PRAP1

Summary

PRAP1 (proline rich acidic protein 1, HGNC:23304) is a protein-coding gene on chromosome 10q26.3, encoding Proline-rich acidic protein 1 (Q96NZ9). Lipid-binding protein which promotes lipid absorption by facilitating MTTP-mediated lipid transfer (mainly triglycerides and phospholipids) and MTTP-mediated apoB lipoprotein assembly and secretion.

Predicted to enable triglyceride binding activity. Involved in DNA damage response, signal transduction by p53 class mediator; deactivation of mitotic spindle assembly checkpoint; and negative regulation of apoptotic process. Predicted to be located in endoplasmic reticulum and extracellular region.

Source: NCBI Gene 118471 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 28 total
• GTEx eGene: eQTL in 16 tissues, sQTL in 4 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.40 (unconstrained)
• MANE Select transcript: NM_145202

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23304
Approved symbol	PRAP1
Name	proline rich acidic protein 1
Location	10q26.3
Locus type	gene with protein product
Status	Approved
Aliases	UPA
Ensembl gene	ENSG00000165828
Ensembl biotype	protein_coding
OMIM	609776
Entrez	118471

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 16 protein_coding, 1 nonsense_mediated_decay

MANE Select: ENST00000433452

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2

ENST00000433452, ENST00000463201, ENST00000863040, ENST00000863041, ENST00000863042, ENST00000863043, ENST00000863044, ENST00001005480, ENST00001005481, ENST00001005482, ENST00001005483, ENST00001005484, ENST00001005485, ENST00001005486, ENST00001005487, ENST00001093979, ENST00001139252

RefSeq mRNA: 2 — MANE Select: NM_145202 NM_001145201, NM_145202

CCDS: CCDS44498, CCDS7679

Canonical transcript exons

ENST00000433452 — 5 exons

Exon	Start	End
ENSE00001185450	133352247	133352683
ENSE00001893257	133347373	133347425
ENSE00003791960	133350095	133350161
ENSE00003797617	133352007	133352140
ENSE00003800860	133351381	133351433

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 99.70.

FANTOM5 (CAGE): breadth broad, TPM avg 4.8619 / max 1517.2837, expressed in 230 samples.

Highest expression (Bgee): duodenum, lobe of liver, liver, mucosa of transverse colon, adult mammalian kidney.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRAP1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

20 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	1.3e-27	-2.34	10:133358728:G:A
Nerve Tibial	eqtl	3.0e-26	-0.72	10:133358288:T:C
Liver	sqtl	5.0e-22	+3.01	10:133361226:C:T
Testis	eqtl	3.9e-15	+0.44	10:133319668:C:T
Brain Cortex	eqtl	2.3e-07	+0.46	10:133315673:A:C
Small Intestine Terminal Ileum	sqtl	5.5e-06	-1.70	10:133336528:C:T
Colon Transverse	sqtl	2.1e-05	-1.13	10:133336528:C:T
Colon Transverse	eqtl	1.3e-04	+0.25	10:133384411:C:T
Brain Caudate basal ganglia	eqtl	2.3e-04	-0.75	10:133370917:C:G
Brain Frontal Cortex BA9	eqtl	3.3e-03	+1.25	10:132815472:G:A
Minor Salivary Gland	eqtl	3.3e-03	-1.10	10:133347676:C:T
Lung	eqtl	7.8e-03	-0.54	10:133370104:A:G
Colon Sigmoid	eqtl	1.0e-02	+0.47	10:133303243:AC:A
Esophagus Mucosa	eqtl	1.9e-02	-0.23	10:132794027:G:A
Small Intestine Terminal Ileum	eqtl	2.7e-02	+0.19	10:133377807:T:C
Pancreas	eqtl	2.9e-02	+1.16	10:132446580:G:A
Skin Sun Exposed Lower leg	eqtl	3.8e-02	+0.19	10:133412537:G:C
Brain Amygdala	eqtl	3.9e-02	+1.76	10:133271277:G:A
Brain Putamen basal ganglia	eqtl	4.2e-02	-0.69	10:133377956:T:G
Brain Cerebellum	eqtl	4.4e-02	-0.48	10:133344451:G:A

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
107791	4.0799	205
107790	0.7820	95

Top tissues by expression

showing 100 of 133 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	99.70	gold quality
right lobe of liver	UBERON:0001114	99.27	gold quality
liver	UBERON:0002107	98.95	gold quality
mucosa of transverse colon	UBERON:0004991	97.73	gold quality
adult mammalian kidney	UBERON:0000082	95.32	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.53	gold quality
small intestine	UBERON:0002108	94.09	gold quality
rectum	UBERON:0001052	89.10	gold quality
transverse colon	UBERON:0001157	87.55	gold quality
kidney	UBERON:0002113	87.12	gold quality
right testis	UBERON:0004534	83.56	gold quality
left testis	UBERON:0004533	82.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.23	silver quality
testis	UBERON:0000473	81.63	gold quality
tibial nerve	UBERON:0001323	81.52	gold quality
intestine	UBERON:0000160	79.98	gold quality
cortex of kidney	UBERON:0001225	77.16	gold quality
colon	UBERON:0001155	74.85	gold quality
metanephros cortex	UBERON:0010533	73.79	gold quality
vermiform appendix	UBERON:0001154	69.90	gold quality
gall bladder	UBERON:0002110	67.68	gold quality
colonic epithelium	UBERON:0000397	64.83	silver quality
monocyte	CL:0000576	64.30	gold quality
right uterine tube	UBERON:0001302	63.78	gold quality
smooth muscle tissue	UBERON:0001135	63.60	gold quality
mucosa of stomach	UBERON:0001199	63.42	gold quality
leukocyte	CL:0000738	62.41	gold quality
ovary	UBERON:0000992	61.08	gold quality
granulocyte	CL:0000094	61.02	gold quality
right ovary	UBERON:0002118	60.96	gold quality
left ovary	UBERON:0002119	60.93	gold quality
right frontal lobe	UBERON:0002810	60.50	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	58.99	gold quality
fallopian tube	UBERON:0003889	58.97	gold quality
left coronary artery	UBERON:0001626	58.05	gold quality
spleen	UBERON:0002106	57.99	gold quality
muscle layer of sigmoid colon	UBERON:0035805	57.88	gold quality
pituitary gland	UBERON:0000007	57.77	gold quality
Brodmann (1909) area 9	UBERON:0013540	57.66	gold quality
right coronary artery	UBERON:0001625	57.62	gold quality
frontal cortex	UBERON:0001870	57.45	gold quality
lymph node	UBERON:0000029	57.26	gold quality
fundus of stomach	UBERON:0001160	57.01	gold quality
left uterine tube	UBERON:0001303	56.18	gold quality
prefrontal cortex	UBERON:0000451	55.70	gold quality
cerebral cortex	UBERON:0000956	55.67	gold quality
thoracic mammary gland	UBERON:0005200	55.60	gold quality
subcutaneous adipose tissue	UBERON:0002190	55.50	gold quality
saliva-secreting gland	UBERON:0001044	55.48	gold quality
multicellular organism	UBERON:0000468	55.43	gold quality
right lung	UBERON:0002167	55.26	gold quality
adenohypophysis	UBERON:0002196	54.98	gold quality
ascending aorta	UBERON:0001496	54.97	gold quality
superior frontal gyrus	UBERON:0002661	54.96	gold quality
minor salivary gland	UBERON:0001830	54.68	gold quality
thoracic aorta	UBERON:0001515	54.22	gold quality
right hemisphere of cerebellum	UBERON:0014890	53.50	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	53.48	gold quality
adipose tissue	UBERON:0001013	53.47	gold quality
ventricular zone	UBERON:0003053	53.39	gold quality
vagina	UBERON:0000996	53.34	gold quality
urinary bladder	UBERON:0001255	53.14	gold quality
endocervix	UBERON:0000458	52.83	gold quality
bone marrow cell	CL:0002092	52.82	gold quality
temporal lobe	UBERON:0001871	52.71	gold quality
skin of abdomen	UBERON:0001416	52.60	gold quality
zone of skin	UBERON:0000014	52.53	gold quality
tonsil	UBERON:0002372	52.50	gold quality
amygdala	UBERON:0001876	52.47	gold quality
skin of leg	UBERON:0001511	52.45	gold quality
lower esophagus muscularis layer	UBERON:0035833	52.22	gold quality
blood	UBERON:0000178	52.17	gold quality
anterior cingulate cortex	UBERON:0009835	52.08	gold quality
lower esophagus	UBERON:0013473	52.00	gold quality
adrenal tissue	UBERON:0018303	51.93	gold quality
body of uterus	UBERON:0009853	51.65	gold quality
brain	UBERON:0000955	51.55	gold quality
uterine cervix	UBERON:0000002	51.54	gold quality
tibial artery	UBERON:0007610	51.29	gold quality
popliteal artery	UBERON:0002250	51.25	gold quality
cerebellar hemisphere	UBERON:0002245	51.12	gold quality
cerebellar cortex	UBERON:0002129	51.05	gold quality
stomach	UBERON:0000945	51.00	gold quality
cerebellum	UBERON:0002037	50.91	gold quality
descending thoracic aorta	UBERON:0002345	50.88	gold quality
Ammon’s horn	UBERON:0001954	50.65	gold quality
omental fat pad	UBERON:0010414	50.61	gold quality
prostate gland	UBERON:0002367	50.59	gold quality
ectocervix	UBERON:0012249	50.40	gold quality
body of stomach	UBERON:0001161	50.05	gold quality
esophagus	UBERON:0001043	49.11	gold quality
bone marrow	UBERON:0002371	48.58	gold quality
muscle tissue	UBERON:0002385	48.53	gold quality
upper lobe of left lung	UBERON:0008952	48.53	gold quality
heart left ventricle	UBERON:0002084	48.52	gold quality
heart	UBERON:0000948	48.41	gold quality
right atrium auricular region	UBERON:0006631	48.06	gold quality
caudate nucleus	UBERON:0001873	48.01	gold quality
left lobe of thyroid gland	UBERON:0001120	47.50	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	46.96	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	12140.97
E-CURD-46	yes	8356.12
E-CURD-122	yes	3765.02
E-MTAB-9906	yes	2259.23
E-MTAB-8410	yes	1370.22
E-CURD-98	yes	917.48
E-HCAD-9	yes	55.94
E-ANND-3	yes	24.04
E-MTAB-3929	no	330.40
E-MTAB-6379	no	1.34

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 74 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Small intestine	tissue	1069.3	high
Duodenum	tissue	991.0	medium
Liver	tissue	630.5	medium
Kidney	tissue	135.5	medium
Colon	tissue	69.9	not detected
Rectum	tissue	33.4
Choroid plexus	tissue	16.1
Testis	tissue	6.6	not detected
Cerebellum	tissue	4.1	not detected
Basal ganglia	tissue	4.0	not detected
Appendix	tissue	3.9	medium
Locus coeruleus	tissue	3.3
Putamen	tissue	3.1
Ventral forebrain	tissue	3.0
Hippocampus	tissue	2.9	not detected
Stomach 1	tissue	2.7	not detected
Cerebral cortex	tissue	2.7	not detected
Somatosensory cortex	tissue	2.7
Nucleus accumbens	tissue	2.6
Postcentral gyrus	tissue	2.6
Gallbladder	tissue	2.5	not detected
Motor cortex	tissue	2.4
Retrosplenial cortex	tissue	2.4
Hippocampal formation	tissue	2.3
Insular cortex	tissue	2.3
Prefrontal cortex	tissue	2.2
Amygdala	tissue	2.2
Occipital cortex	tissue	2.2
Entorhinal cortex	tissue	2.1
Thalamus	tissue	1.9
Retrosplenial and cingulate cortex	tissue	1.9
Septum	tissue	1.9
Temporal cortex	tissue	1.9
Medulla oblongata	tissue	1.7
Salivary gland	tissue	1.6	not detected
Smooth muscle	tissue	1.6	not detected
Hypothalamus	tissue	1.6
Lymph node	tissue	1.4	not detected
Pons	tissue	1.4
Skin 1	tissue	1.3	not detected
Midbrain	tissue	1.3
Corpus callosum	tissue	1.3
Superior colliculi	tissue	1.2
Substantia nigra	tissue	1.2
Periaqueductal gray	tissue	1.2
Olfactory bulb	tissue	1.2
Pituitary gland	tissue	1.0
Endometrium 1	tissue	0.8	not detected
Spinal cord	tissue	0.8
Spleen	tissue	0.7	not detected
Fallopian tube	tissue	0.7	not detected
Adipose tissue	tissue	0.6	not detected
Bone marrow	tissue	0.6	not detected
Heart muscle	tissue	0.4	not detected
Esophagus	tissue	0.4	not detected
Adrenal gland	tissue	0.4	not detected
Ovary	tissue	0.3	not detected
Seminal vesicle	tissue	0.3	not detected
Tongue	tissue	0.3
Thymus	tissue	0.3

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Nucleus ambiguus (4.9), Principal sensory trigeminal nucleus (4.8), Motor trigeminal nucleus (4.5), Lateral vestibular nucleus (4.4), Nucleus gracilis (4.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

Targeting PRAP1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

8 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-193B-5P	97.91	65.88	837
HSA-MIR-1234-3P	86.70	58.45	109
HSA-MIR-7107-5P	86.70	59.28	110

Functional genomics

gnomAD constraint: pLI 1.36e-05, LOEUF 1.4, missense Z 1.04 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000433452 — one region, missense o/e 0.83.

Literature-anchored findings (GeneRIF, showing 4)

• Induction of PRAP1 expression by p53 in response to DNA-damaging agents contributes to cancer cell survival. (PMID:23235459)
• PRAP1 is a protein interacting partner of MAD1 and that PRAP1 is able to down-regulate MAD1 and suppress mitotic checkpoint signalling in hepatocellular carcinoma. (PMID:24374861)
• ATF3 and PRAP1 play important roles in cisplatin-induced DNA damage repair process. (PMID:29886035)
• Proline-Rich Acidic Protein 1 (PRAP1) Protects the Gastrointestinal Epithelium From Irradiation-Induced Apoptosis. (PMID:32629119)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prap1	ENSMUSG00000025467
rattus_norvegicus	Prap1	ENSRNOG00000018446

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:893573) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 14 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal humoral immune response	1
increased inflammatory response	1
increased immunoglobulin level	1
abnormal cell cycle	1
increased mortality induced by ionizing radiation	1
increased cellular sensitivity to ionizing radiation induced cell death	1
increased circulating interleukin-2 level	1
increased circulating interleukin-4 level	1
increased circulating interleukin-12 level	1
increased interleukin-12b secretion	1
abnormal enterocyte physiology	1
increased enterocyte apoptosis	1
abnormal gut flora balance	1
abnormal response to radiation	1

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ZNF511-PRAP1	protein-coding	104326056
ECHS1	protein-coding	1892
PAOX	protein-coding	196743
FUOM	protein-coding	282969
MIR3944	ncRNA	100500911
ADAM8	protein-coding	101
TUBGCP2	protein-coding	10844
ZNF511	protein-coding	118472
CALY	protein-coding	50632

Protein

Protein identifiers

Proline-rich acidic protein 1 — Q96NZ9 (reviewed: Q96NZ9)

Alternative names: Epididymis tissue protein Li 178, Uterine-specific proline-rich acidic protein

All UniProt accessions (2): A6XND8, Q96NZ9

UniProt curated annotations — full annotation on UniProt →

Function. Lipid-binding protein which promotes lipid absorption by facilitating MTTP-mediated lipid transfer (mainly triglycerides and phospholipids) and MTTP-mediated apoB lipoprotein assembly and secretion. Protects the gastrointestinal epithelium from irradiation-induced apoptosis. May play an important role in maintaining normal growth homeostasis in epithelial cells. Involved in p53/TP53-dependent cell survival after DNA damage. May down-regulate the expression of MAD1L1 and exert a suppressive role in mitotic spindle assembly checkpoint in hepatocellular carcinomas.

Subunit / interactions. Interacts with isoform 1 and isoform 3 of MAD1L1. Interacts with MTTP.

Subcellular location. Secreted. Endoplasmic reticulum.

Tissue specificity. Highly expressed in the intestinal epithelial cells (at protein level). Abundantly expressed in the epithelial cells of the liver, kidney and cervix. Significantly down-regulated in hepatocellular carcinoma and right colon adenocarcinoma compared with the respective adjacent normal tissues. Expressed in epididymis (at protein level).

Induction. Up-regulated by butyrate, trichostatin A and 5’-aza-2’ deoxycytidine. Induced by DNA-damaging agents in a p53/TP53-dependent manner in HepG2 liver cancer cell line and HCT116 colon cancer cell line.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96NZ9-1	1, PRAP	yes
Q96NZ9-2	2
Q96NZ9-3	3, PRAPV1
Q96NZ9-4	4, PRAPV2

RefSeq proteins (2): NP_001138673, NP_660203* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027922	PRAP	Family

Pfam: PF15314

UniProt features (10 total): sequence variant 4, splice variant 3, signal peptide 1, chain 1, region of interest 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NZ9-F1	61.73	0.02

Human Protein Atlas

Protein class: Predicted secreted proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH supported

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 138 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_DIGESTION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_CHROMOSOME_SEPARATION, GOBP_POSITIVE_REGULATION_OF_DIGESTIVE_SYSTEM_PROCESS, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_LIPID_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT

GO Biological Process (8): DNA damage response (GO:0006974), DNA damage response, signal transduction by p53 class mediator (GO:0030330), negative regulation of apoptotic process (GO:0043066), cellular response to X-ray (GO:0071481), deactivation of mitotic spindle assembly checkpoint (GO:1902426), positive regulation of intestinal lipid absorption (GO:1904731), positive regulation of triglyceride transport (GO:1905885), positive regulation of phospholipid transport (GO:2001140)

GO Molecular Function (3): triglyceride binding (GO:0017129), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (2): extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783)

GO top-level categories

24 GO namespaces:

Category	Terms
binding	2
cellular response to stress	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
response to X-ray	1
cellular response to ionizing radiation	1
negative regulation of mitotic spindle assembly checkpoint signaling	1
intestinal lipid absorption	1
positive regulation of intestinal absorption	1
regulation of intestinal lipid absorption	1
triglyceride transport	1
positive regulation of acylglycerol transport	1
regulation of triglyceride transport	1
phospholipid transport	1
positive regulation of lipid transport	1
regulation of phospholipid transport	1
lipid binding	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
DNA damage response	BP	direct assay
DNA damage response, signal transduction by p53 class mediator	BP	mutant phenotype
deactivation of mitotic spindle assembly checkpoint	BP	direct assay
negative regulation of apoptotic process	BP	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 272 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRAP1	RPP40	O75818	469
PRAP1	LZTS3	O60299	450
PRAP1	TMEM184B	Q9Y519	444
PRAP1	RTP3	Q9BQQ7	392
PRAP1	DNPH1	O43598	382
PRAP1	ANHX	E9PGG2	372
PRAP1	TP53TG5	Q9Y2B4	370
PRAP1	RPL37A	P12751	370
PRAP1	NPL	Q9BXD5	359
PRAP1	FUOM	A2VDF0	350
PRAP1	WFDC2	Q14508	350
PRAP1	SYNGR4	O95473	328
PRAP1	PRR30	Q53SZ7	325
PRAP1	MTTP	P55157	318
PRAP1	PLEKHD1	A6NEE1	311

IntAct

Human interaction partners of PRAP1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

15 partners by confidence:

Partner	Interaction type	MIscore	Records
SGTA	physical association	0.720	9
UBQLN1	physical association	0.720	9
UBQLN2	physical association	0.560	6
AHNAK2	physical association	0.560	3
ASPH	physical association	0.560	3
CEP19	physical association	0.560	3
HSPA6	physical association	0.560	3
MEOX2	physical association	0.560	3
MRFAP1	physical association	0.560	3
SGTB	physical association	0.560	3
CD48	association	0.530	1
HSPA5	physical association	0.400	1
MEP1B	physical association	0.370	1
IGHA1	association	0.350	1
GRB2	physical association	0.000	1

BioGRID (26 interactions; top human partners by supporting records): CD48 (Affinity Capture-MS; 3 records), LACRT (Affinity Capture-MS; 3 records), UBQLN1 (Two-hybrid; 3 records), IGHA1 (Affinity Capture-MS; 2 records), SGTA (Two-hybrid; 2 records), AHNAK2 (Two-hybrid), ASPH (Two-hybrid), CEP19 (Two-hybrid), GRB2 (Two-hybrid), HSPA5 (Affinity Capture-MS), HSPA6 (Two-hybrid), LTF (Affinity Capture-MS), MEOX2 (Two-hybrid), MRFAP1 (Two-hybrid), POLI (Reconstituted Complex)

Disease & clinical

Genetic variants

Variant evidence for PRAP1: 28 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 311):

Position(s)	Effect	Δscore	Sites
10:133352245–133352246	acceptor_loss	1.0000	4
10:133347427	donor_loss	0.9900
10:133350093–133350094	acceptor_loss	0.9900	6
10:133350162–133350163	donor_loss	0.9900	5
10:133352238	acceptor_gain	0.9900
10:133352245	acceptor_loss	0.9900
10:133347426–133347427	donor_loss	0.9800	3
10:133352005–133352006	acceptor_loss	0.9800	6
10:133352114–133352115	donor_loss	0.9800	6
10:133350163	donor_loss	0.9700

AlphaMissense

74 missense substitutions predicted likely pathogenic (of 981 scored), across 21 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D145	8	0.877	0.936
D143	8	0.835	0.911
D110	7	0.797	0.858
H149	7	0.790	0.907
D108	7	0.667	0.731
H114	5	0.749	0.841
E141	5	0.713	0.827
G139	4	0.763	0.825
S9	3	0.931	0.931
I147	3	0.693	0.739
S104	3	0.663	0.663
E106	3	0.627	0.648
H146	2	0.603	0.603
W129	2	0.601	0.601
V7	1	0.671	0.671
D97	1	0.621	0.621
V12	1	0.602	0.602
V11	1	0.598	0.598
L10	1	0.582	0.582
P140	1	0.581	0.581

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Disease associations

OMIM: gene MIM:609776 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST007250_1	Nonunion in individuals with fractures	2e-8

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0009707	fractures, ununited

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4879502 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 421 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL4098253	AZD2461	1	421

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

6 measured of 6 human assays (6 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4856941	KD	0.0203 nM
CHEMBL4849327	KD	0.043 nM
CHEMBL4850135	KD	0.0916 nM
CHEMBL4869660	KD	0.112 nM
CHEMBL4098253	IC50	1.7 nM
CHEMBL4854774	IC50	37 nM

ChEMBL bioactivities

6 potent at pChembl≥5 of 6 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.16	IC50	6.87	nM	CHEMBL4854774
8.15	IC50	7.09	nM	AZD2461
8.08	IC50	8.35	nM	CHEMBL4850135
7.87	IC50	13.56	nM	CHEMBL4856941
7.82	IC50	15.28	nM	CHEMBL4869660
7.72	IC50	19.09	nM	CHEMBL4849327

PubChem BioAssay actives

6 with measured affinity, of 6 total; 6 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-acetamido-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-5-[6-[4-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperazin-1-yl]-3-pyridinyl]-2-methylbenzamide	1773629: Inhibition of PRAP1 (unknown origin) by HT universal chemiluminescent assay	ic50	0.0069	uM
4-[[4-fluoro-3-(4-methoxypiperidine-1-carbonyl)phenyl]methyl]-2H-phthalazin-1-one	1773629: Inhibition of PRAP1 (unknown origin) by HT universal chemiluminescent assay	ic50	0.0071	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-5-[6-[4-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperazin-1-yl]-3-pyridinyl]-2-methyl-3-(propanoylamino)benzamide	1773629: Inhibition of PRAP1 (unknown origin) by HT universal chemiluminescent assay	ic50	0.0083	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-[ethyl(propanoyl)amino]-5-[6-[4-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperazin-1-yl]-3-pyridinyl]-2-methylbenzamide	1773629: Inhibition of PRAP1 (unknown origin) by HT universal chemiluminescent assay	ic50	0.0136	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-5-[6-[4-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperazin-1-yl]-3-pyridinyl]-2-methyl-3-(3-methylbutanoylamino)benzamide	1773629: Inhibition of PRAP1 (unknown origin) by HT universal chemiluminescent assay	ic50	0.0153	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-[ethyl(2-methylprop-2-enoyl)amino]-5-[6-[4-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperazin-1-yl]-3-pyridinyl]-2-methylbenzamide	1773629: Inhibition of PRAP1 (unknown origin) by HT universal chemiluminescent assay	ic50	0.0191	uM

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	4
Aflatoxin B1	increases expression, affects expression, decreases expression	3
sodium arsenite	decreases expression, increases expression, decreases reaction, increases secretion	2
Valproic Acid	affects expression, decreases expression	2
tris(2-butoxyethyl) phosphate	affects expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects methylation, affects cotreatment, decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4833010	Binding	Inhibition of PRAP1 (unknown origin) by HT universal chemiluminescent assay	Discovery of First-in-Class Dual PARP and EZH2 Inhibitors for Triple-Negative Breast Cancer with Wild-Type BRCA. — *J Med Chem*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2C1	Abcam HeLa PRAP1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PRAP1 across ~30M SureChEMBL compounds — explore on Sugi Predict.