SYNPO2

protein-coding

synaptopodin 2, the group of PDZ domain containing

Gene summary

Enables alpha-actinin binding activity and filamin binding activity. Involved in obsolete regulation of Rho-dependent protein serine/threonine kinase activity; positive regulation of actin filament bundle assembly; and positive regulation of cell migration. Located in Z disc; focal adhesion; and stress fiber. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_133477.3

Inheritance

—

ClinVar variants

U:187B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr4:118,850,688-119,061,247

External References & Databases

Ensembl (ENSG00000172403)

Transcript & Mutation Effects

hg38 • Region Span ~210.6 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 SYNPO2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 186

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_133477.3. 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			2 clinvar	1 clinvar	3 clinvar	6
missense			185 clinvar	4 clinvar	3 clinvar	192
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	187	5	6	198

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_133477.3	RefSeq	NP_597734.2	5	MANE Select
ENST00000307142.9	Ensembl	ENSP00000306015.4	5	MANE Select
NM_001128933.3	RefSeq	NP_001122405.1	4	Standard
NM_001128934.3	RefSeq	NP_001122406.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

autophagosome assembly
positive regulation of actin filament bundle assembly
chaperone-mediated autophagy

Molecular Function

actin binding
protein binding
protein binding, bridging
filamin binding
muscle alpha-actinin binding

Cellular Component

stress fiber
nucleus
cytosol
focal adhesion
actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000307142
Coding exons: 5
Length: 172407
Individuals with no LoFs: 125708
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125748
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0390	688	691	0.996	0.0000376	8125
Missense (PolyPhen)		188	225.11	0.83514		2711
Synonymous	0.313	272	279	0.976	0.0000172	2662
Loss of Function	3.57	20	46.2	0.433	0.00000288	523

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00033	0.00022	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has an actin-binding and actin-bundling activity. Can induce the formation of F-actin networks in an isoform-specific manner (PubMed:24005909, PubMed:23225103). At the sarcomeric Z lines is proposed to act as adapter protein that links nascent myofibers to the sarcolemma via ZYX and may play a role in early assembly and stabilization of the Z lines. Involved in autophagosome formation. May play a role in chaperone-assisted selective autophagy (CASA) involved in Z lines maintenance in striated muscle under mechanical tension; may link the client- processing CASA chaperone machinery to a membrane-tethering and fusion complex providing autophagosome membranes (By similarity). Involved in regulation of cell migration (PubMed:22915763, PubMed:25883213). May be a tumor suppressor (PubMed:16885336). {ECO:0000250|UniProtKB:D4A702, ECO:0000250|UniProtKB:Q91YE8, ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:23225103, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213, ECO:0000305|PubMed:16885336, ECO:0000305|PubMed:20554076}.; FUNCTION: Isoform 2: Involved in regulation of cell migration. Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: Isoform 4: Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:24005909}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.580
RVIS EVS: -0.23
RVIS percentile EVS: 36.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.179

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High