SH3PXD2A

protein-coding

SH3 and PX domains 2A

Gene summary

Predicted to enable superoxide-generating NADPH oxidase activator activity. Involved in osteoclast fusion and superoxide metabolic process. Located in podosome. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

SH3MD1

MANE transcript

NM_001394015.1

Inheritance

—

ClinVar variants

U:174B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr10:103,594,027-103,855,584

External References & Databases

Ensembl (ENSG00000107957)

Transcript & Mutation Effects

hg38 • Region Span ~261.6 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 SH3PXD2A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 174

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001394015.1. 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		2 clinvar	3
missense			170 clinvar	5 clinvar	3 clinvar	178
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	174	5	5	184

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001394015.1	RefSeq	NP_001380944.1	15	MANE Select
ENST00000369774.9	Ensembl	ENSP00000358789.4	15	MANE Select
NM_001365079.1	RefSeq	NP_001352008.1	9	Standard
NM_001394016.1	RefSeq	NP_001380945.1	10	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sh3pxd2aa	Danio rerio	Structure: neural crest cell Quality: increased amount abnormal

Gene / Model

Organism

Observed Phenotype

sh3pxd2aa

Danio rerio

Structure: neural crest cell

Quality: increased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Invadopodia formation
Extracellular matrix organization

Biological Process

superoxide metabolic process
extracellular matrix organization
positive regulation of catalytic activity
osteoclast fusion

Molecular Function

protease binding
protein binding
phosphatidylinositol-4,5-bisphosphate binding
phosphatidylinositol-5-phosphate binding
superoxide-generating NADPH oxidase activator activity

Cellular Component

podosome
cytosol
cell junction
cell projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355946
Coding exons: 14
Length: 267017
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.56	561	675	0.831	0.0000435	7112
Missense (PolyPhen)		260	344.45	0.75482		3632
Synonymous	0.294	292	298	0.978	0.0000209	2265
Loss of Function	5.42	8	48.8	0.164	0.00000243	557

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00018	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00013	0.000092	rare
European (Non-Finnish)	0.000075	0.000062	rare
South Asian	0.000037	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Adapter protein involved in invadopodia and podosome formation, extracellular matrix degradation and invasiveness of some cancer cells. Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. In association with ADAM12, mediates the neurotoxic effect of amyloid-beta peptide. {ECO:0000269|PubMed:12615925, ECO:0000269|PubMed:15710328, ECO:0000269|PubMed:15710903, ECO:0000269|PubMed:19755710, ECO:0000269|PubMed:20609497}.;

Recessive Scores

pRec: 0.121

Intolerance Scores

LoFtool: 0.386
RVIS EVS: -1.83
RVIS percentile EVS: 2.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.751

Gene Damage Prediction

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