PHIP pleckstrin homology domain interacting protein [Homo sapiens (human)] - Gene

Summary

Official Symbol: PHIPprovided by HGNC
Official Full Name: pleckstrin homology domain interacting proteinprovided by HGNC
Primary source: HGNC:HGNC:15673
See related: Ensembl:ENSG00000146247 MIM:612870; AllianceGenome:HGNC:15673
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ndrp; BRWD2; DIDOD; RepID; WDR11; DCAF14; CHUJANS
Summary: 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. [provided by RefSeq, Oct 2016]
Expression: Ubiquitous expression in bone marrow (RPKM 13.2), endometrium (RPKM 7.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6q14.1

Exon count:: 41

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (78934419..79078254, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (80112128..80255969, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (79644136..79787971, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A trivalent nucleosome interaction by PHIP/BRWD2 is disrupted in neurodevelopmental disorders and cancer.
Title: A trivalent nucleosome interaction by PHIP/BRWD2 is disrupted in neurodevelopmental disorders and cancer.
DCAF14 promotes stalled fork stability to maintain genome integrity.
Title: DCAF14 promotes stalled fork stability to maintain genome integrity.
Molecular double clips within RepID WD40 domain control chromatin binding and CRL4-substrate assembly.
Title: Molecular double clips within RepID WD40 domain control chromatin binding and CRL4-substrate assembly.
Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription.
Title: Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription.
Discovery of a hidden transient state in all bromodomain families.
Title: Discovery of a hidden transient state in all bromodomain families.
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.
Title: PHIP drives glioblastoma motility and invasion by regulating the focal adhesion complex.
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.
Title: The RepID-CRL4 ubiquitin ligase complex regulates metaphase to anaphase transition via BUB3 degradation.
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.
Title: Role of Elevated PHIP Copy Number as a Prognostic and Progression Marker for Cutaneous Melanoma.
The replication initiation determinant protein PHIP modulates replication by recruiting CUL4 to chromatin.
Title: The replication initiation determinant protein (RepID) modulates replication by recruiting CUL4 to chromatin.
These results provide further support for PHIP as a molecular prognostic marker of melanoma, and reveal a significant linkage between PHIP levels and ulceration.
Title: Prognostic impact of PHIP copy number in melanoma: linkage to ulceration.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome MedGen: C4693860 OMIM: 617991 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2022-04-13) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2022-04-13) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH76061 (e-PCR)
- UniSTS:90138

MARC_15335-15336:1013436983:1 (e-PCR)
- UniSTS:267816

MARC_15335-15336:1031934023:1 (e-PCR)
- UniSTS:267816

SHGC-82298 (e-PCR)
- UniSTS:104239

RH80650 (e-PCR)
- UniSTS:88898

SHGC-112293 (e-PCR)
- UniSTS:168595

RH46720 (e-PCR)
- UniSTS:10139

D6S2044 (e-PCR)
- UniSTS:10140

PHIP__5685 (e-PCR)
- UniSTS:463800

Bdy14g08 (e-PCR)
- UniSTS:69050

RH94050 (e-PCR)
- UniSTS:91580

RH119694 (e-PCR)
- UniSTS:133063

RH78623 (e-PCR)
- UniSTS:28925

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables insulin receptor binding	NAS Non-traceable Author Statement more info	PubMed
enables lysine-acetylated histone binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in cytoskeleton organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in insulin receptor signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within negative regulation of extrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cell population proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of insulin-like growth factor receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of mitotic nuclear division	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cell shape	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: PH-interacting protein

Names: DDB1 and CUL4 associated factor 14; IRS-1 PH domain-binding protein; WD repeat-containing protein 11

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_051932.1 RefSeqGene

Range

5045..148880

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_017934.7 → NP_060404.4 PH-interacting protein

Status: REVIEWED

Source sequence(s)

AL450327, BF934406, BQ006356, DA500781, DQ924532

Consensus CDS

CCDS4987.1

UniProtKB/Swiss-Prot

A7J992, B2RPK4, Q05CQ9, Q5VVH4, Q66I29, Q69YV1, Q8NBZ5, Q8WWQ0, Q96H52, Q96ME2, Q9H261

UniProtKB/TrEMBL

A0A8V8TPK0

Related

ENSP00000275034.3, ENST00000275034.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

78934419..79078254 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005248729.6 → XP_005248786.1 PH-interacting protein isoform X1

UniProtKB/TrEMBL

A0A8V8TPK0, A0A8V8TPV5

Related

ENSP00000514809.1, ENST00000700115.1

Conserved Domains (5) summary

cd05496
Location:1315 → 1433

Bromo_WDR9_II; Bromodomain; WDR9 repeat II_like subfamily. WDR9 is a human gene located in the Down Syndrome critical region-2 of chromosome 21. It encodes for a nuclear protein containing WD40 repeats and two bromodomains, which may function as a transcriptional ...

cd05529
Location:1147 → 1262

Bromo_WDR9_I_like; Bromodomain; WDR9 repeat I_like subfamily. WDR9 is a human gene located in the Down Syndrome critical region-2 of chromosome 21. It encodes for a nuclear protein containing WD40 repeats and two bromodomains, which may function as a transcriptional ...

COG2319
Location:178 → 538

WD40; WD40 repeat [General function prediction only]

cd00200
Location:175 → 495

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:186 → 223

7WD40; WD40 repeat [structural motif]
XM_011535918.4 → XP_011534220.1 PH-interacting protein isoform X2

UniProtKB/TrEMBL

A0A8V8TQM4

Conserved Domains (5) summary

cd05496
Location:1144 → 1262

Bromo_WDR9_II; Bromodomain; WDR9 repeat II_like subfamily. WDR9 is a human gene located in the Down Syndrome critical region-2 of chromosome 21. It encodes for a nuclear protein containing WD40 repeats and two bromodomains, which may function as a transcriptional ...

cd05529
Location:976 → 1091

Bromo_WDR9_I_like; Bromodomain; WDR9 repeat I_like subfamily. WDR9 is a human gene located in the Down Syndrome critical region-2 of chromosome 21. It encodes for a nuclear protein containing WD40 repeats and two bromodomains, which may function as a transcriptional ...

COG2319
Location:6 → 366

WD40; WD40 repeat [General function prediction only]

cd00200
Location:3 → 323

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:14 → 51

7WD40; WD40 repeat [structural motif]
XM_011535919.2 → XP_011534221.1 PH-interacting protein isoform X3

Conserved Domains (3) summary

COG2319
Location:178 → 538

WD40; WD40 repeat [General function prediction only]

cd00200
Location:175 → 495

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

sd00039
Location:186 → 223

7WD40; WD40 repeat [structural motif]

Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

80112128..80255969 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054355760.1 → XP_054211735.1 PH-interacting protein isoform X1

UniProtKB/TrEMBL

A0A8V8TPK0
XM_054355761.1 → XP_054211736.1 PH-interacting protein isoform X2

UniProtKB/TrEMBL

A0A8V8TQM4
XM_054355762.1 → XP_054211737.1 PH-interacting protein isoform X3