ZFYVE26

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

Basic information

Region (hg38): 14:67727373-67816590

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 (1825 variants)
• Hereditary spastic paraplegia 15 (432 variants)
• not provided (389 variants)
• Hereditary spastic paraplegia (117 variants)
• Inborn genetic diseases (99 variants)
• not specified (75 variants)
• Spastic Paraplegia, Recessive (4 variants)
• Abnormal central motor function (3 variants)
• Tip-toe gait (3 variants)
• Atypical behavior;Intellectual disability;Spastic paraplegia (1 variants)
• See cases (1 variants)
• ZFYVE26-related condition (1 variants)
• Retinal dystrophy (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.

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			12	756	13	781
missense	1	1	602	22	7	633
nonsense	63	58	3			124
start loss	1		1			2
frameshift	72	72	3			147
inframe indel			18			18
splice donor/acceptor (+/-2bp)	4	48				52
splice region			26	97		123
non coding			37	235	92	364
Total	141	179	676	1013	112

Highest pathogenic variant AF is 0.0000197

Variants in ZFYVE26

This is a list of pathogenic ClinVar variants found in the ZFYVE26 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-67727373-AG-A			Benign (May 23, 2021)
14-67727376-G-C			Benign (May 14, 2021)
14-67727476-G-T			Benign (Jun 19, 2021)
14-67729171-T-C		Leber congenital amaurosis 13	Likely benign (Jul 25, 2023)
14-67729175-G-A		Leber congenital amaurosis 13	Likely benign (Dec 19, 2022)
14-67729176-C-A		Leber congenital amaurosis 13	Likely benign (Jul 22, 2021)
14-67729177-C-T		Leber congenital amaurosis 13	Likely benign (Jul 28, 2023)
14-67729177-CCT-C		Leber congenital amaurosis 13	Likely benign (Oct 27, 2023)
14-67729179-T-C		Retinitis Pigmentosa, Recessive • Leber congenital amaurosis 13 • Retinitis pigmentosa	Conflicting classifications of pathogenicity (Jan 31, 2024)
14-67729180-C-T		Leber congenital amaurosis 13	Likely benign (May 21, 2023)
14-67729181-T-C		Leber congenital amaurosis 13	Likely benign (Aug 18, 2023)
14-67729182-T-C		Leber congenital amaurosis 13	Likely benign (Nov 07, 2022)
14-67729184-G-C		Leber congenital amaurosis 13	Likely benign (Jan 24, 2023)
14-67729188-C-T		Leber congenital amaurosis 13	Uncertain significance (Aug 19, 2022)
14-67729189-A-C		Leber congenital amaurosis 13	Likely pathogenic (Oct 14, 2021)
14-67729189-A-T		Leber congenital amaurosis 13	Likely pathogenic (Aug 30, 2023)
14-67729190-G-A		Leber congenital amaurosis 13	Likely pathogenic (Aug 21, 2022)
14-67729192-C-A		Leber congenital amaurosis 13	Likely benign (Apr 26, 2023)
14-67729194-C-T		Retinitis Pigmentosa, Recessive • Leber congenital amaurosis 13 • Retinitis pigmentosa • Leber congenital amaurosis • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 31, 2024)
14-67729195-C-A		Leber congenital amaurosis 13	Uncertain significance (May 20, 2023)
14-67729195-C-T		Leber congenital amaurosis 13	Likely benign (Dec 04, 2023)
14-67729196-G-A		Leber congenital amaurosis 13	Uncertain significance (Jun 01, 2022)
14-67729196-G-T		Leber congenital amaurosis 13	Uncertain significance (Nov 12, 2022)
14-67729199-G-T		Retinal dystrophy • Leber congenital amaurosis	Conflicting classifications of pathogenicity (Oct 30, 2023)
14-67729200-T-A		Retinal dystrophy	Uncertain significance (Oct 01, 2023)

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