PSD

protein-coding

pleckstrin and Sec7 domain containing, the group of Pleckstrin and Sec7 domain containing|Pleckstrin homology domain containing

Gene summary

This gene encodes a Plekstrin homology and SEC7 domains-containing protein that functions as a guanine nucleotide exchange factor. The encoded protein regulates signal transduction by activating ADP-ribosylation factor 6. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

MANE transcript

NM_002779.5

Inheritance

—

ClinVar variants

U:133B:18

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr10:102,402,617-102,421,539

External References & Databases

Ensembl (ENSG00000059915)

Transcript & Mutation Effects

hg38 • Region Span ~18.9 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 PSD variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 127

not providedTotal: 16

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002779.5. 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			3 clinvar	10 clinvar	2 clinvar	15
missense			125 clinvar	4 clinvar	2 clinvar	131
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	133	14	4	151

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002779.5	RefSeq	NP_002770.3	16	MANE Select
ENST00000020673.6	Ensembl	ENSP00000020673.5	16	MANE Select
NM_001270965.2	RefSeq	NP_001257894.1	16	Standard
NM_001270966.2	RefSeq	NP_001257895.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)

Biological Process

signal transduction
neuron projection development
regulation of ARF protein signal transduction

Molecular Function

ARF guanyl-nucleotide exchange factor activity
protein binding
phospholipid binding

Cellular Component

cleavage furrow
ruffle membrane
dendritic spine
extrinsic component of postsynaptic endosome membrane
postsynaptic density, intracellular component

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000020673
Coding exons: 16
Length: 18921
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.80	504	631	0.799	0.0000389	6501
Missense (PolyPhen)		170	271.95	0.62512		2786
Synonymous	0.140	260	263	0.989	0.0000158	2256
Loss of Function	4.93	8	42.8	0.187	0.00000252	462

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000049	0.000046	rare
European (Non-Finnish)	0.000072	0.000070	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide exchange factor for ARF6 (PubMed:23603394). Induces cytoskeletal remodeling (By similarity). {ECO:0000250|UniProtKB:Q5DTT2, ECO:0000269|PubMed:23603394}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.394
RVIS EVS: -1.32
RVIS percentile EVS: 4.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.849

Gene Damage Prediction

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