PACSIN2

protein-coding

protein kinase C and casein kinase substrate in neurons 2, the group of F-BAR domain containing

Gene summary

This gene is a member of the protein kinase C and casein kinase substrate in neurons family. The encoded protein is involved in linking the actin cytoskeleton with vesicle formation by regulating tubulin polymerization. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

MANE transcript

NM_001184970.3

Inheritance

—

ClinVar variants

U:60B:2

Top phenotype

Myoepithelial tumor

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr22:42,835,412-43,015,149

External References & Databases

Ensembl (ENSG00000100266)

Transcript & Mutation Effects

hg38 • Region Span ~179.7 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 PACSIN2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 55

not providedTotal: 1

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001184970.3. 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 clinvar		2
missense			58 clinvar	1 clinvar		59
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	60	2	0	62

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 71 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001184970.3	RefSeq	NP_001171899.1	10	MANE Select
ENST00000263246.8	Ensembl	ENSP00000263246.3	10	MANE Select
NM_001184971.1	RefSeq	NP_001171900.1	9	Standard
NM_001349968.1	RefSeq	NP_001336897.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
Clathrin-mediated endocytosis

Biological Process

cytoskeleton organization
actin cytoskeleton organization
protein localization to endosome
negative regulation of endocytosis
cell projection morphogenesis

Molecular Function

transporter activity
protein binding
phospholipid binding
cytoskeletal protein binding
identical protein binding

Cellular Component

cytoplasm
early endosome
cytosol
cytoskeleton
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263246
Coding exons: 10
Length: 179734
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125740
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.30	248	313	0.793	0.0000202	3243
Missense (PolyPhen)		86	120.78	0.71205		1249
Synonymous	-0.346	140	135	1.04	0.0000101	853
Loss of Function	3.78	7	28.9	0.242	0.00000157	299

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	0.00011	0.00011	rare
Finnish	0.00051	0.00051	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Lipid-binding protein that is able to promote the tubulation of the phosphatidic acid-containing membranes it preferentially binds. Plays a role in intracellular vesicle- mediated transport. Involved in the endocytosis of cell-surface receptors like the EGF receptor, contributing to its internalization in the absence of EGF stimulus. May also play a role in the formation of caveolae at the cell membrane. Recruits DNM2 to caveolae, and thereby plays a role in caveola-mediated endocytosis. {ECO:0000269|PubMed:21610094, ECO:0000269|PubMed:21693584, ECO:0000269|PubMed:23129763, ECO:0000269|PubMed:23236520, ECO:0000269|PubMed:23596323}.;

Recessive Scores

pRec: 0.207

Intolerance Scores

LoFtool: 0.405
RVIS EVS: 0.04
RVIS percentile EVS: 57.41

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.736

Gene Damage Prediction

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