chromosome 22q11.22, encoding Melanoma antigen preferentially expressed in tumors (P78395). Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex, which mediates ubiquitination of target proteins, leading to their degradation.

This gene encodes an antigen that is preferentially expressed in human melanomas and that is recognized by cytolytic T lymphocytes. It is not expressed in normal tissues, except testis. The encoded protein acts as a repressor of retinoic acid receptor, and likely confers a growth advantage to cancer cells via this function. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 23532 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 9 total — 2 pathogenic
• MANE Select transcript: NM_206956

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9336
Approved symbol	PRAME
Name	PRAME nuclear receptor transcriptional regulator
Location	22q11.22
Locus type	gene with protein product
Status	Approved
Aliases	CT130
Ensembl gene	ENSG00000185686
Ensembl biotype	protein_coding
OMIM	606021
Entrez	23532

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000398741, ENST00000398743, ENST00000402697, ENST00000403441, ENST00000405655, ENST00000406503, ENST00000420709, ENST00000438888, ENST00000439106, ENST00000442481, ENST00000476336, ENST00000485532, ENST00000492657, ENST00000543184

RefSeq mRNA: 11 — MANE Select: NM_206956 NM_001291715, NM_001291716, NM_001291717, NM_001291719, NM_001318126, NM_001318127, NM_006115, NM_206953, NM_206954, NM_206955, NM_206956

CCDS: CCDS13801

Canonical transcript exons

ENST00000405655 — 6 exons

Exon	Start	End
ENSE00001534682	22557545	22557580
ENSE00001555086	22556812	22556909
ENSE00003592330	22549726	22550334
ENSE00003642784	22550767	22551089
ENSE00003669064	22547701	22548643
ENSE00003849945	22558971	22559265

Expression profiles

Bgee: expression breadth ubiquitous, 117 present calls, max score 98.00.

FANTOM5 (CAGE): breadth broad, TPM avg 22.4439 / max 828.2856, expressed in 332 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193280	9.6806	103
193284	9.6506	315
209405	1.8235	172
193283	0.6738	76
193282	0.4172	73
193281	0.1601	54
193278	0.0382	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	98.00	gold quality
left testis	UBERON:0004533	97.76	gold quality
testis	UBERON:0000473	97.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.20	gold quality
endometrium	UBERON:0001295	77.43	gold quality
right adrenal gland cortex	UBERON:0035827	77.03	gold quality
right adrenal gland	UBERON:0001233	73.05	gold quality
left ovary	UBERON:0002119	68.94	gold quality
ovary	UBERON:0000992	67.99	gold quality
left adrenal gland	UBERON:0001234	67.95	gold quality
adrenal gland	UBERON:0002369	65.54	gold quality
right ovary	UBERON:0002118	65.24	gold quality
left adrenal gland cortex	UBERON:0035825	65.10	gold quality
adult mammalian kidney	UBERON:0000082	59.75	gold quality
cortex of kidney	UBERON:0001225	58.53	gold quality
kidney	UBERON:0002113	57.16	gold quality
mucosa of transverse colon	UBERON:0004991	56.82	gold quality
vermiform appendix	UBERON:0001154	55.88	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	54.53	gold quality
metanephros cortex	UBERON:0010533	54.33	gold quality
smooth muscle tissue	UBERON:0001135	53.27	gold quality
lymph node	UBERON:0000029	52.89	gold quality
gastrocnemius	UBERON:0001388	52.31	gold quality
fallopian tube	UBERON:0003889	51.98	gold quality
left uterine tube	UBERON:0001303	51.57	gold quality
heart left ventricle	UBERON:0002084	51.18	gold quality
lower esophagus mucosa	UBERON:0035834	50.87	gold quality
colonic epithelium	UBERON:0000397	50.79	gold quality
body of uterus	UBERON:0009853	50.45	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-6	yes	78.93
E-GEOD-134144	yes	26.87
E-ANND-3	no	0.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, SOX9

miRNA regulators (miRDB)

21 targeting PRAME, 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-1305	99.91	71.43	3443
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-6867-3P	98.12	66.07	1305
HSA-MIR-3977	98.00	68.17	1500
HSA-MIR-618	97.62	67.46	861
HSA-MIR-4287	97.55	67.24	1247
HSA-MIR-4685-3P	97.55	67.35	1255
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-4764-3P	96.81	67.94	580
HSA-MIR-632	96.08	67.17	798
HSA-MIR-1238-3P	95.27	62.25	552
HSA-MIR-1231	95.10	65.63	663

Literature-anchored findings (GeneRIF, showing 40)

• expression of PRAME is an indicator of favorable prognosis and could be a useful tool for monitoring minimal residual disease in childhood AML. (PMID:11943337)
• PRAME gene expression in childhood acute lymphoblastic leukemia (PMID:12419593)
• PRAME is highly expressed in primary advanced neuroblastoma (PMID:15240516)
• The overexpression of PRAME protein frequently observed in human cancers confers growth or survival advantages by antagonizing retinoic acid receptor(RAR) signaling. (PMID:16179254)
• The results suggest that the analysis of PRAME protein may contribute for the distinction between normal and leukemic cells in chronic lymphoproliferative disorders(CLD), and that PRAME may be a potential target for therapy. (PMID:16620968)
• PRAME is expressed in acute myeloblastic leukaemia (PMID:16681423)
• Overexpression of PRAME was associated with childhood acute leukemia (PMID:16860864)
• PRAME is detected in one third of the cases with CLs. PRAME mRNA changes may be detected during the progression of these disorders and/or after therapy. PRAME mRNA may be a useful marker to detect the minimal residual disease and the response to therapy. (PMID:16914202)
• hypomethylation of PRAME up-regulates its expression in CML and might play a significant role in the progression of the disease (PMID:17382387)
• Changes in the methylation pattern in defined parts of the regulatory regions of PRAME are sufficient for its upregulation in cells usually not expressing the gene. (PMID:17534929)
• PRAME mRNA expression may be a useful prognostic and predictive marker for breast cancer. (PMID:17624586)
• PRAME expression is not associated with down-regulation of retinoic acid signaling in primary acute myeloid leukemia. (PMID:17693191)
• PRAME expression in acute leukemia may be a useful marker to detect the minimal residual disease and to determine the response to therapy in acute leukemia patients. (PMID:18088454)
• PRAME gene was overexpressed in adult acute leukemia patients and leukemia cell-lines. (PMID:18088461)
• We conclude that HCL and CLL differ in PRAME overexpression, and that basal normal expression of PRAME may limit its usefulness for following patients with minimal residual CLL or HCL. (PMID:18295331)
• Loss of PRAME is associated with childhood acute myeloid leukemia. (PMID:18452107)
• The significant inverse correlation between the degree of methylation and PRAME expression suggests a causal role of DNA methylation in PRAME regulation. (PMID:18587578)
• Multivariable analysis indicated that PRAME is an independent marker of shortened metastasis-free interval in patients who did not receive adjuvant chemotherapy. PRAME expression was associated with tumour grade and negative oestrogen receptor status (PMID:18648365)
• the 4 biomarkers CLU, ITGB3, PRAME and CAPG may be used as prognostic factors for patients with stage III serous ovarian adenocarcinomas. (PMID:18709641)
• Low PRAME expression defines a subgroup of patients with acute promyelocytic leukemia with a short relapse-free survival (PMID:18815192)
• quantified both WT1 and PRAME transcript levels in the bone marrow of AML patients. Dynamic patterns of WT1 and PRAME during follow-up showed that a consistent elevation or a rise over time to exceed the normal range predicted clinical relapse (PMID:18950857)
• These results provide evidence for spontaneous T cell reactivity against multiple epitopes of PRAME in lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia (PMID:18988867)
• Quantitative real-time PCR revealed that ZNF280A, ZNF280B, and PRAME mRNA expression was significantly lower in the 22q11 deletion cases compared to non-deleted cases (PMID:19027161)
• PRAME mRNA could be used to monitor minimal residual disease in newly diagnosed acute myeloid leukemia patients. (PMID:19035174)
• E2F4, PHACTR3, PRAME family member and CDH12 most probably play important role in non-small-cell lung cancer geneses (PMID:19473719)
• PRAME expression in DLBCL correlates with response to anthracycline containing chemotherapy. (PMID:19474511)
• PRAME inhibits myeloid differentiation in certain myeloid leukemias, and that its function in these cells is lineage and phenotype dependent. (PMID:19625708)
• The PRAME transcript was highly expressed in acute myeloid leukemia patients and was a favorable marker of prognosis. (PMID:20376794)
• The level of prame gene transcript increases in chronic myeloid leukemia which associates with disease progression. (PMID:20723287)
• Results showed the expression of MCSP and PRAME in conjunctival melanoma and benign conjunctival nevi and showed that MCSP and PRAME were differentially expressed in both and can help to differentiate the lesions diagnostically. (PMID:20805128)
• PRAME may be involved in the tumorigenic process in a wide range of cancers, at least in part by blocking the tumor suppressor pathway mediated by TRAIL expression. (PMID:20838376)
• The cytotoxic activity of our PRAME-specific CTLs was directed not only against leukemic blasts, but also against leukemic progenitor cells as assessed by colony-forming-inhibition assays, which have been implicated in leukemia relapse. (PMID:21278353)
• the expansion of the PRAME family occurred in both autosomes and sex chromosomes (PMID:21347312)
• PRAME plays an important role in disease progression in acute leukemia. (PMID:21550659)
• PRAME expression might be related to distinct patterns of tumorigenesis (PMID:21691740)
• The authors applied protein-complex purification strategies and identified PRAME as a substrate recognition subunit of a Cullin2-based E3 ubiquitin ligase. (PMID:21822215)
• Studies suggest that activated human gammadelta T cells can efficiently present PRAME and STEAP1-derived epitopes and allow breaking tolerance against these tumor-associated self-antigens. (PMID:21928126)
• PRAME effectively differentiates mullerian carcinoma from malignant mesothelioma at the mRNA and protein levels. (PMID:22261449)
• NYESO-1/LAGE-1s and PRAME are targets for antigen specific T cells in chondrosarcoma following treatment with 5-Aza-2-deoxycitabine (PMID:22384167)
• these results suggest that PRAME plays an important role in cell proliferation and disease progression in osteosarcoma. (PMID:22390931)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch73-174h16.4	ENSDARG00000036493

Paralogs (24): PRAMEF1 (ENSG00000116721), PRAMEF12 (ENSG00000116726), PRAMEF2 (ENSG00000120952), LRRC14 (ENSG00000160959), PRAMEF8 (ENSG00000182330), LRRC14B (ENSG00000185028), PRAMEF10 (ENSG00000187545), PRAMEF20 (ENSG00000204478), PRAMEF17 (ENSG00000204479), PRAMEF19 (ENSG00000204480), PRAMEF14 (ENSG00000204481), PRAMEF15 (ENSG00000204501), PRAMEF9 (ENSG00000204505), PRAMEF7 (ENSG00000204510), PRAMEF25 (ENSG00000229571), PRAMEF6 (ENSG00000232423), PRAMEF33 (ENSG00000237700), PRAMEF11 (ENSG00000239810), PRAMEF4 (ENSG00000243073), PRAMEF5 (ENSG00000270601), PRAMEF27 (ENSG00000274764), PRAMEF13 (ENSG00000279169), PRAMEF18 (ENSG00000279804), PRAMEF26 (ENSG00000280267)

Protein

Protein identifiers

Melanoma antigen preferentially expressed in tumors — P78395 (reviewed: P78395)

Alternative names: Opa-interacting protein 4, Preferentially expressed antigen of melanoma

All UniProt accessions (6): B5MCY4, B5MD04, E7EMH2, E7EW99, P78395, H7C2P3

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(PRAME) complex mediates ubiquitination and degradation of truncated MSRB1/SEPX1 selenoproteins produced by failed UGA/Sec decoding. In the nucleus, the CRL2(PRAME) complex is recruited to epigenetically and transcriptionally active promoter regions bound by nuclear transcription factor Y (NFY) and probably plays a role in chromstin regulation. Functions as a transcriptional repressor, inhibiting the signaling of retinoic acid through the retinoic acid receptors RARA, RARB and RARG: prevents retinoic acid-induced cell proliferation arrest, differentiation and apoptosis.

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 PRAME. Interacts with RARA (via the ligand-binding domain); the interaction is direct and ligand (retinoic acid)-dependent. Interacts with EZH2; required to repress RAR signaling.

Subcellular location. Nucleus. Chromosome. Cytoplasm. Golgi apparatus. Cell membrane.

Tissue specificity. Expressed in testis. Detected in samples of kidney, brain and skin.

Induction. Up-regulated in response to interferon gamma (IFNG) treatment and exposure to bacterial PAMPs (pathogen associated molecular patterns).

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. Tumor antigen recognized by cytolytic T lymphocytes.

Similarity. Belongs to the PRAME family.

RefSeq proteins (11): NP_001278644, NP_001278645, NP_001278646, NP_001278648, NP_001305055, NP_001305056, NP_006106, NP_996836, NP_996837, NP_996838, NP_996839* (*=MANE)

Domains & families (InterPro)

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

UniProt features (19 total): repeat 9, mutagenesis site 3, modified residue 2, sequence variant 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78395-F1	81.29	0.49

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 (2): 9, 16

Mutagenesis-validated functional residues (3):

Position	Phenotype
26–30	impaired formation of the crl2(prame) complex.
48–49	impaired formation of the crl2(prame) complex.
470–471	loss of interaction with rara and defective in repressing rara signaling.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 138 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, MODULE_52, LI_WILMS_TUMOR, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_RETINOIC_ACID_RECEPTOR_SIGNALING_PATHWAY, MODULE_16, HATADA_METHYLATED_IN_LUNG_CANCER_DN, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_4NM_UP, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_1_UP, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, MODULE_66, MODULE_118, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_RETINOIC_ACID_RECEPTOR_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS

GO Biological Process (10): protein polyubiquitination (GO:0000209), apoptotic process (GO:0006915), positive regulation of cell population proliferation (GO:0008284), cell differentiation (GO:0030154), 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), negative regulation of retinoic acid receptor signaling pathway (GO:0048387), protein ubiquitination (GO:0016567)

GO Molecular Function (3): nuclear retinoic acid receptor binding (GO:0042974), ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (9): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), Cul2-RING ubiquitin ligase complex (GO:0031462), chromosome (GO:0005694), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membrane-bounded organelle	2
protein ubiquitination	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cellular developmental process	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
retinoic acid receptor signaling pathway	1
regulation of retinoic acid receptor signaling pathway	1
negative regulation of intracellular signal transduction	1
protein modification by small protein conjugation	1
nuclear receptor binding	1
enzyme-substrate adaptor activity	1
binding	1
chromosome	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
membrane	1
cell periphery	1
cullin-RING ubiquitin ligase complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1548 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRAME	OIP5	O43482	799
PRAME	TRIP6	Q15654	774
PRAME	CTAG1A	P78358	728
PRAME	EXOSC8	Q96B26	721
PRAME	MAGEA3	P43357	693
PRAME	MAGEA4	P43358	670
PRAME	WT1	P19544	666
PRAME	PKM	P14618	665
PRAME	ZNF280B	Q86YH2	645
PRAME	MAGEA1	P43355	622
PRAME	ZNF280A	P59817	582
PRAME	HMMR	O75330	576
PRAME	MAGED4B	Q96JG8	571
PRAME	EZH2	Q15910	565
PRAME	CUL2	Q13617	563

IntAct

104 interactions, top by confidence:

A	B	Type	Score
PRAME	CUL2	psi-mi:“MI:0914”(association)	0.830
PRAME	ELOC	psi-mi:“MI:0914”(association)	0.740
PRAME	ELOC	psi-mi:“MI:0915”(physical association)	0.740
ELOC	PRAME	psi-mi:“MI:0915”(physical association)	0.740
ELOC	PRAME	psi-mi:“MI:0403”(colocalization)	0.740
IFT81	NDC80	psi-mi:“MI:0914”(association)	0.640
NPY2R	RTL8C	psi-mi:“MI:0914”(association)	0.530
ZNF562	ISLR	psi-mi:“MI:0914”(association)	0.530
DAAM2	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
AZIN2	OAZ2	psi-mi:“MI:0914”(association)	0.530
FSCN3	PRAME	psi-mi:“MI:0914”(association)	0.530
FOXD4	PDHX	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
AP5S1	AP5Z1	psi-mi:“MI:0914”(association)	0.530
COPS6	KLHL18	psi-mi:“MI:0914”(association)	0.530
PRAME	elc-1	psi-mi:“MI:0915”(physical association)	0.510
Hacd3	PRAME	psi-mi:“MI:0915”(physical association)	0.400
HSP90AB1	PRAME	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (152): PRAME (Affinity Capture-RNA), UBC (Biochemical Activity), PRAME (Affinity Capture-MS), PRAME (Affinity Capture-MS), PRAME (Affinity Capture-MS), PRAME (Two-hybrid), PRAME (Affinity Capture-MS), PRAME (Affinity Capture-MS), COPS2 (Affinity Capture-MS), CUL2 (Affinity Capture-MS), NOL11 (Affinity Capture-MS), PRAME (Affinity Capture-MS), PRAME (Affinity Capture-MS), PRAME (Affinity Capture-MS), PRAME (Affinity Capture-MS)

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

1 interactions.

A	Effect	B	Mechanism
SOX9	“down-regulates quantity by repression”	PRAME	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 124 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
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	5	13.9×	5e-03
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	6	12.4×	2e-03
Neddylation	10	6.7×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein neddylation	5	33.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2663782	NC_000022.10:g.(?21797384)(23630313_?)del	Pathogenic
816560	GRCh37/hg19 22q11.21-11.22(chr22:21947428-22962196)x1	Pathogenic

SpliceAI

793 predictions. Top by Δscore:

Variant	Effect	Δscore
22:22548639:CGTGC:C	acceptor_gain	1.0000
22:22549837:T:TA	donor_gain	1.0000
22:22549963:T:TA	donor_gain	1.0000
22:22550330:ACCTC:A	acceptor_gain	1.0000
22:22550331:CCTCC:C	acceptor_gain	1.0000
22:22550332:CTC:C	acceptor_gain	1.0000
22:22550333:TC:T	acceptor_gain	1.0000
22:22550334:CCTG:C	acceptor_gain	1.0000
22:22550334:CCTGT:C	acceptor_loss	1.0000
22:22550335:C:CC	acceptor_gain	1.0000
22:22550335:CTGT:C	acceptor_loss	1.0000
22:22550763:TTAC:T	donor_loss	1.0000
22:22550764:TA:T	donor_loss	1.0000
22:22550765:A:AT	donor_loss	1.0000
22:22550766:C:G	donor_loss	1.0000
22:22550779:T:TA	donor_gain	1.0000
22:22551088:CC:C	acceptor_gain	1.0000
22:22551089:CC:C	acceptor_gain	1.0000
22:22557543:A:AC	donor_gain	1.0000
22:22557544:C:CC	donor_gain	1.0000
22:22548641:TGC:T	acceptor_gain	0.9900
22:22548641:TGCCT:T	acceptor_loss	0.9900
22:22548642:GC:G	acceptor_gain	0.9900
22:22548643:CC:C	acceptor_gain	0.9900
22:22548644:C:A	acceptor_loss	0.9900
22:22548644:C:CC	acceptor_gain	0.9900
22:22548645:T:A	acceptor_loss	0.9900
22:22549721:CTCAC:C	donor_loss	0.9900
22:22549722:TCA:T	donor_loss	0.9900
22:22549723:CA:C	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000046814 (22:22557330 G>A,C,T), RS1000098577 (22:22557155 C>A,T), RS1000688492 (22:22552599 T>C), RS1000700157 (22:22550529 C>A), RS1000864300 (22:22555449 G>A), RS1000893984 (22:22555695 C>T), RS1001052180 (22:22556374 G>A,C), RS1001425615 (22:22560419 C>G), RS1001529107 (22:22557257 G>A), RS1001558502 (22:22557433 G>A,C), RS1001884392 (22:22558368 T>A,C,G), RS1001895556 (22:22556502 G>C), RS1002053842 (22:22552928 C>G), RS1002114853 (22:22555129 T>A,C), RS1002274514 (22:22558596 C>G,T)

Disease associations

OMIM: gene MIM:606021 | disease phenotypes: MIM:608363, MIM:611867

GenCC curated gene-disease

Mondo (2): chromosome 22q11.2 microduplication syndrome (MONDO:0012020), chromosome 22q11.2 deletion syndrome, distal (MONDO:0012740)

Orphanet (2): 22q11.2 duplication syndrome (Orphanet:1727), Distal 22q11.2 microdeletion syndrome (Orphanet:261330)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C567511	Chromosome 22q11.2 Deletion Syndrome, Distal (supp.)
C567224	Chromosome 22q11.2 Microduplication Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects binding, decreases reaction, increases reaction, affects cotreatment, decreases expression	4
bisphenol A	affects reaction, decreases reaction, affects binding, affects folding	2
bisphenol AF	affects reaction, affects folding, increases reaction, affects binding	2
Valproic Acid	increases expression, increases methylation	2
TAK-243	increases sumoylation	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
nickel acetate	decreases reaction, increases expression, decreases expression	1
perfluorobutanesulfonic acid	increases expression	1
bisphenol S	affects binding, decreases reaction	1
(+)-JQ1 compound	decreases expression	1
Alitretinoin	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cannabidiol	decreases expression	1
Choline	affects expression	1
Doxorubicin	increases expression	1
Progesterone	affects cotreatment, decreases expression	1
Tamoxifen	affects binding, decreases reaction	1
Tetrachlorodibenzodioxin	increases expression	1
Tretinoin	decreases activity, affects binding, increases reaction	1
Tunicamycin	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Metribolone	affects binding, affects folding, decreases reaction	1
Aflatoxin B1	decreases methylation	1
Cyproterone Acetate	affects binding, affects folding, increases reaction	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7J7	Ubigene A-375 PRAME KO	Cancer cell line	Female
CVCL_D8TN	Ubigene HCT 116 PRAME KO	Cancer cell line	Male
CVCL_E1GM	Abcam U2OS PRAME KO	Cancer cell line	Female

Clinical trials (associated diseases)

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