FYCO1

protein-coding

FYVE and coiled-coil domain autophagy adaptor 1, the group of Zinc fingers FYVE-type|GOLD domain containing

Gene summary

The gene encodes a Rab7 adapter protein that is implicated in the microtubule transport of autophagosomes. The encoded protein contains a RUN domain, a FYVE-type zinc finger domain, and Golgi dynamics (GOLD) domain. The encoded protein plays a role in microtubule plus end-directed transport of autophagic vesicles through interactions with the small GTPase Rab7, phosphatidylinositol-3-phosphate (PI3P), the autophagosome marker LC3, and the kinesin KIF5. Mutations in this gene are associated with inclusion body myositis (IBM) and autosomal recessive congenital cataracts (CATC2). [provided by RefSeq, Aug 2020]

MANE transcript

NM_024513.4

Inheritance

AR, AD

ClinVar variants

P:48U:283B:116

Top phenotype

Cataract 18

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr3:45,917,903-45,995,824

External References & Databases

Ensembl (ENSG00000163820)

Transcript & Mutation Effects

hg38 • Region Span ~77.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cataract 18DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012395

Submitter: G2P

cataract 18STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012395

Submitter: Labcorp Genetics (formerly Invitae)

cataract 18STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012395

Submitter: PanelApp Australia

early-onset nuclear cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020376

Submitter: Orphanet

total early-onset cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0021548

Submitter: Orphanet

Clinical Genomic Database (CGD)

Cataract 18AR

Manifestation: Ophthalmologic

Intervention: General

Rationale: 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

Refs: 11519376; 21636066

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FYCO1 variants in ClinVar

11 Conditions Cataloged

Inborn genetic diseasesTotal: 225

Cataract 18Total: 221

not providedTotal: 85

not specifiedTotal: 58

FYCO1-related disorderTotal: 40

FYCO1-related disordersTotal: 6

Susceptibility to severe COVID-19Total: 2

Bilateral congenital or childhood onset cataractsTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024513.4. 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			8 clinvar	56 clinvar	4 clinvar	68
missense		3 clinvar	269 clinvar	42 clinvar	14 clinvar	328
nonsense	14 clinvar	7 clinvar	1 clinvar			22
start loss						0
frameshift	11 clinvar	8 clinvar				19
splice donor/acceptor (+/-2bp)	1 clinvar	4 clinvar	5 clinvar			10
Total	26	22	283	98	18	447

Highest pathogenic variant AF is 0.00018835333

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_024513.4	RefSeq	NP_078789.2	17	MANE Select
ENST00000296137.7	Ensembl	ENSP00000296137.2	17	MANE Select
NM_001386421.1	RefSeq	NP_001373350.1	17	Standard
NM_001386422.1	RefSeq	NP_001373351.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

plus-end-directed vesicle transport along microtubule
positive regulation of autophagosome maturation

Molecular Function

protein binding
metal ion binding

Cellular Component

lysosome
late endosome
autophagosome
Golgi apparatus
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296137
Coding exons: 17
Length: 77921
Individuals with no LoFs: 125563
Homozygous LoFs: 1
Heterozygous LoFs: 184
Defined: 125748
p: 0.000736

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.174	764	778	0.982	0.0000476	9657
Missense (PolyPhen)		227	232.17	0.97772		3099
Synonymous	0.723	319	336	0.950	0.0000203	2871
Loss of Function	2.18	52	71.9	0.723	0.00000383	804

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00086	0.00086	rare
Latino/Admixed American	0.00052	0.00052	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00082	0.00082	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00095	0.00095	rare
South Asian	0.00052	0.00052	rare
Other	0.0011	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May mediate microtubule plus end-directed vesicle transport. {ECO:0000269|PubMed:20100911}.;

Recessive Scores

pRec: 0.0949

Intolerance Scores

LoFtool: 0.913
RVIS EVS: 3.05
RVIS percentile EVS: 99.24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.643

Gene Damage Prediction

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