PHACTR1

phosphatase and actin regulator 1, the group of Phosphatase and actin regulators

Basic information

Region (hg38): 6:12716311-13290446

Previous symbols: [ "RPEL1" ]

Links

ENSG00000112137 ∙ NCBI:221692 ∙ OMIM:608723 ∙ HGNC:20990 ∙ Uniprot:Q9C0D0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• West syndrome (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 70 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 70	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	Neurologic	23033978; 30256902

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PHACTR1 gene.

• not provided (21 variants)
• Developmental and epileptic encephalopathy, 70 (18 variants)
• Inborn genetic diseases (13 variants)
• PHACTR1-related condition (3 variants)
• not specified (2 variants)
• Global developmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHACTR1 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				9	2	11
missense	1	1	28	1		31
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region					1	1
non coding			5	2	5	12
Total	1	1	34	12	7

Variants in PHACTR1

This is a list of pathogenic ClinVar variants found in the PHACTR1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-12749703-A-G		Developmental and epileptic encephalopathy, 70	Uncertain significance (Apr 09, 2021)
6-12749704-T-C		not specified	Uncertain significance (Aug 08, 2022)
6-12749730-C-G		Developmental and epileptic encephalopathy, 70	Likely pathogenic (Feb 09, 2024)
6-12749731-G-T		not specified	Uncertain significance (Sep 14, 2023)
6-12749741-C-T		PHACTR1-related disorder	Likely benign (Apr 01, 2024)
6-12749746-C-A		Developmental and epileptic encephalopathy, 70	Uncertain significance (Oct 17, 2019)
6-12749749-C-G		Developmental and epileptic encephalopathy, 70	Likely pathogenic (Sep 07, 2023)
6-12749781-C-A		PHACTR1-related disorder	Uncertain significance (May 12, 2023)
6-12758714-C-G		Developmental and epileptic encephalopathy, 70	Uncertain significance (Jun 26, 2020)
6-12903725-A-G			Benign (Aug 23, 2019)
6-12933680-G-A			Benign (Dec 01, 2023)
6-12933813-C-T			Likely benign (Apr 01, 2024)
6-13013945-G-T		Developmental and epileptic encephalopathy, 70	Uncertain significance (Mar 25, 2024)
6-13014006-G-A			Likely benign (May 01, 2023)
6-13014007-C-A			Benign (May 01, 2023)
6-13014030-G-T			Benign (Dec 01, 2022)
6-13014106-A-G			Uncertain significance (Jul 01, 2022)
6-13053389-C-T		Developmental and epileptic encephalopathy, 70	Uncertain significance (Feb 05, 2021)
6-13053408-C-T		PHACTR1-related disorder	Likely benign (Jun 18, 2021)
6-13053411-C-T		PHACTR1-related disorder	Likely benign (Nov 01, 2022)
6-13053521-C-G		not specified	Uncertain significance (May 24, 2023)
6-13053521-C-T		not specified	Uncertain significance (Dec 19, 2023)
6-13160234-G-A		not specified	Uncertain significance (Jun 18, 2021)
6-13160258-G-A		not specified	Uncertain significance (May 04, 2023)
6-13160278-G-A			Uncertain significance (Dec 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHACTR1	protein_coding	protein_coding	ENST00000379348	3	570753

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.635	0.338	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.708	73	92.1	0.792	0.00000430	1064
Missense in Polyphen		1	2.2954	0.43565		27
Synonymous	0.398	34	37.1	0.917	0.00000178	360
Loss of Function	1.67	0	3.23	0.00	1.35e-7	48

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds actin monomers (G actin) and plays a role in the reorganization of the actin cytoskeleton and in formation of actin stress fibers. Plays a role in cell motility. Plays a role in the formation of tubules by endothelial cells. Regulates PPP1CA activity. Required for normal cell survival. {ECO:0000269|PubMed:21798305, ECO:0000269|PubMed:21939755}.

Recessive Scores

• pRec: 0.111

Haploinsufficiency Scores

• pHI: 0.557
• hipred: N
• hipred_score: 0.210
• ghis: 0.544

Essentials

• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.734

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Phactr1

Zebrafish Information Network

• Gene name: phactr1
• Affected structure: hepatic portal vein
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: actomyosin structure organization;actin cytoskeleton reorganization;negative regulation of phosphoprotein phosphatase activity;stress fiber assembly;cell motility
• Cellular component: nucleus;cytosol;cell junction;synapse
• Molecular function: actin binding;protein phosphatase inhibitor activity;protein phosphatase 1 binding