PRAF2

Summary

PRAF2 (PRA1 domain family member 2, HGNC:28911) is a protein-coding gene on chromosome Xp11.23, encoding PRA1 family protein 2 (O60831). May be involved in ER/Golgi transport and vesicular traffic.

Predicted to be involved in L-glutamate transmembrane transport. Predicted to be located in endosome membrane. Predicted to be active in several cellular components, including GABA-ergic synapse; glutamatergic synapse; and postsynapse.

Source: NCBI Gene 11230 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 24 total
• MANE Select transcript: NM_007213

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28911
Approved symbol	PRAF2
Name	PRA1 domain family member 2
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Aliases	JM4, Yip6a
Ensembl gene	ENSG00000243279
Ensembl biotype	protein_coding
OMIM	300840
Entrez	11230

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000376386, ENST00000553851, ENST00000618882, ENST00000867496

RefSeq mRNA: 1 — MANE Select: NM_007213 NM_007213

CCDS: CCDS14317

Canonical transcript exons

ENST00000553851 — 3 exons

Exon	Start	End
ENSE00003993756	49073809	49074002
ENSE00003993763	49071161	49072008
ENSE00003993767	49072433	49072650

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.1329 / max 1317.8193, expressed in 1687 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199230	66.1329	1687

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	97.08	gold quality
pituitary gland	UBERON:0000007	97.01	gold quality
hypothalamus	UBERON:0001898	96.65	gold quality
prefrontal cortex	UBERON:0000451	96.57	gold quality
stromal cell of endometrium	CL:0002255	96.45	gold quality
superior frontal gyrus	UBERON:0002661	96.41	gold quality
frontal cortex	UBERON:0001870	96.31	gold quality
substantia nigra	UBERON:0002038	96.05	gold quality
right frontal lobe	UBERON:0002810	95.98	gold quality
anterior cingulate cortex	UBERON:0009835	95.91	gold quality
cerebral cortex	UBERON:0000956	95.90	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.89	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.77	gold quality
temporal lobe	UBERON:0001871	95.75	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.74	gold quality
ascending aorta	UBERON:0001496	95.73	gold quality
amygdala	UBERON:0001876	95.73	gold quality
thoracic aorta	UBERON:0001515	95.72	gold quality
Ammon’s horn	UBERON:0001954	95.69	gold quality
primary visual cortex	UBERON:0002436	95.61	gold quality
nucleus accumbens	UBERON:0001882	95.59	gold quality
caudate nucleus	UBERON:0001873	95.58	gold quality
putamen	UBERON:0001874	95.58	gold quality
brain	UBERON:0000955	95.35	gold quality
left coronary artery	UBERON:0001626	95.02	gold quality
descending thoracic aorta	UBERON:0002345	94.99	gold quality
endocervix	UBERON:0000458	94.83	gold quality
body of uterus	UBERON:0009853	94.63	gold quality
smooth muscle tissue	UBERON:0001135	94.28	gold quality
right adrenal gland	UBERON:0001233	94.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	25.96
E-ANND-3	yes	11.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting PRAF2, 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-4682	100.00	68.89	1258
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053

Literature-anchored findings (GeneRIF, showing 9)

• PRAF2 (JM4) is CCR5-interacting protein, which is suggested to function in trafficking and membrane localisation of the receptor. (PMID:15757671)
• CCR5-interacting PRAF2 protein is expressed in several human tissues with a possible function in ER/Golgi transport and vesicular traffic. (PMID:16481131)
• PRAF2 has a role in progression of neuroblastoma (PMID:17975142)
• The expression of PRAF2 in specific regions of the brain including SVs suggest an important physiological function for this novel protein, possibly by participating in multiple aspects of SV maturation, transport, and signal transmission. (PMID:18395978)
• PRAF2 expression is elevated in various tumors with exceptionally high expression in malignant gliomas, and may thus presents a candidate molecular target for therapeutic intervention. (PMID:20412121)
• Praf2 is a novel Bcl-xL/Bcl-2 interacting protein with the ability to modulate survival of cancer cells (PMID:21203533)
• PRAF2 plays an essential role in neuroblastoma tumorigenesis and metastasis. (PMID:23440329)
• PRAF2 could be used as a potential prognostic biomarker and represent a potential therapeutic target for ESCC. (PMID:31200670)
• Control of CCR5 Cell-Surface Targeting by the PRAF2 Gatekeeper. (PMID:38139265)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	praf2	ENSDARG00000032535
mus_musculus	Praf2	ENSMUSG00000031149
rattus_norvegicus	Praf2	ENSRNOG00000057147
drosophila_melanogaster	Jwa	FBGN0032704
caenorhabditis_elegans		WBGENE00017070

Paralogs (1): ARL6IP5 (ENSG00000144746)

Protein

Protein identifiers

PRA1 family protein 2 — O60831 (reviewed: O60831)

All UniProt accessions (2): A6NP52, O60831

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in ER/Golgi transport and vesicular traffic. Plays a proapoptotic role in cerulenin-induced neuroblastoma apoptosis.

Subunit / interactions. Interacts with CCR5 and GDE1.

Subcellular location. Endosome membrane.

Tissue specificity. Strong expression in the brain, small intestine, lung, spleen, and pancreas as well as in tumor tissues of the breast, colon, lung and ovary, with a weaker expression in normal tissues of the same patient. High expression in neuroblastic tumors. Strongly expressed in Purkinje cells and more moderately in cells of the molecular and the granular layers in the cerebellum. Detected in neuronal cells, but not in non-neuronal cells in the cerebral cortex, hippocampus, and lateral ventricles.

Similarity. Belongs to the PRA1 family.

RefSeq proteins (1): NP_009144* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004895	Prenylated_rab_accept_PRA1	Family

Pfam: PF03208

UniProt features (11 total): topological domain 5, transmembrane region 4, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60831-F1	83.44	0.45

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 131 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, BROWNE_HCMV_INFECTION_48HR_DN, DOANE_RESPONSE_TO_ANDROGEN_DN, GOBP_AMINO_ACID_TRANSPORT, ZIC1_01, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_DICARBOXYLIC_ACID_TRANSPORT, ONDER_CDH1_TARGETS_2_UP, YAMASHITA_METHYLATED_IN_PROSTATE_CANCER, GOBP_ACIDIC_AMINO_ACID_TRANSPORT, NKX22_01, LIU_CMYB_TARGETS_UP

GO Biological Process (2): protein transport (GO:0015031), L-glutamate transmembrane transport (GO:0015813)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): endosome membrane (GO:0010008), membrane (GO:0016020), presynapse (GO:0098793), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synapse	4
cellular anatomical structure	3
transport	1
intracellular protein localization	1
establishment of protein localization	1
L-glutamate import	1
L-alpha-amino acid transmembrane transport	1
binding	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

412 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRAF2	RABAC1	Q9UI14	667
PRAF2	CCDC22	O60826	646
PRAF2	ITIH4	Q14624	633
PRAF2	GABBR2	O75899	418
PRAF2	GABBR1	Q9UBS5	414
PRAF2	LRRC20	Q8TCA0	356
PRAF2	TMEM69	Q5SWH9	352
PRAF2	RAB43	Q86YS6	337
PRAF2	H0YNG3	H0YNG3	331
PRAF2	BUD13	Q9BRD0	324
PRAF2	CCDC71	Q8IV32	319
PRAF2	NLE1	Q9NVX2	304
PRAF2	CSTL1	Q9H114	302
PRAF2	YIF1B	Q5BJH7	297
PRAF2	CAMK1G	Q96NX5	295

IntAct

166 interactions, top by confidence:

A	B	Type	Score
PRAF2	ARL6IP5	psi-mi:“MI:0915”(physical association)	0.620
ARL6IP5	PRAF2	psi-mi:“MI:0915”(physical association)	0.620
PRAF2	ARL6IP5	psi-mi:“MI:0403”(colocalization)	0.620
PRAF2	TMX2	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	GJA8	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	ABHD16A	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	NDRG4	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	MCEMP1	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	CLEC10A	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	RNF5	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	HIBADH	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	HSD17B11	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	CIAO2A	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	GJA5	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	ZDHHC15	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	AQP6	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	REEP4	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	CD79A	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	PRAF2	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	SLC10A6	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	GPR152	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
PRAF2	AGR3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (148): PRAF2 (Affinity Capture-MS), PRAF2 (Affinity Capture-MS), PRAF2 (Affinity Capture-MS), PRAF2 (Affinity Capture-MS), PRAF2 (Affinity Capture-MS), PRAF2 (Affinity Capture-MS), PRAF2 (Affinity Capture-MS), PRAF2 (Affinity Capture-MS), PRAF2 (Affinity Capture-MS), PRAF2 (Proximity Label-MS), PRAF2 (Proximity Label-MS), PRAF2 (Affinity Capture-MS), PRAF2 (Affinity Capture-MS), PRAF2 (Affinity Capture-MS), PRAF2 (Affinity Capture-MS)

ESM2 similar proteins: A1A4L8, A1A4Q9, A1L134, A2BDX3, A5YM72, A6H707, B0BLZ5, B0JZP3, G3MZR2, O43292, O60831, O89109, P70295, Q11130, Q2TBP5, Q2V8X7, Q32NY4, Q3UPE3, Q4R4E4, Q4R4I9, Q5XIE1, Q5ZIW1, Q66HR0, Q6IQX7, Q6NRK8, Q6P2H8, Q7L1V2, Q80ZW2, Q86VU5, Q8IZ52, Q8N3Y3, Q8NE01, Q8NF37, Q8NI29, Q8TAC2, Q8TCD5, Q8TD43, Q8WUY1, Q92839, Q96DE0

Diamond homologs: O60831, O75915, Q2KHX3, Q4R4I9, Q4R4R4, Q56P28, Q5E9M1, Q5F433, Q5R4X8, Q8R5J9, Q9ES40, Q9JIG8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 116 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
RHOQ GTPase cycle	5	13.5×	8e-04
Neutrophil degranulation	10	3.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

457 predictions. Top by Δscore:

Variant	Effect	Δscore
X:49072402:T:A	donor_gain	1.0000
X:49072431:A:AC	donor_gain	1.0000
X:49072432:C:CC	donor_gain	1.0000
X:49072432:CGAAG:C	donor_gain	1.0000
X:49072009:C:CC	acceptor_gain	0.9900
X:49072378:G:A	donor_gain	0.9900
X:49072646:CGTAC:C	acceptor_gain	0.9900
X:49072647:GTACC:G	acceptor_loss	0.9900
X:49072649:ACCT:A	acceptor_loss	0.9900
X:49072652:T:G	acceptor_loss	0.9900
X:49073779:C:A	donor_gain	0.9900
X:49073798:C:CA	donor_gain	0.9900
X:49073802:C:A	donor_gain	0.9900
X:49073803:CCTCA:C	donor_loss	0.9900
X:49073804:CTCAC:C	donor_loss	0.9900
X:49073805:TCA:T	donor_loss	0.9900
X:49073807:A:AC	donor_gain	0.9900
X:49073807:A:AT	donor_loss	0.9900
X:49073807:AC:A	donor_gain	0.9900
X:49073808:C:CC	donor_gain	0.9900
X:49073808:C:CG	donor_loss	0.9900
X:49073808:CC:C	donor_gain	0.9900
X:49073808:CCCGG:C	donor_gain	0.9900
X:49072006:TCA:T	acceptor_gain	0.9800
X:49072007:CA:C	acceptor_gain	0.9800
X:49072007:CAC:C	acceptor_gain	0.9800
X:49072383:AAG:A	donor_gain	0.9800
X:49072648:TAC:T	acceptor_gain	0.9800
X:49072649:AC:A	acceptor_gain	0.9800
X:49072650:CC:C	acceptor_gain	0.9800

AlphaMissense

1112 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:49071979:G:T	R143S	0.993
X:49073847:G:C	N47K	0.993
X:49073847:G:T	N47K	0.993
X:49073868:G:C	N40K	0.991
X:49073868:G:T	N40K	0.991
X:49071993:G:T	A138D	0.990
X:49073866:A:G	L41P	0.990
X:49071985:G:T	R141S	0.989
X:49071962:C:A	K148N	0.988
X:49071962:C:G	K148N	0.988
X:49071964:T:C	K148E	0.979
X:49073869:T:A	N40I	0.978
X:49073882:G:T	R36S	0.978
X:49073861:A:C	Y43D	0.977
X:49071916:C:G	G164R	0.976
X:49073878:A:T	V37D	0.976
X:49071994:C:G	A138P	0.974
X:49073853:T:A	Q45H	0.974
X:49073853:T:G	Q45H	0.974
X:49073866:A:T	L41H	0.972
X:49073960:G:T	R10S	0.970
X:49073943:A:C	F15L	0.968
X:49073943:A:T	F15L	0.968
X:49073945:A:G	F15L	0.968
X:49071978:C:A	R143L	0.967
X:49073858:A:C	Y44D	0.964
X:49073881:C:G	R36P	0.964
X:49071918:A:T	M163K	0.963
X:49071963:T:A	K148M	0.963
X:49071985:G:C	R141G	0.963

dbSNP variants (sampled 300 via entrez): RS1001644426 (X:49070982 G>A), RS1001695237 (X:49071299 G>A), RS1002697795 (X:49073363 T>A), RS1003646033 (X:49074842 G>A), RS1003698454 (X:49075334 G>A), RS1006211039 (X:49072215 G>A), RS1007214496 (X:49074221 G>C), RS1007832572 (X:49073859 G>A), RS1010340138 (X:49071345 C>T), RS1010808702 (X:49071774 C>G), RS1011394293 (X:49073670 C>T), RS1011762525 (X:49073405 G>A), RS1017909175 (X:49074269 C>T), RS1020287820 (X:49071055 G>A), RS1020758653 (X:49071355 G>A,T)

Disease associations

OMIM: gene MIM:300840 | disease phenotypes: MIM:213000

GenCC curated gene-disease

Mondo (1): isolated cerebellar hypoplasia/agenesis (MONDO:0008939)

Orphanet (2): Isolated cerebellar agenesis (Orphanet:1398), Cerebellar hypoplasia-tapetoretinal degeneration syndrome (Orphanet:2246)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562568	Cerebellar Hypoplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, increases methylation, decreases reaction, increases abundance	4
Valproic Acid	increases methylation, affects expression, increases expression	4
(+)-JQ1 compound	increases expression	2
ginger extract	decreases reaction, increases abundance, increases expression	1
triphenyl phosphate	affects expression	1
tetrahydropalmatine	increases expression	1
K 7174	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Antimycin A	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Copper	affects binding, increases expression	1
Doxorubicin	affects expression	1
Ivermectin	decreases expression	1
Oils, Volatile	decreases reaction, increases abundance, increases expression	1
Ozone	increases abundance, affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Dronabinol	increases expression	1
Okadaic Acid	decreases expression	1
Genistein	increases reaction, decreases expression	1

Clinical trials (associated diseases)

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