PPEF2

protein-coding

protein phosphatase with EF-hand domain 2, the group of EF-hand domain containing|Protein phosphatase catalytic subunits

Gene summary

This gene encodes a member of the serine/threonine protein phosphatase with EF-hand motif family. The protein contains a protein phosphatase catalytic domain, and at least two EF-hand calcium-binding motifs in its C terminus. Although its substrate(s) is unknown, the encoded protein, which is expressed specifically in photoreceptors and the pineal, has been suggested to play a role in the visual system. This gene shares high sequence similarity with the Drosophila retinal degeneration C (rdgC) gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006239.3

Inheritance

—

ClinVar variants

U:117B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr4:75,859,864-75,902,571

External References & Databases

Ensembl (ENSG00000156194)

Transcript & Mutation Effects

hg38 • Region Span ~42.7 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 PPEF2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 117

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006239.3. 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	3 clinvar		4
missense			115 clinvar	4 clinvar		119
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	117	7	0	124

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006239.3	RefSeq	NP_006230.2	16	MANE Select
ENST00000286719.12	Ensembl	ENSP00000286719.6	16	MANE Select
ENST00000511880.7	Ensembl	ENSP00000426186.2	5	Standard
ENST00000652700.1	Ensembl	ENSP00000498558.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein dephosphorylation
visual perception
negative regulation of peptidyl-threonine phosphorylation
regulation of MAP kinase activity
negative regulation of MAPK cascade

Molecular Function

protein serine/threonine phosphatase activity
iron ion binding
calcium ion binding
manganese ion binding
Hsp70 protein binding

Cellular Component

photoreceptor outer segment
photoreceptor inner segment
nucleus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000286719
Coding exons: 16
Length: 42705
Individuals with no LoFs: 117862
Homozygous LoFs: 140
Heterozygous LoFs: 7746
Defined: 125748
p: 0.0319

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0442	434	437	0.994	0.0000251	4950
Missense (PolyPhen)		162	164.57	0.98441		1998
Synonymous	-0.683	176	165	1.07	0.00000926	1416
Loss of Function	1.73	28	39.8	0.704	0.00000207	450

Population LoF Frequency

Population	CAF	p-value	Status
African	0.062	0.062	notable
Latino/Admixed American	0.033	0.028	notable
Ashkenazi Jewish	0.043	0.039	notable
East Asian	0.0035	0.0031	notable
Finnish	0.032	0.031	notable
European (Non-Finnish)	0.041	0.039	notable
South Asian	0.013	0.011	notable
Other	0.037	0.033	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in phototransduction. May dephosphorylate photoactivated rhodopsin. May function as a calcium sensing regulator of ionic currents, energy production or synaptic transmission.;

Recessive Scores

pRec: 0.0896

Intolerance Scores

LoFtool: 0.831
RVIS EVS: 1.16
RVIS percentile EVS: 92.66

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.794

Gene Damage Prediction

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