SYNPO2

synaptopodin 2, the group of PDZ domain containing

Basic information

Region (hg38): 4:118850688-119061247

Links

ENSG00000172403 ∙ NCBI:171024 ∙ ∙ HGNC:17732 ∙ Uniprot:Q9UMS6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SYNPO2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SYNPO2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	3	4
missense			75		3	78
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	75	1	6

Variants in SYNPO2

This is a list of pathogenic ClinVar variants found in the SYNPO2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-118889054-T-A		not specified	Uncertain significance (Oct 20, 2021)
4-118889104-G-A		not specified	Uncertain significance (Mar 21, 2022)
4-119023575-T-C		not specified	Uncertain significance (Apr 20, 2024)
4-119026697-G-T		not specified	Uncertain significance (Nov 30, 2022)
4-119026837-G-C		not specified	Uncertain significance (Jun 18, 2021)
4-119026867-G-C		not specified	Uncertain significance (Mar 02, 2023)
4-119026961-G-C		not specified	Uncertain significance (May 23, 2023)
4-119026976-C-G		not specified	Uncertain significance (Feb 22, 2024)
4-119026984-G-T		not specified	Uncertain significance (Feb 22, 2024)
4-119027015-G-A		not specified	Uncertain significance (Dec 20, 2023)
4-119027214-C-T		not specified	Uncertain significance (Aug 15, 2023)
4-119027226-T-C		not specified	Uncertain significance (Apr 13, 2023)
4-119027228-A-C		not specified	Uncertain significance (Jan 24, 2024)
4-119027238-G-A		not specified	Uncertain significance (Jan 27, 2022)
4-119027357-T-C		not specified	Uncertain significance (Feb 11, 2022)
4-119027358-C-T		not specified	Uncertain significance (Mar 08, 2024)
4-119027373-A-G		not specified	Uncertain significance (Oct 12, 2021)
4-119027388-G-A		not specified	Uncertain significance (Jun 22, 2024)
4-119027416-C-A		not specified	Uncertain significance (Jun 03, 2024)
4-119029851-G-A		not specified	Uncertain significance (Dec 27, 2022)
4-119029914-C-T		not specified	Uncertain significance (Mar 25, 2024)
4-119029933-T-G			Benign (Jan 30, 2018)
4-119029937-A-T		not specified	Uncertain significance (Mar 16, 2022)
4-119029976-C-T		not specified	Uncertain significance (Jan 24, 2023)
4-119029980-G-A		not specified	Uncertain significance (May 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SYNPO2	protein_coding	protein_coding	ENST00000307142	5	172407

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.56e-8	1.00	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0390	688	691	0.996	0.0000376	8125
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000354	0.000354
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000326	0.000217
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000152	0.000149
Middle Eastern	0.000326	0.000217
South Asian	0.000134	0.000131
Other	0.00	0.00

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.256
• hipred: N
• hipred_score: 0.384
• ghis: 0.524

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.179

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Synpo2
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: autophagosome assembly;positive regulation of actin filament bundle assembly;chaperone-mediated autophagy
• Cellular component: stress fiber;nucleus;cytosol;focal adhesion;actin cytoskeleton;Z disc;intracellular membrane-bounded organelle;tethering complex
• Molecular function: actin binding;protein binding;protein binding, bridging;filamin binding;muscle alpha-actinin binding;alpha-actinin binding;14-3-3 protein binding