ANKFY1

protein-coding

ankyrin repeat and FYVE domain containing 1, the group of Zinc fingers FYVE-type|Ankyrin repeat domain containing|BTB domain containing

Gene summary

This gene encodes a cytoplasmic protein that contains a coiled-coil structure and a BTB/POZ domain at its N-terminus, ankyrin repeats in the middle portion, and a FYVE-finger motif at its C-terminus. This protein belongs to a subgroup of double zinc finger proteins which may be involved in vesicle or protein transport. Alternate splicing results in multiple transcript variants of this gene. [provided by RefSeq, Apr 2012]

MANE transcript

NM_001330063.2

Inheritance

AD, AR

ClinVar variants

U:168B:37

Top phenotype

familial idiopathic steroid-resistant nephrotic syndrome

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr17:4,163,821-4,263,995

External References & Databases

Ensembl (ENSG00000185722)

Transcript & Mutation Effects

hg38 • Region Span ~100.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial idiopathic steroid-resistant nephrotic syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019006

Submitter: Orphanet

kidney disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005240

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ANKFY1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 162

ANKFY1-related disorderTotal: 40

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001330063.2. 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				26 clinvar	3 clinvar	29
missense			163 clinvar	7 clinvar	1 clinvar	171
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	168	33	4	205

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001330063.2	RefSeq	NP_001316992.1	25	MANE Select
ENST00000341657.9	Ensembl	ENSP00000343362.4	25	MANE Select
NM_001257999.3	RefSeq	NP_001244928.1	25	Standard
NM_016376.5	RefSeq	NP_057460.3	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase

Biological Process

endocytosis
endosomal transport
endosomal vesicle fusion
retrograde transport, endosome to Golgi
positive regulation of pinocytosis

Molecular Function

protein binding
Rab GTPase binding
metal ion binding
phosphatidylinositol phosphate binding

Cellular Component

lysosomal membrane
endosome
early endosome
cytosol
endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000570535
Coding exons: 25
Length: 100074
Individuals with no LoFs: 124792
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 124814
p: 0.0000881

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.46	531	717	0.741	0.0000425	7906
Missense (PolyPhen)		157	270.48	0.58046		3015
Synonymous	1.02	283	306	0.926	0.0000204	2431
Loss of Function	5.74	11	58.3	0.189	0.00000316	653

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000093	0.000093	rare
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.000069	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Proposed effector of Rab5. Binds to phosphatidylinositol 3-phosphate (PI(3)P). Involved in homotypic early endosome fusion and to a lesser extent in heterotypic fusion of chlathrin-coated vesicles with early endosomes. Involved in macropinocytosis; the function is dependent on Rab5-GTP. Required for correct endosomal localization. Involved in the internalization and trafficking of activated tyrosine kinase receptors such as PDGFRB. Regulates the subcellular localization of the retromer complex in a EHD1- dependent manner. Involved in endosome-to-Golgi transport and biosynthetic transport to late endosomes and lysosomes indicative for a regulation of retromer complex-mediated retrograde transport. {ECO:0000269|PubMed:15328530, ECO:0000269|PubMed:22284051, ECO:0000269|PubMed:24102721}.;

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 0.491
RVIS EVS: -1.75
RVIS percentile EVS: 2.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.926

Gene Damage Prediction

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