PHIP

Summary

PHIP (PHIP subunit of CUL4-Ring ligase complex, HGNC:15673) is a protein-coding gene on chromosome 6q14.1, encoding PH-interacting protein (Q8WWQ0). Probable regulator of the insulin and insulin-like growth factor signaling pathways. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a protein that binds to the insulin receptor substrate 1 protein and regulates glucose transporter translocation in skeletal muscle cells. The encoded protein may also regulate growth and survival of pancreatic beta cells. Elevated copy number of this gene may be associated with melanoma severity and the encoded protein may promote melanoma metastasis in human patients.

Source: NCBI Gene 55023 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 35
• Clinical variants (ClinVar): 1,222 total — 55 pathogenic, 67 likely-pathogenic
• Phenotypes (HPO): 150
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_017934

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15673
Approved symbol	PHIP
Name	PHIP subunit of CUL4-Ring ligase complex
Location	6q14.1
Locus type	gene with protein product
Status	Approved
Aliases	ndrp, BRWD2, RepID, DCAF14, FLJ20705
Ensembl gene	ENSG00000146247
Ensembl biotype	protein_coding
OMIM	612870
Entrez	55023

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 10 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000275034, ENST00000479165, ENST00000700012, ENST00000700013, ENST00000700114, ENST00000700115, ENST00000700116, ENST00000700117, ENST00000700118, ENST00000700119, ENST00000700120, ENST00000700121, ENST00000700170, ENST00000700171, ENST00000700172, ENST00000913657, ENST00000913658, ENST00000913659, ENST00000913660, ENST00000965196

RefSeq mRNA: 1 — MANE Select: NM_017934 NM_017934

CCDS: CCDS4987

Canonical transcript exons

ENST00000275034 — 40 exons

Exon	Start	End
ENSE00001882565	79078029	79078254
ENSE00002203953	79077448	79077507
ENSE00002215317	79025519	79025619
ENSE00002216601	78958475	78958600
ENSE00002221205	79016544	79016642
ENSE00002223894	78982886	78983117
ENSE00002233843	79077700	79077729
ENSE00002240206	79015630	79015783
ENSE00002242989	79003730	79003858
ENSE00002256478	79015082	79015216
ENSE00002260724	79001899	79002124
ENSE00002268656	79025943	79026164
ENSE00002271531	78988209	78988349
ENSE00002274764	79060478	79060576
ENSE00002276648	78997414	78997597
ENSE00002279905	79017483	79017583
ENSE00002283615	78998254	78998391
ENSE00002284215	78985352	78985428
ENSE00002291883	79042843	79043003
ENSE00002305329	79060668	79060818
ENSE00002306152	79017346	79017386
ENSE00002313596	79019089	79019159
ENSE00002316734	79077855	79077913
ENSE00002320684	78990868	78990985
ENSE00002488451	78955613	78955682
ENSE00003502072	78946001	78946260
ENSE00003505661	78970781	78970888
ENSE00003538688	78970049	78970173
ENSE00003546051	78945300	78945497
ENSE00003548037	78978592	78978711
ENSE00003548073	78961690	78961810
ENSE00003556326	78955232	78955282
ENSE00003576651	78934419	78941330
ENSE00003578644	78963097	78963252
ENSE00003609479	78947623	78947775
ENSE00003610892	78965703	78965764
ENSE00003617603	78946711	78946874
ENSE00003626918	78969835	78969917
ENSE00003631474	78965945	78966056
ENSE00003656104	78954814	78954963

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 97.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.0593 / max 664.6102, expressed in 1819 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74500	26.5714	1807
74501	7.4899	1684
74498	1.8877	755
74499	1.1104	487

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	97.67	gold quality
epithelium of bronchus	UBERON:0002031	97.37	gold quality
ventricular zone	UBERON:0003053	97.35	gold quality
bronchus	UBERON:0002185	97.27	gold quality
endothelial cell	CL:0000115	96.90	gold quality
cerebellar vermis	UBERON:0004720	96.74	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.15	gold quality
pigmented layer of retina	UBERON:0001782	95.90	gold quality
retina	UBERON:0000966	95.87	gold quality
mammary duct	UBERON:0001765	95.80	gold quality
trabecular bone tissue	UBERON:0002483	95.80	gold quality
choroid plexus epithelium	UBERON:0003911	95.73	gold quality
epithelium of nasopharynx	UBERON:0001951	95.62	gold quality
pericardium	UBERON:0002407	95.61	gold quality
nasopharynx	UBERON:0001728	95.60	gold quality
epithelium of mammary gland	UBERON:0003244	95.58	gold quality
cranial nerve II	UBERON:0000941	95.48	gold quality
hair follicle	UBERON:0002073	95.05	gold quality
superficial temporal artery	UBERON:0001614	94.93	gold quality
urethra	UBERON:0000057	94.88	gold quality
seminal vesicle	UBERON:0000998	94.75	gold quality
oviduct epithelium	UBERON:0004804	94.71	gold quality
calcaneal tendon	UBERON:0003701	94.63	gold quality
embryo	UBERON:0000922	94.15	gold quality
upper leg skin	UBERON:0004262	94.08	gold quality
lower lobe of lung	UBERON:0008949	93.94	gold quality
cardia of stomach	UBERON:0001162	93.85	gold quality
CA1 field of hippocampus	UBERON:0003881	93.85	gold quality
cauda epididymis	UBERON:0004360	93.83	gold quality
caput epididymis	UBERON:0004358	93.81	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	42.57
E-ANND-3	yes	10.46
E-GEOD-75140	no	1396.37
E-MTAB-6524	no	274.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

481 targeting PHIP, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-6833-3P	100.00	70.63	3197

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 11)

• The PHIP gene resides on 6q14.1, and although 6q loss has been observed in melanoma, the PHIP locus was preserved in melanoma cell lines and patient samples, and its overexpression was an independent adverse predictor of survival in melanoma patients. (PMID:22511720)
• These results provide further support for PHIP as a molecular prognostic marker of melanoma, and reveal a significant linkage between PHIP levels and ulceration. (PMID:24005052)
• as elevated PHIP copy number appears to be selected for during the progression of primary to metastatic melanoma, these results confirm PHIP as a promising therapeutic target for melanoma. (PMID:29776954)
• The replication initiation determinant protein PHIP modulates replication by recruiting CUL4 to chromatin. (PMID:30018425)
• During mitosis, CRL4 dissociates from RepID and replaces it with RB Binding Protein 7 (RBBP7), which ubiquitinates the SAC mediator BUB3 to enable mitotic exit. (PMID:31911655)
• PHIP drives glioblastoma motility, invasion, and angiogenesis. PHIP regulates expression of focal adhesion proteins and physically interacts with vinculin, mechanisms by which it promotes tumor cell motility and invasion. The presence of elevated PHIP copy number in distinct molecular glioblastoma subtypes provides additional support for its importance to glioblastoma biology. (PMID:32273388)
• Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription. (PMID:32492392)
• Discovery of a hidden transient state in all bromodomain families. (PMID:33468647)
• DCAF14 promotes stalled fork stability to maintain genome integrity. (PMID:33503431)
• Molecular double clips within RepID WD40 domain control chromatin binding and CRL4-substrate assembly. (PMID:34171797)
• A trivalent nucleosome interaction by PHIP/BRWD2 is disrupted in neurodevelopmental disorders and cancer. (PMID:34819353)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	phip	ENSDARG00000015970
mus_musculus	Phip	ENSMUSG00000032253
rattus_norvegicus	Phip	ENSRNOG00000008652
drosophila_melanogaster	BRWD3	FBGN0011785

Paralogs (2): BRWD3 (ENSG00000165288), BRWD1 (ENSG00000185658)

Protein

Protein identifiers

PH-interacting protein — Q8WWQ0 (reviewed: Q8WWQ0)

Alternative names: DDB1- and CUL4-associated factor 14, IRS-1 PH domain-binding protein, WD repeat-containing protein 11

All UniProt accessions (8): Q8WWQ0, A0A8V8TP75, A0A8V8TPB8, A0A8V8TPK0, A0A8V8TPV5, A0A8V8TQM4, A0A8V8TQP5, A0A8V8TQZ3

UniProt curated annotations — full annotation on UniProt →

Function. Probable regulator of the insulin and insulin-like growth factor signaling pathways. Stimulates cell proliferation through regulation of cyclin transcription and has an anti-apoptotic activity through AKT1 phosphorylation and activation. Plays a role in the regulation of cell morphology and cytoskeletal organization.

Subunit / interactions. Interacts with IRS1 and IRS2. Interacts (via bromo domain) with acetylated lysine residues on histone H1.4, histone H3 and H4 (in vitro).

Subcellular location. Nucleus.

Tissue specificity. Expressed in myeloma and epidermoid carcinoma cell lines.

Disease relevance. Chung-Jansen syndrome (CHUJANS) [MIM:617991] An autosomal dominant disorder characterized by developmental delay, intellectual disability, autistic features, anxiety, hypotonia, obesity, and dysmorphic features. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_060404* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001487	Bromodomain	Domain
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR018359	Bromodomain_CS	Conserved_site
IPR019775	WD40_repeat_CS	Conserved_site
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR052060	Bromo_WD_repeat	Family
IPR057451	BRWD/PHIP_AD	Domain
IPR057452	BRWD/PHIP_N	Domain

Pfam: PF00400, PF00439, PF25313, PF25437

UniProt features (92 total): modified residue 25, sequence variant 19, compositionally biased region 11, repeat 8, region of interest 8, helix 6, cross-link 5, sequence conflict 3, turn 3, domain 2, chain 1, strand 1

Structure

Experimental structures (PDB)

146 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5S9G	X-RAY DIFFRACTION	1.09
5S90	X-RAY DIFFRACTION	1.1
5S98	X-RAY DIFFRACTION	1.1
5S9C	X-RAY DIFFRACTION	1.14
5S8X	X-RAY DIFFRACTION	1.15
5S97	X-RAY DIFFRACTION	1.15
5S9J	X-RAY DIFFRACTION	1.15
7FUS	X-RAY DIFFRACTION	1.15
7FUY	X-RAY DIFFRACTION	1.15
7FV2	X-RAY DIFFRACTION	1.15
7FV3	X-RAY DIFFRACTION	1.15
7FV4	X-RAY DIFFRACTION	1.15
7FV5	X-RAY DIFFRACTION	1.15
7FV8	X-RAY DIFFRACTION	1.15
7FVF	X-RAY DIFFRACTION	1.15
7FVG	X-RAY DIFFRACTION	1.15
7FVH	X-RAY DIFFRACTION	1.15
7FVK	X-RAY DIFFRACTION	1.15
7FVL	X-RAY DIFFRACTION	1.15
7FVN	X-RAY DIFFRACTION	1.15
7FVP	X-RAY DIFFRACTION	1.15
7FVQ	X-RAY DIFFRACTION	1.15
5RJJ	X-RAY DIFFRACTION	1.15
5S9B	X-RAY DIFFRACTION	1.15
7FUU	X-RAY DIFFRACTION	1.16
5RJT	X-RAY DIFFRACTION	1.17
5S96	X-RAY DIFFRACTION	1.17
7FV9	X-RAY DIFFRACTION	1.17
5S8F	X-RAY DIFFRACTION	1.18
5S8V	X-RAY DIFFRACTION	1.18

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWQ0-F1	66.57	0.32

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 (30): 136, 641, 659, 674, 677, 683, 692, 879, 880, 881, 911, 1281, 1283, 1296, 1315, 1359, 1405, 1479, 1497, 1525 …

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9013418	RHOBTB2 GTPase cycle

MSigDB gene sets: 866 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_REGULATION_OF_NUCLEAR_DIVISION, MODULE_255, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_VACUOLAR_MEMBRANE, MORF_SNRP70, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP

GO Biological Process (15): regulation of protein phosphorylation (GO:0001932), regulation of transcription by RNA polymerase II (GO:0006357), cytoskeleton organization (GO:0007010), positive regulation of cell population proliferation (GO:0008284), insulin receptor signaling pathway (GO:0008286), regulation of cell shape (GO:0008360), regulation of cell morphogenesis (GO:0022604), negative regulation of apoptotic process (GO:0043066), positive regulation of insulin-like growth factor receptor signaling pathway (GO:0043568), positive regulation of mitotic nuclear division (GO:0045840), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of extrinsic apoptotic signaling pathway (GO:2001237), chromatin organization (GO:0006325), regulation of signal transduction (GO:0009966)

GO Molecular Function (3): insulin receptor binding (GO:0005158), histone reader activity (GO:0140566), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHOBTB GTPase Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
protein phosphorylation	1
regulation of protein modification process	1
regulation of phosphorylation	1
organelle organization	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
regulation of cell morphogenesis	1
regulation of biological quality	1
cell morphogenesis	1
regulation of anatomical structure morphogenesis	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
positive regulation of signal transduction	1
regulation of insulin-like growth factor receptor signaling pathway	1
insulin-like growth factor receptor signaling pathway	1
regulation of mitotic nuclear division	1
positive regulation of nuclear division	1
positive regulation of cell cycle process	1
mitotic nuclear division	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
extrinsic apoptotic signaling pathway	1
negative regulation of apoptotic signaling pathway	1
regulation of extrinsic apoptotic signaling pathway	1
cellular component organization	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
signaling receptor binding	1
nucleosome	1
histone binding	1

Protein interactions and networks

STRING

2612 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHIP	IRAK1BP1	Q5VVH5	575
PHIP	SPATA25	Q9BR10	504
PHIP	IRS2	Q9Y4H2	497
PHIP	LRWD1	Q9UFC0	422
PHIP	CUL4B	Q13620	392
PHIP	ACSS3	Q9H6R3	383
PHIP	ZMYM4	Q5VZL5	378
PHIP	DDB1	Q16531	373
PHIP	GLT8D1	Q68CQ7	367
PHIP	MTCL2	O94964	360
PHIP	SCYL2	Q6P3W7	360
PHIP	ACOT8	O14734	354
PHIP	CRLS1	Q9UJA2	341
PHIP	PLEKHF2	Q9H8W4	335
PHIP	SMARCA4	P51532	334

IntAct

51 interactions, top by confidence:

A	B	Type	Score
CUL4A	COPS2	psi-mi:“MI:0914”(association)	0.640
VHL	PHIP	psi-mi:“MI:0915”(physical association)	0.560
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
PHIP	HNRNPCL2	psi-mi:“MI:0915”(physical association)	0.400
PHIP	TPR	psi-mi:“MI:0915”(physical association)	0.400
PHIP	LMNA	psi-mi:“MI:0915”(physical association)	0.400
PHIP	HSPA5	psi-mi:“MI:0915”(physical association)	0.400
Cbx1		psi-mi:“MI:0914”(association)	0.350
Chaf1a	CBX5	psi-mi:“MI:0914”(association)	0.350
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
Atrx	ELOC	psi-mi:“MI:0914”(association)	0.350
Brwd3	WDR91	psi-mi:“MI:0914”(association)	0.350
CUL4B	GPS1	psi-mi:“MI:0914”(association)	0.350
Cul4a	GPS1	psi-mi:“MI:0914”(association)	0.350
MPHOSPH8	HCFC1	psi-mi:“MI:0914”(association)	0.350
TMPO		psi-mi:“MI:0914”(association)	0.350
EGR1	MAGEB2	psi-mi:“MI:0914”(association)	0.350
Eif3e	RPSA	psi-mi:“MI:0914”(association)	0.350
ORC1	ZNF768	psi-mi:“MI:0914”(association)	0.350
CUL4A	HAX1	psi-mi:“MI:0914”(association)	0.350
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350
CUL4B	APBB1	psi-mi:“MI:0914”(association)	0.350
DCUN1D1	KLHL18	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
TXNIP	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
HMGA1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
HMGN5	SMCHD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (394): CUL4B (Affinity Capture-Western), CUL4A (Affinity Capture-Western), DDB1 (Affinity Capture-Western), PHIP (Affinity Capture-MS), PHIP (Affinity Capture-MS), PHIP (Affinity Capture-MS), DDB1 (Co-fractionation), PHIP (Affinity Capture-MS), PHIP (Proximity Label-MS), PHIP (Proximity Label-MS), PHIP (Proximity Label-MS), PHIP (Affinity Capture-MS), PHIP (Affinity Capture-MS), PHIP (Affinity Capture-MS), PHIP (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IES7, A0JN62, A0JNW5, A2AAE1, A2AGL3, A2RSJ4, A2RT67, A2RUS2, A2RV80, B0LPN4, B1H2P5, E7F240, E9Q401, O00507, O94967, P30957, P48553, P51593, Q14161, Q2LD37, Q3TLI0, Q3UHE1, Q3UVG3, Q3UX43, Q5F361, Q5M7Q1, Q5RAQ5, Q5ZJK1, Q658Y4, Q68CL5, Q6BDS2, Q6P6Y1, Q6TEP1, Q6VNB8, Q7TMY8, Q7TSG1, Q7Z6Z7, Q8BHY8, Q8CB44, Q8CGF6

Diamond homologs: A0A0R4IXF6, A0A7U2QYM2, A2AHJ4, A2AUY4, A2BIL7, B2RRD7, B7ZS37, D4A7T3, E9Q2Z1, F1QW93, F1R5H6, F7DRV9, G5E8P1, O15164, O60885, O74350, O88379, O88665, O95696, P13709, P21675, P25440, P35817, P51123, P53236, P54816, P55201, P87152, Q02206, Q03330, Q07442, Q08D75, Q09948, Q12830, Q15059, Q1LUC3, Q23590, Q32S26, Q338B9, Q4R8Y1

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PHIP	“up-regulates activity”	Cullin4-RBX1-DDB1	binding
PHIP	“up-regulates activity”	IRS1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 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
Regulation of expression of SLITs and ROBOs	6	8.3×	8e-03
Neddylation	7	6.6×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	5	14.7×	4e-03
chromatin organization	6	9.4×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1222 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	55
Likely pathogenic	67
Uncertain significance	498
Likely benign	336
Benign	192

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1073105	NM_017934.7(PHIP):c.1050dup (p.Gly351fs)	Pathogenic
1098849	NM_018117.12(WDR11):c.1255C>T (p.Gln419Ter)	Pathogenic
1098850	NM_018117.12(WDR11):c.2931+1G>A	Pathogenic
1098851	NM_018117.12(WDR11):c.1439del (p.Asn480fs)	Pathogenic
1424195	NC_000006.11:g.(?79650410)(79787785_?)del	Pathogenic
1676029	NM_017934.7(PHIP):c.2668C>T (p.Gln890Ter)	Pathogenic
1686056	NM_017934.7(PHIP):c.2703dup (p.Val902fs)	Pathogenic
1698953	NM_017934.7(PHIP):c.704_705del (p.Asn234_Tyr235insTer)	Pathogenic
1708636	NM_017934.7(PHIP):c.748C>T (p.Arg250Ter)	Pathogenic
1710707	NM_017934.7(PHIP):c.241C>T (p.Arg81Ter)	Pathogenic
1711633	NM_017934.7(PHIP):c.1628_1653+13del	Pathogenic
1722952	NM_017934.7(PHIP):c.2656G>T (p.Glu886Ter)	Pathogenic
2067762	NM_018117.12(WDR11):c.1280T>G (p.Leu427Ter)	Pathogenic
2103265	NM_018117.12(WDR11):c.1153del (p.Leu385fs)	Pathogenic
2227896	NM_017934.7(PHIP):c.2363del (p.Lys788fs)	Pathogenic
2499020	NM_017934.7(PHIP):c.2537+2T>A	Pathogenic
2571255	NM_017934.7(PHIP):c.703del (p.Tyr235fs)	Pathogenic
2630755	NM_017934.7(PHIP):c.2670_2671del (p.Lys891fs)	Pathogenic
2664240	NM_017934.7(PHIP):c.1654-2A>C	Pathogenic
2664242	NM_017934.7(PHIP):c.2306_2309del (p.Pro769fs)	Pathogenic
2664253	NM_017934.7(PHIP):c.820C>T (p.Gln274Ter)	Pathogenic
2762988	NM_017934.7(PHIP):c.815C>G (p.Ser272Ter)	Pathogenic
2785929	NM_017934.7(PHIP):c.1446_1447del (p.Ser484fs)	Pathogenic
3027385	NM_017934.7(PHIP):c.1949_1950delinsGTTG (p.Leu650fs)	Pathogenic
3239498	NM_017934.7(PHIP):c.857dup (p.Ser287fs)	Pathogenic
3359039	NM_017934.7(PHIP):c.1879+1G>A	Pathogenic
3372383	NM_017934.7(PHIP):c.97C>T (p.Gln33Ter)	Pathogenic
3638700	NM_017934.7(PHIP):c.368dup (p.Ala124fs)	Pathogenic
3653303	NM_017934.7(PHIP):c.1300C>T (p.Arg434Ter)	Pathogenic
3764548	NM_017934.7(PHIP):c.2246dup (p.Thr750fs)	Pathogenic

SpliceAI

6172 predictions. Top by Δscore:

Variant	Effect	Δscore
6:78945295:CTTAC:C	donor_loss	1.0000
6:78945297:TAC:T	donor_loss	1.0000
6:78945298:A:C	donor_loss	1.0000
6:78945299:C:G	donor_loss	1.0000
6:78945299:CCTTG:C	donor_gain	1.0000
6:78945495:GTA:G	acceptor_gain	1.0000
6:78945498:C:CC	acceptor_gain	1.0000
6:78945505:A:C	acceptor_gain	1.0000
6:78945994:GTCTT:G	donor_loss	1.0000
6:78945998:TACT:T	donor_loss	1.0000
6:78945999:A:AC	donor_gain	1.0000
6:78946000:C:A	donor_loss	1.0000
6:78946000:C:CC	donor_gain	1.0000
6:78946000:CTT:C	donor_gain	1.0000
6:78946008:C:A	donor_gain	1.0000
6:78946256:CAGGG:C	acceptor_gain	1.0000
6:78946257:AGGG:A	acceptor_gain	1.0000
6:78946258:GGG:G	acceptor_gain	1.0000
6:78946258:GGGC:G	acceptor_loss	1.0000
6:78946259:GG:G	acceptor_gain	1.0000
6:78946259:GGC:G	acceptor_loss	1.0000
6:78946260:GC:G	acceptor_loss	1.0000
6:78946261:C:CC	acceptor_gain	1.0000
6:78946723:C:CT	donor_gain	1.0000
6:78946724:T:TT	donor_gain	1.0000
6:78946870:TAAAT:T	acceptor_gain	1.0000
6:78946872:AAT:A	acceptor_gain	1.0000
6:78946875:C:CC	acceptor_gain	1.0000
6:78946875:CT:C	acceptor_loss	1.0000
6:78947619:ATAC:A	donor_gain	1.0000

AlphaMissense

11990 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:78946852:A:G	L1410P	1.000
6:78947646:A:C	Y1395D	1.000
6:78947656:A:C	N1391K	1.000
6:78947656:A:T	N1391K	1.000
6:78947669:A:G	L1387P	1.000
6:78947732:A:T	V1366D	1.000
6:78947772:A:G	Y1353H	1.000
6:78954845:A:G	F1341S	1.000
6:78954906:A:G	W1321R	1.000
6:78954906:A:T	W1321R	1.000
6:78958543:A:C	F1238L	1.000
6:78958543:A:T	F1238L	1.000
6:78958545:A:G	F1238L	1.000
6:78958581:A:G	W1226R	1.000
6:78958581:A:T	W1226R	1.000
6:78965730:A:G	W1118R	1.000
6:78965730:A:T	W1118R	1.000
6:78965734:A:C	S1116R	1.000
6:78965734:A:T	S1116R	1.000
6:78965736:T:G	S1116R	1.000
6:78965761:C:A	W1107C	1.000
6:78965761:C:G	W1107C	1.000
6:78965762:C:G	W1107S	1.000
6:78965763:A:G	W1107R	1.000
6:78965763:A:T	W1107R	1.000
6:78965948:A:T	V1105D	1.000
6:78966014:C:A	G1083V	1.000
6:78966014:C:T	G1083E	1.000
6:78966015:C:G	G1083R	1.000
6:78966015:C:T	G1083R	1.000

dbSNP variants (sampled 300 via entrez): RS1000011484 (6:78989571 A>G), RS1000038125 (6:79051215 T>C), RS1000043880 (6:79078248 A>G), RS1000044372 (6:78940322 C>T), RS1000047406 (6:78969755 C>A,G), RS1000094732 (6:79076246 G>A), RS1000104981 (6:78995134 C>T), RS1000114851 (6:79002655 T>C,G), RS1000117673 (6:78942094 T>C), RS1000129041 (6:78993298 C>T), RS1000153775 (6:79046451 C>G,T), RS1000163261 (6:79030544 G>C), RS1000177442 (6:78963688 A>G), RS1000185367 (6:79002304 T>G), RS1000227296 (6:78996678 A>G)

Disease associations

OMIM: gene MIM:612870 | disease phenotypes: MIM:617991, MIM:620237, MIM:614858, MIM:146110, MIM:300958, MIM:147950, MIM:616839

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental delay, intellectual disability, obesity, and dysmorphic features	Definitive	Autosomal dominant
PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome	Definitive	Autosomal dominant
hypogonadotropic hypogonadism 14 with or without anosmia	Strong	Autosomal dominant
intellectual developmental disorder, autosomal recessive 78	Strong	Autosomal recessive
hypogonadotropic hypogonadism	Supportive	Autosomal dominant
Kallmann syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome	Definitive	AD

Mondo (15): PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome (MONDO:0035133), microcephaly (MONDO:0001149), intellectual developmental disorder, autosomal recessive 78 (MONDO:0859373), hypogonadotropic hypogonadism 14 with or without anosmia (MONDO:0013926), hypogonadotropic hypogonadism 7 with or without anosmia (MONDO:0007794), amenorrhea (MONDO:0001836), intellectual disability, X-linked 102 (MONDO:0010497), autism spectrum disorder (MONDO:0005258), hypogonadotropic hypogonadism (MONDO:0018555), intellectual disability (MONDO:0001071), exercise intolerance, riboflavin-responsive (MONDO:0014795), CHARGE syndrome (MONDO:0008965), hereditary breast ovarian cancer syndrome (MONDO:0003582), (MONDO:0060712), Kallmann syndrome (MONDO:0018800)

Orphanet (8): PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome (Orphanet:589905), Kallmann syndrome (Orphanet:478), Normosmic congenital hypogonadotropic hypogonadism (Orphanet:432), X-linked intellectual disability-hypotonia-movement disorder syndrome (Orphanet:457260), CHARGE syndrome (Orphanet:138), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

150 total (30 of 150 shown, HPO-id order):

HPO	Term
HP:0000002	Abnormality of body height
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000013	Hypoplasia of the uterus
HP:0000026	Male hypogonadism
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000054	Micropenis
HP:0000104	Renal agenesis
HP:0000118	Phenotypic abnormality
HP:0000134	Female hypogonadism
HP:0000144	Decreased fertility
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000233	Thin vermilion border
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000308	Microretrognathia
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST001525_23	Visceral fat	6.000000e-06
GCST001762_862	Obesity-related traits	5.000000e-06
GCST002233_1	Adiponectin levels	3.000000e-14
GCST002976_5	HIV-1 viral setpoint	6.000000e-06
GCST004093_13	Prostate-specific antigen levels	3.000000e-11
GCST004093_14	Prostate-specific antigen levels	4.000000e-18
GCST004093_15	Prostate-specific antigen levels	1.000000e-35
GCST004093_16	Prostate-specific antigen levels	4.000000e-43
GCST004094_1	Prostate-specific antigen levels (conditioned on lead SNPs)	9.000000e-25
GCST004094_7	Prostate-specific antigen levels (conditioned on lead SNPs)	5.000000e-18
GCST004879_3	Sjögren’s syndrome	6.000000e-06
GCST005316_564	Intelligence (MTAG)	6.000000e-10
GCST005316_565	Intelligence (MTAG)	6.000000e-10
GCST006227_5	Diastolic blood pressure	3.000000e-09
GCST006231_30	Mean arterial pressure	2.000000e-06
GCST007094_26	Diastolic blood pressure	2.000000e-13
GCST007099_78	Systolic blood pressure	4.000000e-09
GCST007267_218	Systolic blood pressure	8.000000e-12
GCST007507_14	Benign prostatic hyperplasia and lower urinary tract symptoms	3.000000e-15
GCST007513_2	Prostate-specific antigen levels	7.000000e-08
GCST007847_101	Type 2 diabetes	3.000000e-09
GCST007847_54	Type 2 diabetes	5.000000e-08
GCST008860_8	Prostate cancer	8.000000e-06
GCST009380_3	Type 2 diabetes (adjusted for BMI)	4.000000e-09
GCST009391_1160	Metabolite levels	1.000000e-06
GCST009391_282	Metabolite levels	2.000000e-06
GCST009391_291	Metabolite levels	2.000000e-06
GCST009391_367	Metabolite levels	4.000000e-06
GCST009614_2	LDL cholesterol levels x loop diuretics use interaction	4.000000e-08
GCST010118_118	Type 2 diabetes	5.000000e-17

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0003939	energy intake
EFO:0004502	adiponectin measurement
EFO:0006319	HIV viral set point measurement
EFO:0004337	intelligence
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0006335	systolic blood pressure
EFO:0008008	lower urinary tract symptom
EFO:0010460	anthranilic acid measurement
EFO:0010424	triacylglycerol 54:6 measurement
EFO:0010425	triacylglycerol 54:7 measurement
EFO:0010435	triacylglycerol 56:8 measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0011013	vaginal microbiome measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D000568	Amenorrhea	C23.550.568.500
D058747	CHARGE Syndrome	C09.218.458.341.186.500.250; C10.597.751.418.341.186.500.250; C10.597.751.941.162.625.250; C11.270.147.500; C11.966.075.375.250; C16.131.077.299.250; C16.320.165; C23.888.592.763.393.341.186.500.500; C23.888.592.763.941.162.625.500
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D017436	Kallmann Syndrome	C12.050.351.875.253.096.750; C12.200.706.316.096.750; C12.800.316.096.750; C16.131.939.316.096.750; C16.320.467; C19.391.119.096.750; C19.391.482.600
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C562785	Idiopathic Hypogonadotropic Hypogonadism (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2176773 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Non-enzymatic BRD containing proteins

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases abundance, increases expression	4
Valproic Acid	affects cotreatment, decreases expression	4
trichostatin A	affects expression, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	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
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	affects expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic	decreases expression, increases abundance	1

ChEMBL screening assays

17 unique, capped per target: 17 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2186998	Binding	Inhibition of His6FLAG-tagged PHIP-BD2 expressed in Escherichia coli assessed as change in melting temperature at 100 uM by thermal shift assay	Fragment-based discovery of bromodomain inhibitors part 2: optimization of phenylisoxazole sulfonamides. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2AL	Abcam HeLa PHIP KO	Cancer cell line	Female
CVCL_TD25	HAP1 PHIP (-) 1	Cancer cell line	Male
CVCL_TD26	HAP1 PHIP (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00328926	PHASE4	TERMINATED	Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L])
NCT01403532	PHASE4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT01454011	PHASE4	COMPLETED	The Effect of Testosterone Replacement on the High Density Lipoprotein Cholesterol Subgroups
NCT01601327	PHASE4	COMPLETED	Effects of Medications in Patients With Hypogonadism
NCT02310074	PHASE4	UNKNOWN	Efficacy and Safety of Pulsatile Gonadotropin Releasing Hormone Pump Treatment in Patients With Idiopathic Hypogonadotropic Hypogonadism
NCT02880280	PHASE4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03490513	PHASE4	COMPLETED	Aromatase Inhibitors and Weight Loss in Severely Obese Men With Hypogonadism
NCT04456296	PHASE4	COMPLETED	A Study of the Effect of Testosterone Replacement Therapy on Blood Pressure in Adult Male Participants With Hypogonadism
NCT05205837	PHASE4	TERMINATED	A Randomized, Double-blinded, Clinical, Placebo-controlled Trial on the Effects of Therapy With Letrozole and hUman Choriongonadotropin in Male Hypogonadism Induced by Illicit Use of Anabolic Androgenic Steroids- The LUCAS Trial
NCT03687606	PHASE4	UNKNOWN	Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
NCT01103518	PHASE4	UNKNOWN	Ethinyl Estradiol and Cyproterone Acetate in Irregular Menstruation
NCT01206153	PHASE4	COMPLETED	Metformin for Treatment Antipsychotic Induced Amenorrhea in Female Schizophrenic Patients
NCT02393482	PHASE4	UNKNOWN	Psychological Impact of Amenorrhea in Women With Endometriosis
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00467870	PHASE3	COMPLETED	Long-term Safety Study of Intramuscular Injections of 750 mg and 1000 mg Testosterone Undecanoate in Hypogonadal Men
NCT00962637	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal™ Treatment in Men With Secondary Hypogonadism
NCT01067365	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal Treatment in Men With Secondary Hypogonadism
NCT01532414	PHASE3	COMPLETED	Phase III Study to Evaluated Morning Testosterone Normalization in Men With Secondary Hypogonadism
NCT01534208	PHASE3	COMPLETED	Safety Study of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism
NCT01709331	PHASE3	COMPLETED	A Study of the Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adult Men With Hypogonadotropic Hypogonadism (HH) (P07937)