ZFYVE27

zinc finger FYVE-type containing 27, the group of Zinc fingers FYVE-type

Basic information

Region (hg38): 10:97737121-97760907

Links

ENSG00000155256 ∙ NCBI:118813 ∙ OMIM:610243 ∙ HGNC:26559 ∙ Uniprot:Q5T4F4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spastic paraplegia 33 (Limited), mode of inheritance: AD
• hereditary spastic paraplegia 33 (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 33, autosomal dominant	AD	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	16826525; 18606302

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZFYVE27 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZFYVE27 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	15	2	18
missense			62	6	5	73
nonsense						0
start loss			1			1
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)		1	4			5
splice region			1		2	3
non coding			25	12	45	82
Total	0	1	95	33	52

Variants in ZFYVE27

This is a list of pathogenic ClinVar variants found in the ZFYVE27 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-97738467-A-G		Hereditary spastic paraplegia 33	Uncertain significance (Jan 13, 2018)
10-97738477-G-A		Hereditary spastic paraplegia 33 • Spastic paraplegia	Benign (Nov 22, 2022)
10-97738480-G-T			Uncertain significance (Jan 01, 2024)
10-97738495-T-C		Spastic paraplegia	Likely benign (Jul 03, 2023)
10-97738509-C-T		Hereditary spastic paraplegia 33 • Spastic paraplegia	Benign (Dec 21, 2023)
10-97738514-C-G		Hereditary spastic paraplegia 33	Likely benign (Jan 13, 2018)
10-97738526-G-A		not specified • Spastic paraplegia	Uncertain significance (Jan 23, 2024)
10-97738530-T-C		Spastic paraplegia	Uncertain significance (Aug 17, 2023)
10-97738539-C-T		Spastic paraplegia • Hereditary spastic paraplegia 33 • not specified	Benign/Likely benign (Jan 18, 2024)
10-97738556-C-G		Hereditary spastic paraplegia 33 • Spastic paraplegia	Benign (Feb 08, 2023)
10-97738574-C-T		not specified	Uncertain significance (Dec 27, 2023)
10-97738578-C-T		not specified	Uncertain significance (May 30, 2023)
10-97738603-C-T		Hereditary spastic paraplegia 33 • not specified • Spastic paraplegia	Benign/Likely benign (Jan 24, 2024)
10-97738626-A-G		Spastic paraplegia • Hereditary spastic paraplegia 33 • not specified	Uncertain significance (Oct 17, 2023)
10-97738634-C-T		Spastic paraplegia • not specified	Conflicting classifications of pathogenicity (Jul 21, 2022)
10-97738664-T-C		Spastic paraplegia	Uncertain significance (Nov 22, 2023)
10-97738682-C-T		Hereditary spastic paraplegia 33	Uncertain significance (Jan 12, 2018)
10-97743093-G-A		Spastic paraplegia	Uncertain significance (Aug 19, 2023)
10-97743115-C-G		Hereditary spastic paraplegia 33	Uncertain significance (Jan 12, 2018)
10-97743130-G-C		Spastic paraplegia	Likely benign (Aug 28, 2022)
10-97743134-C-T		Spastic paraplegia	Benign (Nov 19, 2023)
10-97743138-A-G		Spastic paraplegia • not specified	Uncertain significance (Sep 27, 2022)
10-97743140-G-A		not specified • Hereditary spastic paraplegia 33 • Spastic paraplegia	Benign (Jan 25, 2024)
10-97743155-TTGAA-T			Uncertain significance (Sep 05, 2017)
10-97744713-G-A		Spastic paraplegia	Benign (Dec 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZFYVE27	protein_coding	protein_coding	ENST00000356257	12	23787

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.06e-9	0.521	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.818	210	246	0.853	0.0000156	2685
Missense in Polyphen		73	78.583	0.92896		741
Synonymous	-0.288	109	105	1.04	0.00000695	835
Loss of Function	1.16	17	23.0	0.739	0.00000123	269

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000327	0.000327
Ashkenazi Jewish	0.00	0.00
East Asian	0.000435	0.000435
Finnish	0.000511	0.000508
European (Non-Finnish)	0.000168	0.000167
Middle Eastern	0.000435	0.000435
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key regulator of RAB11-dependent vesicular trafficking during neurite extension through polarized membrane transport (PubMed:17082457). Promotes axonal elongation and contributes to the establishment of neuronal cell polarity (By similarity). Involved in nerve growth factor-induced neurite formation in VAPA- dependent manner (PubMed:19289470). Contributes to both the formation and stabilization of the tubular ER network (PubMed:24668814). Involved in ER morphogenesis by regulating the sheet-to-tubule balance and possibly the density of tubule interconnections (PubMed:23969831). Acts as an adapter protein and facilitates the interaction of KIF5A with VAPA, VAPB, SURF4, RAB11A, RAB11B and RTN3 and the ZFYVE27-KIF5A complex contributes to the transport of these proteins in neurons. Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a KIF5A/B-dependent manner (PubMed:21976701). {ECO:0000250|UniProtKB:Q3TXX3, ECO:0000269|PubMed:17082457, ECO:0000269|PubMed:19289470, ECO:0000269|PubMed:21976701, ECO:0000269|PubMed:23969831, ECO:0000269|PubMed:24668814}.
• Disease: DISEASE: Spastic paraplegia 33, autosomal dominant (SPG33) [MIM:610244]: 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. {ECO:0000269|PubMed:16826525, ECO:0000269|PubMed:18606302, ECO:0000269|PubMed:23969831, ECO:0000269|PubMed:24668814}. Note=The disease is caused by mutations affecting the gene represented in this entry. According to PubMed:18606302, the properties of the variant Val-191 and its frequency in some populations raise doubts on the implication of that gene in the disease.
• Pathway: Endocytosis - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.350
• rvis_EVS: 0.87
• rvis_percentile_EVS: 88.8

Haploinsufficiency Scores

• pHI: 0.140
• hipred: Y
• hipred_score: 0.605
• ghis: 0.442

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.443

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zfyve27

Zebrafish Information Network

• Gene name: zfyve27
• Affected structure: primary motor neuron
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: vesicle-mediated transport;neuron projection development;positive regulation of axon extension;neurotrophin TRK receptor signaling pathway;endoplasmic reticulum tubular network formation;protein localization to plasma membrane
• Cellular component: nucleoplasm;endoplasmic reticulum;cytosol;integral component of membrane;integral component of endoplasmic reticulum membrane;axon;dendrite;growth cone membrane;recycling endosome membrane;endoplasmic reticulum tubular network
• Molecular function: protein binding;protein self-association;metal ion binding