PHB1

Summary

PHB1 (prohibitin 1, HGNC:8912) is a protein-coding gene on chromosome 17q21.33, encoding Prohibitin 1 (P35232). Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors in the nucleus. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

This gene is evolutionarily conserved, and its product is proposed to play a role in human cellular senescence and tumor suppression. Antiproliferative activity is reported to be localized to the 3’ UTR, which is proposed to function as a trans-acting regulatory RNA. Several pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5245 — RefSeq curated summary.

At a glance

• GWAS associations: 26
• Clinical variants (ClinVar): 26 total
• Phenotypes (HPO): 3
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_002634

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8912
Approved symbol	PHB1
Name	prohibitin 1
Location	17q21.33
Locus type	gene with protein product
Status	Approved
Aliases	BAP32
Ensembl gene	ENSG00000167085
Ensembl biotype	protein_coding
OMIM	176705
Entrez	5245

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 27 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000300408, ENST00000393345, ENST00000419140, ENST00000434917, ENST00000446735, ENST00000504124, ENST00000506273, ENST00000507748, ENST00000508009, ENST00000511832, ENST00000511933, ENST00000512041, ENST00000513412, ENST00000614445, ENST00000617874, ENST00000696365, ENST00000903592, ENST00000903593, ENST00000903594, ENST00000903595, ENST00000903596, ENST00000903597, ENST00000929390, ENST00000929391, ENST00000929392, ENST00000929393, ENST00000929394, ENST00000929395, ENST00000929396, ENST00000929397, ENST00000929398, ENST00000929399, ENST00000929400, ENST00000929401, ENST00000929402

RefSeq mRNA: 4 — MANE Select: NM_002634 NM_001281496, NM_001281497, NM_001281715, NM_002634

CCDS: CCDS11548, CCDS62244

Canonical transcript exons

ENST00000300408 — 7 exons

Exon	Start	End
ENSE00001109483	49404052	49405204
ENSE00002044676	49414835	49414882
ENSE00003485677	49411678	49411839
ENSE00003607885	49413177	49413291
ENSE00003658538	49409331	49409473
ENSE00003788214	49406759	49406854
ENSE00003967149	49409042	49409158

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 98.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.3924 / max 531.8351, expressed in 1779 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166805	16.2509	1764
166806	3.3643	1547
166804	0.7772	482

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.84	gold quality
rectum	UBERON:0001052	98.30	gold quality
islet of Langerhans	UBERON:0000006	97.76	gold quality
transverse colon	UBERON:0001157	97.71	gold quality
right atrium auricular region	UBERON:0006631	97.70	gold quality
apex of heart	UBERON:0002098	97.68	gold quality
minor salivary gland	UBERON:0001830	97.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.58	gold quality
right adrenal gland	UBERON:0001233	97.55	gold quality
heart left ventricle	UBERON:0002084	97.55	gold quality
cardiac ventricle	UBERON:0002082	97.38	gold quality
left adrenal gland	UBERON:0001234	97.35	gold quality
right adrenal gland cortex	UBERON:0035827	97.31	gold quality
body of stomach	UBERON:0001161	97.23	gold quality
gastrocnemius	UBERON:0001388	97.19	gold quality
left adrenal gland cortex	UBERON:0035825	97.12	gold quality
muscle of leg	UBERON:0001383	97.11	gold quality
heart	UBERON:0000948	97.07	gold quality
saliva-secreting gland	UBERON:0001044	97.07	gold quality
stromal cell of endometrium	CL:0002255	97.05	gold quality
ganglionic eminence	UBERON:0004023	97.04	gold quality
cardiac atrium	UBERON:0002081	97.03	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.02	gold quality
lower esophagus	UBERON:0013473	97.01	gold quality
adult mammalian kidney	UBERON:0000082	96.97	gold quality
metanephros cortex	UBERON:0010533	96.89	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.87	gold quality
mouth mucosa	UBERON:0003729	96.79	gold quality
left coronary artery	UBERON:0001626	96.77	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.75	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	20.32
E-MTAB-10042	yes	13.29
E-CURD-112	yes	10.74
E-MTAB-3929	no	1294.59
E-HCAD-8	no	43.39
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
AR	Repression
FBXO7	Activation

Upstream regulators (CollecTRI, top): AR, ESR1, HDAC1, HDAC2, HSF1, MYC, MYCN, STAT3, TP53, VDR

miRNA regulators (miRDB)

75 targeting PHB1, 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-4455	100.00	65.48	1587
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-609	99.82	64.26	505
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Data show that prohibitin recruits Brg-1/Brm to E2F-responsive promoters, and that this recruitment is required for the repression of E2F-mediated transcription by prohibitin. (PMID:12065415)
• Differential regulation of Rb family proteins and prohibitin during camptothecin-induced apoptosis. (PMID:12085232)
• appears to repress E2F-mediated transcription utilizing different molecular mediators and facilitate channeling of specific signaling pathways to the cell cycle machinery (PMID:12466959)
• The prohibitin 3’ untranslated region polymorphism is not associated with risk of ovarian cancer. (PMID:12821355)
• Prohibitin appears to induce p53-mediated transcription by enhancing its recruitment to promoters (PMID:14500729)
• Here we show that the E2F1 binding domain of prohibitin has the potential to fold into a coiled-coil structure. (PMID:14637159)
• PHB is required for growth suppression by estrogen antagonists. (PMID:15141164)
• Data indicate that the novel 3’ untranslated region of prohibitin influences not only the tumorigenic phenotype but also may play a role in differentiation and migration of breast cancer cells. (PMID:15614618)
• PHB might be a useful therapeutic approach for the treatment of variety of disease states, including inflammation, obesity and cancer. (PMID:15823758)
• Prohibitin plays a role in the activation of the Ras-Raf signalling pathway and in modulating epithelial cell adhesion and migration. (PMID:16041367)
• Findings in this review demonstrate an unexpected role of PHB in the control of a central signaling pathway involved in cell growth and malignant transformation. (PMID:16294014)
• study demonstrated that prohibitin 1 may be activated at the early stage of glandular neoplasia of the uterine cervix (PMID:16426920)
• These studies show that prohibitin plays a vital role in inducing cellular senescence. (PMID:16705168)
• These studies show that prohibitin can have diverse effects on the expression of different genes and the activity of various cellular promoters is affected by prohibitin (PMID:16918502)
• TGF-ss mediated the nuclear export of prohibitin, a protein involved in androgen-regulated prostate growth, to the cytosol in prostate cancer cells. (PMID:16951178)
• appears then that repression of androgen receptor (AR) activity is one mechanism by which prohibitin inhibits androgen-dependent growth of prostate cells (PMID:16964284)
• the PHB 3’UTR T allele increases the risk of breast cancer in patients who are already at increased risk of disease. (PMID:17004108)
• PHB protein was positively expressed at normal renal tissues, strongly down-regulated in renal biopsy specimens, and negatively correlated with the expression of alpha-smooth-muscle actin (alpha-SMA) and with the degrees of tubulointerstitial lesions. (PMID:17043753)
• A significant reduction of prohibitin and ATP synthase was observed in the substantia nigra in PD cases. In contrast, increased prohibitin and ATP synthase levels were found in the frontal cortex in PD. (PMID:17284347)
• The prohibitin 3’ UTR polymorphism was not associated with risk and prognosis of ovarian cancer in Caucasian women. (PMID:17544200)
• With RNF2, regulates the activity of E2F1 transcription factor via dual pathways. (PMID:17873902)
• Results indicate that PHB functions as a transcriptional corepressor for ERalpha in vitro and in vivo, and that its heteromerization with REA acts as a novel mechanism to limit its corepressor activity. (PMID:17932104)
• Phb1 and Phb2 are novel phosphoproteins up-regulated during T cell activation that function to maintain mitochondrial integrity (PMID:18086671)
• Phb1 over-expression induced cellular resistance to Staurosporine via the intrinsic apoptotic pathway. Phb1 induces block at G0/G1 phase of the cell cycle and promotes survival of cancer cells. (PMID:18183577)
• PHB1 maintains the organization and copy number of the mtDNA through both TFAM-independent and -dependent pathways. (PMID:18258228)
• The prohibitin 3’UTR C-to-T transition variant is not associated with the risk of breast cancer in Turkish women. (PMID:18494604)
• PHB could be a potential diagnostic and differentiation biomarker of gastric cancer for tissue-based detection by immunohistochemistry and real-time PCR, but not for serum-based detection. (PMID:18709484)
• PHB is a nuclear matrix protein, which is located in the nuclear matrix, and the distribution and expression of PHB and its relation with associated genes may play significant roles during the differentiation of SMMC-7721 hepatocarcinoma cells (PMID:18763282)
• MicroRNA-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitin (PMID:18789835)
• This protein has been found differentially expressed in the temporal lobe from patients with schizophrenia. (PMID:19034380)
• PHB 1630 C/T single nucleotide polymorphism was associated with breast cancers with clinical features typical for BRCA1-positive tumours (PMID:19071013)
• the presence of the braf protein mutation increases PHB promoter activity and therefore potentially mediates effects of this mutation on the behavior of BRAF protein (PMID:19207009)
• O-GlcNAc modification and tyrosine phosphorylation of PHB play an important role in tyrosine kinase signaling pathways (PMID:19238206)
• Prohibitin is a novel regulator of antioxidant response that attenuates colonic inflammation in mice. (PMID:19327358)
• HCV core protein interacts with prohibitin and represses the interaction between prohibitin and subunit proteins of cytochrome c oxidase. (PMID:19591124)
• Severe acute respiratory syndrome coronavirus nonstructural protein 2 interacts with a host protein complex of PHB1 and PHB2 involved in mitochondrial biogenesis and intracellular signaling (PMID:19640993)
• Upregulation of prohibitin was significantly associated with proliferation, invasion depth and lymph node metastasis of ESCC. statistically significant correlations between expression of beta-catenin and prohibitin. (PMID:19664078)
• PHB inhibits NF-kappaB nuclear translocation via a new mechanism involving importin alpha3 levels. TNFA decreases PHB expression in intestinal epithelial cells. PHB restoration protects against the bad effects of TNF-alpha & NF-kappaB on barrier function. (PMID:19710421)
• Induction of TGF-beta apoptosis is mediated by Smad-dependent and Smad-independent MAP kinase signaling converges at prohibin as a downstream effector regulating inner mitochondrial permeability. (PMID:19725029)
• ginsenoside Rg1, cinnamic acid, and tanshinone IIA cause downregulation of prohibitin and its translocation from nucleus to cytoplasm during the differentiation of osteosarcoma MG-63 cells (PMID:19725052)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	phb	ENSDARG00000057414
mus_musculus	Phb1	ENSMUSG00000038845
rattus_norvegicus	AABR07037878.1	ENSRNOG00000032797
drosophila_melanogaster	Phb1	FBGN0002031
caenorhabditis_elegans	phb-1	WBGENE00004014

Paralogs (1): PHB2 (ENSG00000215021)

Protein

Protein identifiers

Prohibitin 1 — P35232 (reviewed: P35232)

All UniProt accessions (6): A8K401, C9JW96, C9JZ20, E7ESE2, E9PCW0, P35232

UniProt curated annotations — full annotation on UniProt →

Function. Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors in the nucleus. Plays a role in adipose tissue and glucose homeostasis in a sex-specific manner. Contributes to pulmonary vascular remodeling by accelerating proliferation of pulmonary arterial smooth muscle cells. In the mitochondria, together with PHB2, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as a chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan. The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner. Regulates mitochondrial respiration activity playing a role in cellular aging. The prohibitin complex plays a role of mitophagy receptor involved in targeting mitochondria for autophagic degradation. Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6. In the nucleus, acts as a transcription coregulator, enhances promoter binding by TP53, a transcription factor it activates, but reduces the promoter binding by E2F1, a transcription factor it represses. Interacts with STAT3 to affect IL17 secretion in T-helper Th17 cells. In the plasma membrane, cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates. Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation.

Subunit / interactions. The mitochondrial prohibitin complex consists of two subunits (PHB1 and PHB2), assembled into a membrane-associated ring-shaped supercomplex of approximately 1 mDa. Interacts with STOML2. Interacts with MAP1LC3B (membrane-bound form LC3-II); the interaction requires PHB2 and takes place upon Parkin-mediated mitochondrial damage. Interacts with STAT3 (unphosphorylated or phosphorylated at ‘Ser-727’). Interacts with CLPB. Interacts with CD86 (via cytoplasmic domain); the interactions increases after priming with CD40. (Microbial infection) Interacts with SARS coronavirus/SARS-CoV nsp2 protein. (Microbial infection) Interacts with chikungunya virus spike glycoprotein E2. (Microbial infection) Interaction with human immunodeficiency virus type 1/HIV-1 envelope glycoprotein GP160. (Microbial infection) Interacts with human enterovirus 71/EV-71 capsid protein VP0, protein 3CD and protease 3C.

Subcellular location. Mitochondrion inner membrane. Nucleus. Cytoplasm. Cell membrane.

Tissue specificity. Widely expressed in different tissues.

Induction. Expression increases approximately 3-fold upon entry into G1 phase compared with other phases of the cell cycle. Also induced following inhibition of mitochondrial protein synthesis by thiamphenicol.

Similarity. Belongs to the prohibitin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P35232-1	1	yes
P35232-2	2

RefSeq proteins (4): NP_001268425, NP_001268426, NP_001268644, NP_002625* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000163	Prohibitin	Family
IPR001107	Band_7	Domain
IPR036013	Band_7/SPFH_dom_sf	Homologous_superfamily

Pfam: PF01145

UniProt features (13 total): modified residue 7, sequence variant 2, initiator methionine 1, chain 1, splice variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9O9Z	ELECTRON MICROSCOPY	2.4
9UNL	ELECTRON MICROSCOPY	2.8
9OA0	ELECTRON MICROSCOPY	3.1
8RRH	ELECTRON MICROSCOPY	16.3
9O6S	ELECTRON MICROSCOPY	21
9O6T	ELECTRON MICROSCOPY	22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35232-F1	89.36	0.67

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 (7): 2, 91, 128, 186, 202, 202, 249

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-5673000	RAF activation
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-8949664	Processing of SMDT1
R-HSA-9649948	Signaling downstream of RAS mutants

MSigDB gene sets: 407 (showing top): GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, HORIUCHI_WTAP_TARGETS_DN, TSENG_IRS1_TARGETS_UP, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_B_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_REGULATION_OF_INTRACELLULAR_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM

GO Biological Process (36): negative regulation of transcription by RNA polymerase II (GO:0000122), osteoblast differentiation (GO:0001649), positive regulation of immunoglobulin production (GO:0002639), regulation of DNA-templated transcription (GO:0006355), mitochondrion organization (GO:0007005), signal transduction (GO:0007165), negative regulation of cell population proliferation (GO:0008285), positive regulation of gene expression (GO:0010628), obsolete negative regulation of transcription by competitive promoter binding (GO:0010944), negative regulation of cell growth (GO:0030308), positive regulation of interleukin-17 production (GO:0032740), RIG-I signaling pathway (GO:0039529), epigenetic regulation of gene expression (GO:0040029), B cell activation (GO:0042113), negative regulation of protein catabolic process (GO:0042177), regulation of apoptotic process (GO:0042981), positive regulation of neuron apoptotic process (GO:0043525), host-mediated perturbation of viral RNA genome replication (GO:0044830), positive regulation of G protein-coupled receptor signaling pathway (GO:0045745), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of complement activation (GO:0045917), symbiont entry into host cell (GO:0046718), positive regulation of smooth muscle cell proliferation (GO:0048661), protein stabilization (GO:0050821), progesterone receptor signaling pathway (GO:0050847), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), negative regulation of androgen receptor signaling pathway (GO:0060766), negative regulation of ERK1 and ERK2 cascade (GO:0070373), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to interleukin-6 (GO:0071354), DNA biosynthetic process (GO:0071897), T-helper 17 type immune response (GO:0072538), antiviral innate immune response (GO:0140374), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), negative regulation of nuclear receptor-mediated glucocorticoid signaling pathway (GO:2000323)

GO Molecular Function (8): complement component C3a binding (GO:0001850), complement component C3b binding (GO:0001851), transcription corepressor activity (GO:0003714), enzyme binding (GO:0019899), proteinase activated receptor binding (GO:0031871), histone deacetylase binding (GO:0042826), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (11): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), early endosome (GO:0005769), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), mitochondrial prohibitin complex (GO:0035632), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Oncogenic MAPK signaling	2
RAF/MAP kinase cascade	1
Mitochondrial calcium ion transport	1
Signaling by RAS mutants	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of gene expression	3
negative regulation of DNA-templated transcription	2
DNA-templated transcription	2
negative regulation of cellular process	2
complement binding	2
intracellular membrane-bounded organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
ossification	1
cell differentiation	1
immunoglobulin production	1
regulation of immunoglobulin production	1
positive regulation of production of molecular mediator of immune response	1
regulation of RNA biosynthetic process	1
organelle organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
positive regulation of cytokine production	1
interleukin-17 production	1
regulation of interleukin-17 production	1
cytoplasmic pattern recognition receptor signaling pathway	1
chromatin remodeling	1
lymphocyte activation	1
negative regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
negative regulation of protein metabolic process	1
apoptotic process	1
regulation of programmed cell death	1

Protein interactions and networks

STRING

4692 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHB1	ERLIN2	O94905	988
PHB1	PHB2	Q99623	988
PHB1	ERLIN1	O75477	981
PHB1	STOM	P27105	937
PHB1	DNAJC19	Q96DA6	762
PHB1	HSPA9	P30036	760
PHB1	STOML2	Q9UJZ1	750
PHB1	VDAC2	P45880	698
PHB1	YME1L1	Q96TA2	689
PHB1	RAF1	P04049	685
PHB1	ATP23	Q9Y6H3	675
PHB1	VDAC1	P21796	655
PHB1	CYCS	P00001	646
PHB1	IMMT	Q16891	639
PHB1	ACTB	P02570	631

IntAct

294 interactions, top by confidence:

A	B	Type	Score
NDUFS3	NDUFS2	psi-mi:“MI:0914”(association)	0.850
NDUFS2	NDUFS3	psi-mi:“MI:0914”(association)	0.850
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
RAB11A	EVI5	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MAP4K1	HSP90AB1	psi-mi:“MI:0914”(association)	0.670
rep	PHB1	psi-mi:“MI:0914”(association)	0.640
rep	EIF4E2	psi-mi:“MI:0914”(association)	0.640
PHB1	TP53	psi-mi:“MI:0403”(colocalization)	0.620
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
PHB1	STAT3	psi-mi:“MI:0915”(physical association)	0.600
PHB1	STAT3	psi-mi:“MI:0403”(colocalization)	0.600
PHB1	PHB2	psi-mi:“MI:0915”(physical association)	0.590
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
PHB1	SEC22A	psi-mi:“MI:0915”(physical association)	0.560
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
Tnfrsf19	PHB1	psi-mi:“MI:0915”(physical association)	0.520
LONRF3	PHB1	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (1437): PHB (Affinity Capture-MS), PHB (Affinity Capture-MS), PHB (Affinity Capture-MS), PHB (Affinity Capture-MS), PHB (Affinity Capture-MS), PHB (Affinity Capture-MS), PHB (Affinity Capture-MS), PHB (Affinity Capture-MS), PHB (Affinity Capture-MS), ATL3 (Co-fractionation), BCAP29 (Co-fractionation), BCAP31 (Co-fractionation), PHB (Co-fractionation), PHB (Co-fractionation), PHB (Co-fractionation)

ESM2 similar proteins: A3QK16, B5DEH2, B5DGH9, B9N1F9, O54734, O54956, O75477, O89000, O94905, P11029, P11497, P35232, P48440, P67778, P67779, P84173, Q05AY2, Q12882, Q13085, Q1LUA8, Q1RMU4, Q28007, Q28559, Q28943, Q28DX1, Q28J34, Q39258, Q3B8M3, Q3T165, Q58EG2, Q5R7C5, Q5R895, Q5RCJ9, Q5SWU9, Q5XH03, Q5ZLA5, Q641X8, Q641Y0, Q6DKC0, Q6DRI1

Diamond homologs: A9UMS3, H1VAN0, H1VPS8, O04331, O35129, O49460, O94550, P24156, P35232, P40961, P50085, P50093, P67778, P67779, P84173, P86220, Q2HJ97, Q3T165, Q54GI9, Q54Q31, Q5RB19, Q5XIH7, Q5ZMN3, Q99623, Q9BKU4, Q9FFH5, Q9LK25, Q9LY99, Q9P7H3, Q9SIL6, Q9ZNT7

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
KIT	“up-regulates activity”	PHB	phosphorylation
PHB	“down-regulates quantity by repression”	AR	“transcriptional regulation”
TP53	“up-regulates activity”	PHB	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 209 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
Respiratory electron transport	9	6.4×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, NADH to ubiquinone	6	12.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

955 predictions. Top by Δscore:

Variant	Effect	Δscore
17:49405200:TCAGC:T	acceptor_gain	1.0000
17:49405201:CAGC:C	acceptor_gain	1.0000
17:49405201:CAGCC:C	acceptor_gain	1.0000
17:49405202:AGCC:A	acceptor_loss	1.0000
17:49405203:GC:G	acceptor_gain	1.0000
17:49405203:GCC:G	acceptor_loss	1.0000
17:49405204:CC:C	acceptor_gain	1.0000
17:49405204:CCTA:C	acceptor_loss	1.0000
17:49405205:C:CC	acceptor_gain	1.0000
17:49406753:GCTCA:G	donor_loss	1.0000
17:49406754:CTCAC:C	donor_loss	1.0000
17:49406755:TCACC:T	donor_loss	1.0000
17:49406756:CACCT:C	donor_loss	1.0000
17:49406757:A:AT	donor_loss	1.0000
17:49406758:C:G	donor_loss	1.0000
17:49406850:TGTGT:T	acceptor_gain	1.0000
17:49406851:GTGT:G	acceptor_gain	1.0000
17:49406852:TGT:T	acceptor_gain	1.0000
17:49406854:TCTA:T	acceptor_loss	1.0000
17:49406855:C:A	acceptor_loss	1.0000
17:49406855:C:CC	acceptor_gain	1.0000
17:49406856:T:G	acceptor_loss	1.0000
17:49407278:C:A	donor_gain	1.0000
17:49409038:TTACC:T	donor_loss	1.0000
17:49409040:A:AC	donor_gain	1.0000
17:49409040:ACCA:A	donor_loss	1.0000
17:49409041:C:CC	donor_gain	1.0000
17:49409041:C:T	donor_loss	1.0000
17:49409154:CGAGC:C	acceptor_gain	1.0000
17:49409155:GAGC:G	acceptor_gain	1.0000

AlphaMissense

1747 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:49405081:C:G	A244P	1.000
17:49405171:C:G	A214P	1.000
17:49405186:C:G	A209P	1.000
17:49405204:C:G	A203P	1.000
17:49406779:C:G	A196P	1.000
17:49406788:C:G	A193P	1.000
17:49406800:C:G	A189P	1.000
17:49406821:C:G	A182P	1.000
17:49406828:G:C	F179L	1.000
17:49406828:G:T	F179L	1.000
17:49406829:A:C	F179C	1.000
17:49406829:A:G	F179S	1.000
17:49406830:A:G	F179L	1.000
17:49406840:G:C	F175L	1.000
17:49406840:G:T	F175L	1.000
17:49406842:A:G	F175L	1.000
17:49409091:A:G	L154P	1.000
17:49409136:A:G	L139P	1.000
17:49409466:C:A	Q86H	1.000
17:49409466:C:G	Q86H	1.000
17:49405084:C:G	A243P	0.999
17:49405098:A:G	L238P	0.999
17:49405143:A:G	L223P	0.999
17:49405150:C:G	A221P	0.999
17:49405153:C:G	A220P	0.999
17:49405159:A:G	S218P	0.999
17:49405164:C:T	G216D	0.999
17:49405165:C:G	G216R	0.999
17:49405183:C:G	A210P	0.999
17:49405197:T:G	Q205P	0.999

dbSNP variants (sampled 300 via entrez): RS1001162524 (17:49407624 C>T), RS1001167734 (17:49410822 C>G,T), RS1002000607 (17:49407353 C>T), RS1002288697 (17:49413562 G>A), RS1002478332 (17:49411053 G>A,C), RS1002620919 (17:49411952 TTCTC>T), RS1002896145 (17:49415887 T>C), RS1002969906 (17:49415585 C>A), RS1003221642 (17:49409694 G>A,T), RS1003262559 (17:49414543 A>G), RS1003516866 (17:49405684 A>G), RS1003747422 (17:49411441 A>C), RS1003969455 (17:49405670 G>A), RS1004147217 (17:49411895 G>A,C), RS1004341430 (17:49405990 T>A,C)

Disease associations

OMIM: gene MIM:176705 | disease phenotypes: MIM:167000

GenCC curated gene-disease

Mondo (1): ovarian cancer (MONDO:0008170)

Orphanet (1): Rare ovarian cancer (Orphanet:213500)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0003002	Breast carcinoma

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST000394_6	Diastolic blood pressure	5.000000e-09
GCST001942_17	Prostate cancer	2.000000e-09
GCST004377_1	Restricted and repetitive behaviours in autism spectrum disorder	2.000000e-08
GCST004493_9	Lower body strength	9.000000e-06
GCST005194_180	Coronary artery disease	1.000000e-12
GCST005212_35	Asthma	7.000000e-09
GCST005275_26	Cancer	7.000000e-07
GCST006862_3	Asthma	3.000000e-09
GCST007094_54	Diastolic blood pressure	1.000000e-20
GCST007095_125	Systolic blood pressure	1.000000e-07
GCST007098_125	Diastolic blood pressure	4.000000e-13
GCST007098_126	Diastolic blood pressure	1.000000e-09
GCST007099_215	Systolic blood pressure	5.000000e-12
GCST007267_240	Systolic blood pressure	9.000000e-09
GCST007798_104	Asthma	7.000000e-16
GCST007798_105	Asthma	1.000000e-14
GCST007799_9	Asthma (adult onset)	5.000000e-09
GCST007800_3	Asthma (childhood onset)	4.000000e-24
GCST007995_5	Asthma (childhood onset)	1.000000e-11
GCST009391_336	Metabolite levels	8.000000e-07
GCST009391_364	Metabolite levels	3.000000e-06
GCST009391_907	Metabolite levels	1.000000e-06
GCST009798_53	Asthma	2.000000e-18
GCST010002_125	Refractive error	1.000000e-44
GCST010043_37	Asthma	6.000000e-28
GCST010866_153	Coronary artery disease	1.000000e-17

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0007999	lower body strength measurement
EFO:0006335	systolic blood pressure
EFO:1002011	adult onset asthma
EFO:0010433	triacylglycerol 56:6 measurement
EFO:0010435	triacylglycerol 56:8 measurement
EFO:0010442	triacylglycerol 58:8 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295750 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.71	Kd	1936	nM	CHEMBL5653589
5.71	ED50	1936	nM	CHEMBL5653589
5.20	Kd	6339	nM	CHEMBL3752910
5.20	ED50	6339	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 12 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148994: Binding affinity to human PHB incubated for 45 mins by Kinobead based pull down assay	kd	1.9357	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148994: Binding affinity to human PHB incubated for 45 mins by Kinobead based pull down assay	kd	6.3393	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects methylation, decreases expression, affects cotreatment	4
Tretinoin	decreases expression	3
bisphenol A	decreases expression, increases expression	2
sodium arsenite	affects expression, affects methylation	2
Acetaminophen	decreases expression	2
Hydrogen Peroxide	affects expression, decreases expression	2
Rotenone	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Particulate Matter	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
quinomethionate	affects expression	1
geraniol	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butylidenephthalide	decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
flavone	decreases expression	1
bicalutamide	decreases reaction, increases expression, affects binding, increases reaction, affects cotreatment	1
seocalcitol	decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases reaction, increases secretion, decreases activity	1
CLIK 148	increases expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
eurycomanone	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4272316	Binding	Downregulation of PHB1 in human HBL cells at 0.1 to 10 uM after 24 to 48 hrs by Western blot analysis	Targeting prohibitin with small molecules to promote melanogenesis and apoptosis in melanoma cells. — Eur J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	PHASE4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	PHASE4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT00001806	PHASE3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	PHASE3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	PHASE3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	PHASE3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002819	PHASE3	TERMINATED	Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Persistent Ovarian Epithelial Cancer
NCT00002894	PHASE3	COMPLETED	Platinum-based Chemotherapy With or Without Paclitaxel in Treating Patients With Relapsed Ovarian Cancer
NCT00002895	PHASE3	COMPLETED	Early Chemotherapy Based on CA 125 Level Alone Compared With Delayed Chemotherapy in Treating Patients With Recurrent Ovarian Epithelial , Fallopian Tube, or Primary Peritoneal Cancer
NCT00003120	PHASE3	COMPLETED	S9701 Paclitaxel in Treating Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission
NCT00003214	PHASE3	COMPLETED	Chemosensitivity Testing to Assign Treatment for Patients With Stage III or Stage IV Ovarian Cancer
NCT00003322	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Primary Peritoneal or Stage III Epithelial Ovarian Cancer
NCT00003636	PHASE3	COMPLETED	Chemotherapy Plus Surgery in Treating Patients With Stage III or Stage IV Ovarian, Peritoneal, or Fallopian Tube Cancer
NCT00003644	PHASE3	COMPLETED	Carboplatin Plus Paclitaxel With or Without Continued Low-Dose Paclitaxel in Treating Patients With Early-Stage Ovarian Cancer