ZFYVE26

zinc finger FYVE-type containing 26, the group of Zinc fingers FYVE-type

Basic information

Region (hg38): 14:67727374-67816590

Previous symbols: [ "SPG15" ]

Links

ENSG00000072121

∙ NCBI:23503 ∙ OMIM:612012 ∙ HGNC:20761 ∙ Uniprot:Q68DK2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hereditary spastic paraplegia 15 (Definitive), mode of inheritance: AR
hereditary spastic paraplegia 15 (Definitive), mode of inheritance: AR
hereditary spastic paraplegia 15 (Strong), mode of inheritance: AR
hereditary spastic paraplegia 15 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 15, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	11342696; 14745065; 17661097; 19438933; 18394578; 19805727

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZFYVE26 gene.

Spastic paraplegia (147 variants)
Hereditary spastic paraplegia 15 (22 variants)
not provided (8 variants)
Hereditary spastic paraplegia (5 variants)
Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZFYVE26 gene is commonly pathogenic or not. These statistics are base on transcript: . Only rare variants are included in the table.

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			11 clinvar	910 clinvar	13 clinvar	934
missense	1 clinvar	1 clinvar	666 clinvar	23 clinvar	7 clinvar	698
nonsense	71 clinvar	66 clinvar	3 clinvar	1 clinvar		141
start loss	1		1			2
frameshift	80 clinvar	79 clinvar	3 clinvar			162
splice donor/acceptor (+/-2bp)	5 clinvar	56 clinvar	1 clinvar			62
Total	158	202	685	934	20

Highest pathogenic variant AF is 0.0000131553

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZFYVE26	protein_coding	protein_coding	ENST00000347230	41	89217

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.69e-23	1.00	125614	0	134	125748	0.000533

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.520	1280	1.33e+3	0.960	0.0000775	16499
Missense in Polyphen		314	382.62	0.82065		5122
Synonymous	0.511	521	536	0.972	0.0000301	5150
Loss of Function	5.23	58	120	0.484	0.00000624	1427

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000807	0.000807
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000435	0.000435
Finnish	0.000278	0.000277
European (Non-Finnish)	0.000688	0.000686
Middle Eastern	0.000435	0.000435
South Asian	0.000588	0.000588
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Phosphatidylinositol 3-phosphate-binding protein required for the abcission step in cytokinesis: recruited to the midbody during cytokinesis and acts as a regulator of abcission. May also be required for efficient homologous recombination DNA double-strand break repair. {ECO:0000269|PubMed:20208530}.;
Disease: DISEASE: Spastic paraplegia 15, autosomal recessive (SPG15) [MIM:270700]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG15 is a complex form associated with additional neurological symptoms such as cognitive deterioration or mental retardation, axonal neuropathy, mild cerebellar signs, and, less frequently, a central hearing deficit, decreased visual acuity, or retinal degeneration. {ECO:0000269|PubMed:18394578, ECO:0000269|PubMed:19084844, ECO:0000269|PubMed:19805727}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.105

Intolerance Scores

loftool: 0.892
rvis_EVS: -0.27
rvis_percentile_EVS: 33.59

Haploinsufficiency Scores

pHI: 0.0833
hipred: N
hipred_score: 0.466
ghis: 0.540

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.397

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Zfyve26
Phenotype: skeleton phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; growth/size/body region phenotype;

Zebrafish Information Network

Gene name: zfyve26
Affected structure: motor neuron
Phenotype tag: abnormal
Phenotype quality: branchiness

Gene ontology

Biological process: mitotic cytokinesis;double-strand break repair via homologous recombination;regulation of cytokinesis
Cellular component: lysosomal membrane;centrosome;midbody
Molecular function: protein binding;phosphatidylinositol-3-phosphate binding;metal ion binding