PHACTR4

protein-coding

phosphatase and actin regulator 4, the group of Protein phosphatase 1 regulatory subunits|Phosphatase and actin regulators

Gene summary

This gene encodes a member of the phosphatase and actin regulator (PHACTR) family. Other PHACTR family members have been shown to inhibit protein phosphatase 1 (PP1) activity, and the homolog of this gene in the mouse has been shown to interact with actin and PP1. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001048183.3

Inheritance

—

ClinVar variants

U:101B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr1:28,369,582-28,500,364

External References & Databases

Ensembl (ENSG00000204138)

Transcript & Mutation Effects

hg38 • Region Span ~130.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PHACTR4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 97

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001048183.3. 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			1 clinvar			1
missense			95 clinvar	5 clinvar		100
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	101	5	0	106

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001048183.3	RefSeq	NP_001041648.1	13	MANE Select
ENST00000373839.8	Ensembl	ENSP00000362945.3	13	MANE Select
NM_001350158.2	RefSeq	NP_001337087.1	14	Standard
NM_001350159.2	RefSeq	NP_001337088.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

neural crest cell migration
neural tube closure
Rho protein signal transduction
actin cytoskeleton organization
positive regulation of catalytic activity

Molecular Function

actin binding
protein phosphatase 1 binding
protein phosphatase activator activity

Cellular Component

cytoplasm
lamellipodium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373836
Coding exons: 13
Length: 130768
Individuals with no LoFs: 124775
Homozygous LoFs: 1
Heterozygous LoFs: 34
Defined: 124810
p: 0.000140

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.10	334	396	0.844	0.0000212	4635
Missense (PolyPhen)		103	137.67	0.74814		1599
Synonymous	0.987	126	141	0.894	0.00000750	1429
Loss of Function	2.97	15	33.5	0.447	0.00000202	387

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00019	rare
Latino/Admixed American	0.000092	0.000087	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.00016	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulator of protein phosphatase 1 (PP1) required for neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. Acts as an activator of PP1 by interacting with PPP1CA and preventing phosphorylation of PPP1CA at 'Thr-320'. During neural tube closure, localizes to the ventral neural tube and activates PP1, leading to down-regulate cell proliferation within cranial neural tissue and the neural retina. Also acts as a regulator of migration of enteric neural crest cells (ENCCs) by activating PP1, leading to dephosphorylation and subsequent activation of cofilin (COF1 or COF2) and repression of the integrin signaling through the RHO/ROCK pathway (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0662

Intolerance Scores

LoFtool: 0.862
RVIS EVS: -0.44
RVIS percentile EVS: 24.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.202

Gene Damage Prediction

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