PELP1

Summary

PELP1 (proline, glutamate and leucine rich protein 1, HGNC:30134) is a protein-coding gene on chromosome 17p13.2, encoding Proline-, glutamic acid- and leucine-rich protein 1 (Q8IZL8). Coactivator of estrogen receptor-mediated transcription and a corepressor of other nuclear hormone receptors and sequence-specific transcription factors. It is a common-essential gene (DepMap: required in 96.6% of cancer cell lines).

This gene encodes a transcription factor which coactivates transcription of estrogen receptor responsive genes and corepresses genes activated by other hormone receptors or sequence-specific transcription factors. Expression of this gene is regulated by both members of the estrogen receptor family. This gene may be involved in the progression of several types of cancer. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 27043 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 72 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 96.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_014389

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30134
Approved symbol	PELP1
Name	proline, glutamate and leucine rich protein 1
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	MNAR
Ensembl gene	ENSG00000141456
Ensembl biotype	protein_coding
OMIM	609455
Entrez	27043

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 15 protein_coding, 6 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000301396, ENST00000436683, ENST00000570387, ENST00000570571, ENST00000570823, ENST00000571170, ENST00000571347, ENST00000572293, ENST00000573242, ENST00000573506, ENST00000573523, ENST00000574876, ENST00000575101, ENST00000575329, ENST00000575534, ENST00000897361, ENST00000897362, ENST00000924580, ENST00000924581, ENST00000924582, ENST00000924583, ENST00000960490, ENST00000960491

RefSeq mRNA: 2 — MANE Select: NM_014389 NM_001278241, NM_014389

CCDS: CCDS58503, CCDS62038

Canonical transcript exons

ENST00000572293 — 17 exons

Exon	Start	End
ENSE00002634587	4703863	4704137
ENSE00003476735	4682803	4682952
ENSE00003509520	4673250	4673456
ENSE00003542473	4671691	4673145
ENSE00003547497	4682502	4682573
ENSE00003561168	4674510	4674669
ENSE00003569480	4673619	4673674
ENSE00003595305	4676036	4676162
ENSE00003601616	4691378	4691442
ENSE00003631382	4674809	4674956
ENSE00003633506	4675274	4675362
ENSE00003641713	4676357	4676507
ENSE00003644127	4690888	4690993
ENSE00003660612	4675797	4675884
ENSE00003676872	4675079	4675195
ENSE00003684886	4676753	4676812
ENSE00003762388	4669774	4671531

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 97.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.6647 / max 110.1213, expressed in 1781 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163931	17.6594	1781
163929	0.0053	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	97.19	gold quality
sural nerve	UBERON:0015488	94.68	gold quality
mucosa of stomach	UBERON:0001199	93.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.57	gold quality
cerebellar hemisphere	UBERON:0002245	93.34	gold quality
left testis	UBERON:0004533	93.27	gold quality
cerebellar cortex	UBERON:0002129	93.25	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.05	gold quality
apex of heart	UBERON:0002098	93.03	gold quality
right uterine tube	UBERON:0001302	93.01	gold quality
right testis	UBERON:0004534	92.90	gold quality
adenohypophysis	UBERON:0002196	92.67	gold quality
gastrocnemius	UBERON:0001388	92.40	gold quality
cerebellum	UBERON:0002037	92.35	gold quality
right frontal lobe	UBERON:0002810	92.24	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.21	gold quality
pituitary gland	UBERON:0000007	92.19	gold quality
medial globus pallidus	UBERON:0002477	92.00	gold quality
left ovary	UBERON:0002119	91.76	gold quality
right ovary	UBERON:0002118	91.75	gold quality
amygdala	UBERON:0001876	91.59	gold quality
muscle of leg	UBERON:0001383	91.57	gold quality
body of uterus	UBERON:0009853	91.49	gold quality
spinal cord	UBERON:0002240	91.33	gold quality
globus pallidus	UBERON:0001875	91.21	gold quality
putamen	UBERON:0001874	91.15	gold quality
right lobe of thyroid gland	UBERON:0001119	91.11	gold quality
left uterine tube	UBERON:0001303	91.10	gold quality
nucleus accumbens	UBERON:0001882	91.08	gold quality
lower esophagus mucosa	UBERON:0035834	90.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.89

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
NR3C1	Activation

Upstream regulators (CollecTRI, top): AP1, DACH1, ESR1, ESR2, NFKB, NR4A1

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• PELP1 is a coactivator of estrogen receptor (ER), interacts with ER, and may have a role in mammary tumorigenesis. (PMID:11481323)
• PELP1, a steroid coactivator, plays a permissive role in E2-mediated cell cycle progression, presumably via its regulatory interaction with the pRb pathway (PMID:12682072)
• Results provide novel insights about the transcription regulation of PELP1 and suggest that PELP1 participates in chromatin remodeling activity via displacement of histone 1 in cancer cells. (PMID:15374949)
• PELP1 recruits HDAC2 and masks histones using two separate domains (PMID:15456770)
• PELP1 expression and localization are widely deregulated in endometrial cancers. PELP1 and ERbeta were localized predominantly in cytoplasm of high-grade endometrial tumors. PELP1 may play essential role in proliferation of cancerous endometrial cells. (PMID:15579769)
• PELP1 / MNAR and estrogen receptor beta are coexpressed in most salivary duct carcinoma and may play a role in the pathobiology of these tumors. (PMID:16021574)
• Results suggest that the altered localization of PELP1 modulates sensitivity to antiestrogens, potentiates tumorigenicity via the activation of MAPK and AKT, and enhances cross-regulation of ER transactivation activity by growth factors. (PMID:16140940)
• Presence of MNAR in the cell nucleus indicates that it may play a role in regulation of gene expression. (PMID:16297421)
• role of HRS in up-regulating MAPK, presumably involving interaction with PELP1. (PMID:16352611)
• PELP1/MNAR increases estradiol-mediated cell proliferation and participates in estradiol mediated tumorigenesis and metastasis. [REVIEW] (PMID:16826428)
• PELP1/MNAR may contribute to the tumorigenic potential of cancer cells by serving as a scaffolding protein that couples various signaling complexes with Estrogen Receptors (review) (PMID:17128415)
• PELP1 functions as a molecular adaptor, coupling FHL2 with nuclear receptors, and PELP1-FHL2 interactions may have a role in prostate cancer progression. (PMID:17192406)
• Data suggest that PELP1 is a potential oncogene, that its expression is deregulated during cancer progression, and that PELP1 may play a role in oncogenesis. (PMID:17545633)
• PELP1 and HRS reallocate to autophagosomes in response to resveratrol treatment, which might be important in the process of autophagy in the cancer cells. (PMID:17804729)
• PELP1 signaling and its interactions with growth factor signaling components and orphan nuclear reactors may locally influence production of estradiol and promote tumor growth by promoting estrogen receptor autocrine signaling. (PMID:18079323)
• MNAR plays an important role in ERa activation of Src/MAPK and PI3K/Akt signaling pathways [review] (PMID:18261753)
• growth factor signals promote phosphorylation of ER coactivator PELP1 via PKA pathway, and such modification may have functional implications in breast tumors with deregulated growth factor signaling (PMID:18505929)
• Overexpression of PELP1 is associated with ovarian tumorigenesis (PMID:18559538)
• MNAR interacts with glucocorticoid receptor(GR) in the nucleus but not cytoplasm and regulates GR transactivation in a complex manner depending on cell type. MNAR is capable of regulating both AF1 and AF2 functions of the GR independently. (PMID:18682536)
• Statistical analysis revealed an increase in PELP1 expression in myofibroblasts from normal mucosa through adenomas to colorectal carcinomas. (PMID:19048289)
• ERalpha is rarely expressed while ERbeta and PELP1/MNAR are involved in colorectal tumorigenesis. (PMID:19478391)
• PELP1 protein expression is an independent prognostic predictor of shorter breast-cancer-specific survival and disease-free interval in breast cancer. Its elevated expression is positively associated with markers of poor outcome. (PMID:19495959)
• PELP1 regulation of aromatase P450 (Cyp19), represent a novel mechanism for in situ estrogen synthesis leading to tumor proliferation by autocrine loop and open a new avenue for ablating local aromatase activity in breast tumors. (PMID:19800002)
• These results suggest that PELP1 is a reader of H3 methylation marks and has a crucial role in modulating the histone code at the ERalpha target genes. (PMID:20448663)
• These data define the PELP1-TEX10-WDR18 complex as a regulator of ribosome biogenesis and suggests that its SUMO-controlled distribution coordinates the rate of ribosome formation. (PMID:21326211)
• Results suggest that PELP1 signaling axis is a potential druggable target and liposomal PELP1-siRNA-DOPC could be used as a novel drug to prevent or treat ovarian metastasis. (PMID:21421858)
• proto-oncogene PELP1 plays a vital role in rDNA transcription (PMID:21695158)
• Univariate survival analysis revealed that high PELP1 expression was associated with worse prognosis in astrocytic brain tumors (PMID:21735116)
• PELP1 may be a potential therapeutic target for metastatic ER-negative breast cancer. (PMID:22086908)
• PELP1 may enable estradiol-induced androgen receptor (AR) signaling by forming a protein complex between AR, estrogen receptor beta, and PELP1 on the DNA, leading to the proliferation of prostate cancer cells in the absence of androgen. (PMID:22403175)
• Recruitment of the protein complex 5FMC to Zbp-89, a zinc-finger transcription factor, affects its sumoylation status and transactivation potential.[5FMC] (PMID:22872859)
• results suggest that PELP1/MNAR plays a role in endometrial cancer progression and metastasis (PMID:22992812)
• Inhibition of CARM1 decreases PELP1 oncogenic activity. (PMID:23486015)
• PELP1 regulates tumor metastasis by controlling the expression and functions of the tumor metastasis suppressors miR-200a and miR-141 (PMID:23975430)
• PELP1 oncogenic functions involve alternative splicing via PRMT6. (PMID:24447537)
• unliganded PR-B enhanced proliferative responses to estradiol and IGF1 via scaffolding of ER-alpha/PELP1/IGF1R-containing complexes (PMID:24469035)
• Overexpression of PELP1 in Chinese women with primary breast cancer appears to be associated with biomarkers of poor outcome; these results are similar to other reports based on Western populations. (PMID:24627205)
• our data identified the PELP1-mTOR axis as a novel component of PELP1 oncogenic functions and suggest that mTOR inhibitor(s) will be effective chemotherapeutic agents for downregulating PELP1 oncogenic functions. (PMID:24688046)
• MacroH2A1 specifically recruits PELP1 to the promoters of macroH2A1 target genes, but macroH2A1 occupancy occurs independent of PELP1. This recruitment allows macroH2A1 and PELP1 to cooperatively regulate gene expression outcomes. (PMID:24752897)
• The PELP1 interacts with p53, functions as p53-coactivator and is required for optimal activation of p53 target genes under genomic stress. (PMID:24786831)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pelp1	ENSMUSG00000018921
rattus_norvegicus	Pelp1	ENSRNOG00000019268

Protein

Protein identifiers

Proline-, glutamic acid- and leucine-rich protein 1 — Q8IZL8 (reviewed: Q8IZL8)

Alternative names: Modulator of non-genomic activity of estrogen receptor, Transcription factor HMX3

All UniProt accessions (7): C9JFV4, E7EV54, I3L1P4, I3L445, I3L4M7, I3L4P1, Q8IZL8

UniProt curated annotations — full annotation on UniProt →

Function. Coactivator of estrogen receptor-mediated transcription and a corepressor of other nuclear hormone receptors and sequence-specific transcription factors. Plays a role in estrogen receptor (ER) genomic activity when present in the nuclear compartment by activating the ER target genes in a hormonal stimulation dependent manner. Can facilitate ER non-genomic signaling via SRC and PI3K interaction in the cytosol. Plays a role in E2-mediated cell cycle progression by interacting with RB1. May have important functional implications in ER/growth factor cross-talk. Interacts with several growth factor signaling components including EGFR and HRS. Functions as the key stabilizing component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit. Regulates pre-60S association of the critical remodeling factor MDN1. May promote tumorigenesis via its interaction with and modulation of several oncogenes including SRC, PI3K, STAT3 and EGFR. Plays a role in cancer cell metastasis via its ability to modulate E2-mediated cytoskeleton changes and cell migration via its interaction with SRC and PI3K.

Subunit / interactions. Interacts with HRS, RXRA, SUMO2, HDAC2, RB1 and STAT3. Interacts with PI3K, SRC and EGFR in cytoplasm. Interacts with ESR1, the interaction is enhanced by 17-beta-; the interaction increases ESR1 transcriptional activity. Interacts with CREBBP and EP300 in a ligand-dependent manner. Forms two complexes in the presence of 17-beta-estradiol; one with SRC (via the SH3 domain) and ESR1 and another with LCK and ESR1. Interacts with histone H1 and H3 with a greater affinity for H1. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BACC1, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Core component of the 5FMC complex, at least composed of PELP1, LAS1L, TEX10, WDR18 and SENP3; the complex interacts with methylated CHTOP and ZNF148. Interacts with NOL9. Interacts with BCAS3. Component of the PELP1 complex, composed of at least PELP1, TEX10 and WDR18. The complex interacts (via PELP1) with MDN1 (via its hexameric AAA ATPase ring) and the pre-60S ribosome particles.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm. Cytoplasm.

Tissue specificity. Widely expressed.

Post-translational modifications. Transiently sumoylated, preferentially conjugated to SUMO2 or SUMO3. Sumoylation causes nucleolar exclusion of PELP1 and promotes the recruitment of MDN1 to pre-60S particles. Desumoylation by SUMO isopeptidase SENP3 is needed to release both PELP1 and MDN1 from pre-ribosomes.

Domain organisation. The Glu-rich region mediates histones interaction. The Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are required for the association with nuclear receptor ESR1.

Miscellaneous. Expression is increased in breast tumor samples.

Similarity. Belongs to the RIX1/PELP1 family.

RefSeq proteins (2): NP_001265170, NP_055204* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR012583	RIX1_N	Domain
IPR012980	PELP1_middle	Domain
IPR016024	ARM-type_fold	Homologous_superfamily

Pfam: PF08166, PF08167

UniProt features (72 total): helix 29, short sequence motif 11, compositionally biased region 9, modified residue 8, region of interest 4, strand 3, turn 2, initiator methionine 1, chain 1, cross-link 1, sequence variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8FL3	ELECTRON MICROSCOPY	2.53
9DUO	ELECTRON MICROSCOPY	2.66
8FL2	ELECTRON MICROSCOPY	2.67
7UWF	ELECTRON MICROSCOPY	2.7
8FL4	ELECTRON MICROSCOPY	2.89
9ME8	X-RAY DIFFRACTION	2.93
9DUM	ELECTRON MICROSCOPY	3.56

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZL8-F1	64.18	0.25

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 (9): 2, 13, 477, 481, 488, 745, 1033, 1043, 826

Mutagenesis-validated functional residues (1):

Position	Phenotype
826	not sumoylated.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-8849473	PTK6 Expression

MSigDB gene sets: 141 (showing top): GOBP_RIBOSOME_BIOGENESIS, WANG_CLIM2_TARGETS_UP, CMYB_01, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, PUJANA_CHEK2_PCC_NETWORK, MUELLER_PLURINET, E2F_Q3, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_MATURATION_OF_5_8S_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_MATURATION_OF_LSU_RRNA, GOBP_RESPONSE_TO_ESTROGEN, OCT1_06, GOBP_RESPONSE_TO_HORMONE, CREB_Q3

GO Biological Process (3): rRNA processing (GO:0006364), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to estrogen stimulus (GO:0071391)

GO Molecular Function (4): chromatin binding (GO:0003682), RNA binding (GO:0003723), SUMO binding (GO:0032183), protein binding (GO:0005515)

GO Cellular Component (7): euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), membrane (GO:0016020), MLL1 complex (GO:0071339)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1
Signaling by PTK6	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
nuclear lumen	2
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cellular response to hormone stimulus	1
response to estrogen	1
nucleic acid binding	1
ubiquitin-like protein binding	1
chromatin	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
MLL1/2 complex	1

Protein interactions and networks

STRING

1804 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PELP1	TEX10	Q9NXF1	983
PELP1	WDR18	Q9BV38	943
PELP1	ESR1	P03372	897
PELP1	LAS1L	Q9Y4W2	884
PELP1	SENP3	Q9H4L4	829
PELP1	ILK	P57043	736
PELP1	MTA1	Q13330	710
PELP1	ESR2	Q92731	673
PELP1	SRC	P12931	654
PELP1	NCOA3	Q9Y6Q9	628
PELP1	NCOA1	Q15788	577
PELP1	HDAC2	Q92769	557
PELP1	PGR	P06401	555
PELP1	KDM1A	O60341	547
PELP1	EGFR	P00533	543

IntAct

139 interactions, top by confidence:

A	B	Type	Score
WDR18	PELP1	psi-mi:“MI:0915”(physical association)	0.900
PELP1	WDR18	psi-mi:“MI:0914”(association)	0.900
PELP1	WDR18	psi-mi:“MI:0915”(physical association)	0.900
PELP1	WDR18	psi-mi:“MI:0407”(direct interaction)	0.900
PELP1	SENP3	psi-mi:“MI:0915”(physical association)	0.800
SENP3	PELP1	psi-mi:“MI:0915”(physical association)	0.800
PELP1	SENP3	psi-mi:“MI:0403”(colocalization)	0.800
SENP3	NPM1	psi-mi:“MI:0914”(association)	0.780
TEX10	PELP1	psi-mi:“MI:0915”(physical association)	0.720
BOP1	NPM1	psi-mi:“MI:0403”(colocalization)	0.710
NPM1	PELP1	psi-mi:“MI:0403”(colocalization)	0.660
PELP1	NPM1	psi-mi:“MI:0915”(physical association)	0.660
NPM1	PELP1	psi-mi:“MI:0915”(physical association)	0.660
PELP1	KDM1A	psi-mi:“MI:0915”(physical association)	0.630
KDM1A	PELP1	psi-mi:“MI:0915”(physical association)	0.630
PELP1	KDM1A	psi-mi:“MI:0914”(association)	0.630
KDM1A	PELP1	psi-mi:“MI:0407”(direct interaction)	0.630

BioGRID (312): PELP1 (Affinity Capture-MS), PELP1 (Affinity Capture-MS), PELP1 (Affinity Capture-MS), PELP1 (Reconstituted Complex), PELP1 (Affinity Capture-Western), BCAS3 (Affinity Capture-Western), PELP1 (Reconstituted Complex), BCAS3 (Reconstituted Complex), PELP1 (Affinity Capture-MS), PELP1 (Affinity Capture-MS), PELP1 (Affinity Capture-MS), PELP1 (Affinity Capture-MS), PELP1 (Affinity Capture-MS), PELP1 (Affinity Capture-MS), NOL9 (Co-fractionation)

ESM2 similar proteins: A0JN53, A1L3T7, C9JE40, D2I4M3, G3HQ82, O43299, O75800, O94812, P58660, Q0P5G1, Q15572, Q1RMI8, Q1W1Y5, Q3T1I9, Q3U829, Q56B11, Q571B6, Q58CQ5, Q5ND34, Q5R8S0, Q66H85, Q6NZL6, Q6ZNJ1, Q6ZQA0, Q76MJ5, Q80TE0, Q80UU1, Q80UW5, Q8BGI5, Q8BMG1, Q8C3R1, Q8C3S2, Q8C7B8, Q8CE13, Q8IZL8, Q8N163, Q8VDP4, Q8WXE1, Q96HA7, Q9BQG0

Diamond homologs: Q1W1Y5, Q56B11, Q58HI1, Q8IZL8, Q9DBD5

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CDK2	up-regulates	PELP1	phosphorylation
CDK4	up-regulates	PELP1	phosphorylation
PELP1	“up-regulates quantity by expression”	NR3C1	“transcriptional regulation”
MDN1	“up-regulates quantity by stabilization”	PELP1	binding
PELP1	“form complex”	“Rix1 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 123 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
rRNA processing in the nucleus and cytosol	8	14.3×	2e-05
rRNA processing	8	13.0×	3e-05
Major pathway of rRNA processing in the nucleolus and cytosol	17	11.7×	3e-11
SRP-dependent cotranslational protein targeting to membrane	9	10.0×	4e-05
Peptide chain elongation	7	9.9×	5e-04
Viral mRNA Translation	7	9.9×	5e-04
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	7	9.8×	5e-04
Influenza Infection	5	9.8×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal complex assembly	5	27.4×	2e-04
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	5	18.2×	1e-03
cytoplasmic translation	9	15.2×	6e-06
negative regulation of translation	7	12.5×	2e-04
rRNA processing	9	11.6×	3e-05
ribosomal small subunit biogenesis	5	10.3×	8e-03
translation	9	8.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2303 predictions. Top by Δscore:

Variant	Effect	Δscore
17:4673617:AC:A	donor_gain	1.0000
17:4673618:CC:C	donor_gain	1.0000
17:4673672:GGCC:G	acceptor_loss	1.0000
17:4673675:C:CC	acceptor_gain	1.0000
17:4673675:CTG:C	acceptor_loss	1.0000
17:4673676:T:A	acceptor_loss	1.0000
17:4674505:CCCA:C	donor_gain	1.0000
17:4674507:CA:C	donor_loss	1.0000
17:4674508:AC:A	donor_loss	1.0000
17:4674509:C:CG	donor_loss	1.0000
17:4674509:CCT:C	donor_gain	1.0000
17:4674665:CGCAG:C	acceptor_gain	1.0000
17:4674666:GCAG:G	acceptor_gain	1.0000
17:4674667:CAG:C	acceptor_gain	1.0000
17:4674667:CAGC:C	acceptor_gain	1.0000
17:4674668:AG:A	acceptor_gain	1.0000
17:4674670:C:CC	acceptor_gain	1.0000
17:4674671:T:C	acceptor_loss	1.0000
17:4674678:A:T	acceptor_gain	1.0000
17:4674952:CCGTG:C	acceptor_gain	1.0000
17:4674953:CGTGC:C	acceptor_gain	1.0000
17:4674955:TG:T	acceptor_gain	1.0000
17:4674957:C:CC	acceptor_gain	1.0000
17:4674963:C:CT	acceptor_gain	1.0000
17:4675057:T:TA	donor_gain	1.0000
17:4675065:T:A	donor_gain	1.0000
17:4675270:TCA:T	donor_loss	1.0000
17:4675271:CAC:C	donor_loss	1.0000
17:4675272:A:AC	donor_gain	1.0000
17:4675272:AC:A	donor_loss	1.0000

AlphaMissense

7209 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:4672336:G:C	S885R	0.999
17:4672336:G:T	S885R	0.999
17:4672338:T:G	S885R	0.999
17:4672343:A:C	I883S	0.999
17:4672343:A:G	I883T	0.999
17:4672345:A:C	N882K	0.999
17:4672345:A:T	N882K	0.999
17:4672349:A:C	I881S	0.999
17:4672349:A:G	I881T	0.999
17:4672349:A:T	I881N	0.999
17:4672622:A:C	I790S	0.999
17:4672622:A:T	I790N	0.999
17:4672630:G:C	S787R	0.999
17:4672630:G:T	S787R	0.999
17:4672632:T:G	S787R	0.999
17:4672645:A:C	S782R	0.999
17:4672645:A:T	S782R	0.999
17:4672647:T:G	S782R	0.999
17:4672658:A:C	I778S	0.999
17:4672658:A:G	I778T	0.999
17:4690917:A:G	W131R	0.999
17:4690917:A:T	W131R	0.999
17:4690986:C:G	G108R	0.999
17:4671489:A:G	C1115R	0.998
17:4671496:G:C	F1112L	0.998
17:4671496:G:T	F1112L	0.998
17:4671498:A:G	F1112L	0.998
17:4672333:A:C	S886R	0.998
17:4672333:A:T	S886R	0.998
17:4672335:T:G	S886R	0.998

dbSNP variants (sampled 300 via entrez): RS1000046313 (17:4681749 A>G), RS1000071255 (17:4704230 T>C,G), RS1000181964 (17:4669949 T>C), RS1000212302 (17:4686767 C>A,G), RS1000254067 (17:4670185 A>C,G), RS1000297797 (17:4670304 CA>C,CAA), RS1000308024 (17:4701812 G>T), RS1000450982 (17:4676228 G>A), RS1000655399 (17:4694532 C>T), RS1000655728 (17:4675741 C>T), RS1000904640 (17:4700130 C>T), RS1000951557 (17:4688324 G>A), RS1000978241 (17:4697647 T>C), RS1001130260 (17:4705554 T>C), RS1001253388 (17:4700367 G>A)

Disease associations

OMIM: gene MIM:609455 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005975_1	Eosinophil count	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523653 (PROTEIN-PROTEIN INTERACTION), CHEMBL6067535 (SINGLE PROTEIN)

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.40	IC50	40	nM	CHEMBL3427044
6.54	Kd	289.8	nM	CHEMBL5653589
6.54	ED50	289.8	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 3 total; 2 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
methyl 3-(2-methylpropoxy)-4-[[3-(2-methylpropoxy)-4-nitrobenzoyl]amino]benzoate	1637457: Inhibition of full length AR/PELP1 (unknown origin) interaction expressed in human LNCaP cells preincubated for 2 hrs followed by DHT addition measured after 24 hrs by Western blot analysis	ic50	0.0400	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148976: Binding affinity to human PELP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.2898	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects binding, affects reaction, increases reaction, decreases expression, increases expression	5
bisphenol A	increases reaction, decreases expression, increases methylation, affects binding, affects reaction (+1 more)	4
sodium arsenite	increases expression	2
bisphenol S	decreases reaction, increases reaction, decreases methylation, affects binding	2
bisphenol AF	affects binding, affects reaction, affects folding	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
lead acetate	increases expression	1
arsenite	decreases expression	1
cupric chloride	increases expression	1
coumarin	affects phosphorylation	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Resveratrol	increases expression	1
Temozolomide	increases expression	1
Fulvestrant	decreases expression	1
Cadmium	decreases expression	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
Dihydrotestosterone	affects binding, increases reaction	1
Tamoxifen	affects binding, decreases reaction	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4480100	Binding	Inhibition of full length AR/PELP1 (unknown origin) interaction expressed in human LNCaP cells preincubated for 2 hrs followed by DHT addition measured after 24 hrs by Western blot analysis	Non-canonical modulators of nuclear receptors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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