PHIP

pleckstrin homology domain interacting protein, the group of DDB1 and CUL4 associated factors|WD repeat domain containing|Bromodomain containing

Basic information

Region (hg38): 6:78934419-79078287

Previous symbols: [ "WDR11" ]

Links

ENSG00000146247 ∙ NCBI:55023 ∙ OMIM:612870 ∙ HGNC:15673 ∙ Uniprot:Q8WWQ0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental delay, intellectual disability, obesity, and dysmorphic features (Definitive), mode of inheritance: AD
• PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome (Supportive), mode of inheritance: AD
• PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome (Strong), mode of inheritance: AD
• PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Chung-Jansen synrome (Developmental delay, intellectual disability, obesity, and dysmorphic features)	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	23033978; 27900362; 29209020

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PHIP gene.

• not provided (26 variants)
• PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome (23 variants)
• Inborn genetic diseases (4 variants)
• PHIP-related disorder (3 variants)
• Schizophrenia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHIP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	128	21	151
missense		20	222	15	14	271
nonsense	19	17	4			40
start loss						0
frameshift	26	13	2			41
inframe indel		3	4			7
splice donor/acceptor (+/-2bp)	7	13	2			22
splice region		4	24	36	3	67
non coding	1		6	77	59	143
Total	53	66	242	220	94

Highest pathogenic variant AF is 0.0000132

Variants in PHIP

This is a list of pathogenic ClinVar variants found in the PHIP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-78940496-TTA-T			Benign (Jun 20, 2021)
6-78940496-TTATA-T			Benign (Jun 20, 2021)
6-78940686-G-A		PHIP-related disorder	Likely benign (Aug 30, 2022)
6-78940694-T-C		PHIP-related disorder	Likely benign (Jan 21, 2024)
6-78940737-G-A			Uncertain significance (Aug 08, 2024)
6-78940743-G-A			Uncertain significance (Oct 30, 2023)
6-78940782-C-T			Uncertain significance (May 22, 2022)
6-78940786-C-T		PHIP-related disorder	Likely benign (Sep 06, 2023)
6-78940842-G-A			Conflicting classifications of pathogenicity (Sep 08, 2023)
6-78940848-G-C		not specified	Uncertain significance (Apr 25, 2024)
6-78940856-G-A			Uncertain significance (Nov 06, 2023)
6-78940868-G-A		PHIP-related disorder	Uncertain significance (May 16, 2024)
6-78940873-A-C			Likely benign (Apr 04, 2022)
6-78940890-C-A		PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome	Uncertain significance (May 12, 2022)
6-78940891-A-C			Uncertain significance (Aug 10, 2023)
6-78940896-C-G		Autism • PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome • Inborn genetic diseases • PHIP-related disorder	Conflicting classifications of pathogenicity (Nov 28, 2023)
6-78940904-T-A		PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome	Uncertain significance (Mar 02, 2021)
6-78940914-G-GATC			Uncertain significance (Jan 16, 2024)
6-78940922-A-G		PHIP-related disorder	Uncertain significance (Jan 16, 2024)
6-78940931-C-T		PHIP-related disorder	Uncertain significance (Oct 26, 2022)
6-78940932-G-A			Uncertain significance (Sep 15, 2024)
6-78940939-TCTC-T			Uncertain significance (Jan 21, 2024)
6-78940948-C-T			Likely benign (Apr 19, 2022)
6-78940950-C-T		PHIP-related disorder • not specified	Uncertain significance (Jun 24, 2024)
6-78940954-G-GA			Uncertain significance (Dec 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHIP	protein_coding	protein_coding	ENST00000275034	40	142370

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.64e-13	125732	0	12	125744	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.14	508	955	0.532	0.0000497	11924
Missense in Polyphen		162	471.6	0.34351		5877
Synonymous	0.297	308	315	0.979	0.0000158	3388
Loss of Function	8.93	6	105	0.0574	0.00000608	1255

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000725	0.0000703
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:12242307, ECO:0000269|PubMed:21834987}.

Recessive Scores

• pRec: 0.106

Intolerance Scores

• loftool: 0.444
• rvis_EVS: -1.24
• rvis_percentile_EVS: 5.49

Haploinsufficiency Scores

• pHI: 0.945
• hipred: Y
• hipred_score: 0.575
• ghis: 0.639

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.652

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Phip
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; liver/biliary system phenotype; respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of protein phosphorylation;regulation of transcription by RNA polymerase II;cytoskeleton organization;positive regulation of cell population proliferation;insulin receptor signaling pathway;regulation of cell shape;regulation of cell morphogenesis;negative regulation of apoptotic process;positive regulation of insulin-like growth factor receptor signaling pathway;positive regulation of mitotic nuclear division;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;negative regulation of extrinsic apoptotic signaling pathway
• Cellular component: nucleus
• Molecular function: insulin receptor binding;protein binding;lysine-acetylated histone binding