PSD3

protein-coding

pleckstrin and Sec7 domain containing 3, the group of Pleckstrin and Sec7 domain containing|Pleckstrin homology domain containing

Gene summary

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in vesicle-mediated transport. Predicted to be located in membrane. Predicted to be active in glutamatergic synapse; postsynapse; and ruffle membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_015310.4

Inheritance

—

ClinVar variants

U:100B:17

Top phenotype

PSD3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr8:18,527,303-19,084,730

External References & Databases

Ensembl (ENSG00000156011)

Transcript & Mutation Effects

hg38 • Region Span ~557.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

antecubital pterygium syndromeLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0008339

Submitter: ClinGen

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PSD3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 92

not providedTotal: 16

PSD3-related disorderTotal: 6

Flexion contractureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015310.4. 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	3 clinvar	7
missense			96 clinvar	4 clinvar	7 clinvar	107
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	100	7	10	117

Loading ClinVar variants...

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_015310.4	RefSeq	NP_056125.3	16	MANE Select
ENST00000327040.13	Ensembl	ENSP00000324127.8	16	MANE Select
NM_001362819.2	RefSeq	NP_001349748.1	15	Standard
NM_001412865.1	RefSeq	NP_001399794.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)

Biological Process

regulation of ARF protein signal transduction

Molecular Function

ARF guanyl-nucleotide exchange factor activity

Cellular Component

postsynaptic density
cell junction
ruffle membrane
postsynaptic membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000327040
Coding exons: 16
Length: 557430
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125745
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.50	666	566	1.18	0.0000299	6859
Missense (PolyPhen)		196	216.67	0.90462		2601
Synonymous	-3.57	283	216	1.31	0.0000125	2004
Loss of Function	4.55	13	46.4	0.280	0.00000233	611

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000062	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide exchange factor for ARF6. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.500
RVIS EVS: 0.1
RVIS percentile EVS: 60.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.787

Gene Damage Prediction

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