PHACTR1

protein-coding

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

Gene summary

The protein encoded by this gene is a member of the phosphatase and actin regulator family of proteins. This family member can bind actin and regulate the reorganization of the actin cytoskeleton. It plays a role in tubule formation and in endothelial cell survival. Polymorphisms in this gene are associated with susceptibility to myocardial infarction, coronary artery disease and cervical artery dissection. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]

Previous symbols:

RPEL1

MANE transcript

NM_030948.6

Inheritance

ClinVar variants

P:8U:101B:43

Top phenotype

Developmental and epileptic encephalopathy 70

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr6:12,716,312-13,290,446

External References & Databases

Ensembl (ENSG00000112137)

Transcript & Mutation Effects

hg38 • Region Span ~574.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental and epileptic encephalopathy, 70STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032663

Submitter: G2P

developmental and epileptic encephalopathy, 70STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032663

Submitter: Labcorp Genetics (formerly Invitae)

developmental and epileptic encephalopathy, 70STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032663

Submitter: PanelApp Australia

developmental and epileptic encephalopathy, 70STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032663

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Developmental and epileptic encephalopathy 70AD

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 23033978; 30256902

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PHACTR1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 98

not providedTotal: 74

Developmental and epileptic encephalopathy, 70Total: 38

PHACTR1-related disorderTotal: 30

SchizophreniaTotal: 1

Neurodevelopmental abnormalityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030948.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	36 clinvar	1 clinvar	39
missense	3 clinvar	5 clinvar	86 clinvar	6 clinvar		100
nonsense			3 clinvar			3
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	3	5	101	42	1	152

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030948.6	RefSeq	NP_112210.1	13	MANE Select
ENST00000332995.12	Ensembl	ENSP00000329880.8	13	MANE Select
NM_001242648.4	RefSeq	NP_001229577.1	13	Standard
NM_001322308.3	RefSeq	NP_001309237.1	13	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
phactr1	Danio rerio	Structure: hepatic portal vein Quality: disorganized abnormal

Gene / Model

Organism

Observed Phenotype

phactr1

Danio rerio

Structure: hepatic portal vein

Quality: disorganized

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

actomyosin structure organization
actin cytoskeleton reorganization
negative regulation of phosphoprotein phosphatase activity
stress fiber assembly
cell motility

Molecular Function

actin binding
protein phosphatase inhibitor activity
protein phosphatase 1 binding

Cellular Component

nucleus
cytosol
cell junction
synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379348
Coding exons: 3
Length: 570753
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.708	73	92.1	0.792	0.00000430	1064
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.734

Gene Damage Prediction

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