FYCO1

Summary

FYCO1 (FYVE and coiled-coil domain autophagy adaptor 1, HGNC:14673) is a protein-coding gene on chromosome 3p21.31, encoding FYVE and coiled-coil domain-containing protein 1 (Q9BQS8). May mediate microtubule plus end-directed vesicle transport.

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).

Source: NCBI Gene 79443 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cataract 18 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 592 total — 29 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 4
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_024513

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14673
Approved symbol	FYCO1
Name	FYVE and coiled-coil domain autophagy adaptor 1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13335, ZFYVE7
Ensembl gene	ENSG00000163820
Ensembl biotype	protein_coding
OMIM	607182
Entrez	79443

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000296137, ENST00000433878, ENST00000438446, ENST00000471739, ENST00000691721, ENST00000874259, ENST00000965269, ENST00000965270, ENST00000965271

RefSeq mRNA: 11 — MANE Select: NM_024513 NM_001386421, NM_001386422, NM_001386423, NM_001386424, NM_001386425, NM_001386426, NM_001386427, NM_001386428, NM_001386429, NM_001386430, NM_024513

CCDS: CCDS2734

Canonical transcript exons

ENST00000296137 — 18 exons

Exon	Start	End
ENSE00001078603	45962225	45962392
ENSE00001078604	45923656	45923765
ENSE00001078605	45931071	45931281
ENSE00001078607	45966277	45968703
ENSE00001078609	45964336	45964454
ENSE00001078611	45979705	45979830
ENSE00001078617	45917903	45921840
ENSE00001078619	45981570	45981676
ENSE00001209401	45975239	45975345
ENSE00001209459	45973088	45973231
ENSE00001209468	45958408	45958619
ENSE00001213249	45959393	45959542
ENSE00001213267	45965033	45965125
ENSE00001213318	45969675	45969765
ENSE00001407614	45984856	45985022
ENSE00001934456	45995722	45995824
ENSE00003489580	45936448	45936543
ENSE00003657913	45955249	45955393

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.1271 / max 279.8591, expressed in 1810 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41920	22.6561	1810
41919	0.3316	174
41917	0.1349	31
41916	0.0045	3

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.90	gold quality
biceps brachii	UBERON:0001507	98.68	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.60	gold quality
vastus lateralis	UBERON:0001379	98.34	gold quality
quadriceps femoris	UBERON:0001377	98.10	gold quality
skeletal muscle tissue	UBERON:0001134	97.91	gold quality
body of tongue	UBERON:0011876	97.85	gold quality
triceps brachii	UBERON:0001509	97.65	gold quality
gluteal muscle	UBERON:0002000	97.51	gold quality
deltoid	UBERON:0001476	97.12	gold quality
saphenous vein	UBERON:0007318	96.79	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.65	gold quality
muscle organ	UBERON:0001630	96.39	gold quality
skeletal muscle organ	UBERON:0014892	96.39	gold quality
diaphragm	UBERON:0001103	96.34	gold quality
muscle tissue	UBERON:0002385	96.09	gold quality
gastrocnemius	UBERON:0001388	95.86	gold quality
muscle of leg	UBERON:0001383	95.76	gold quality
tibialis anterior	UBERON:0001385	95.13	gold quality
heart right ventricle	UBERON:0002080	94.84	gold quality
blood vessel layer	UBERON:0004797	94.57	gold quality
right coronary artery	UBERON:0001625	94.42	gold quality
tongue	UBERON:0001723	94.36	gold quality
left ventricle myocardium	UBERON:0006566	93.96	gold quality
popliteal artery	UBERON:0002250	93.30	gold quality
tibial artery	UBERON:0007610	93.30	gold quality
apex of heart	UBERON:0002098	93.12	gold quality
cardiac ventricle	UBERON:0002082	93.03	gold quality
artery	UBERON:0001637	92.97	gold quality
heart left ventricle	UBERON:0002084	92.95	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

224 targeting FYCO1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-12133	99.92	71.82	2006

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 15)

• Maps to a region of chromosome 3p21.3 which is frequently deleted in tumors. (PMID:11896456)
• We have characterized the LC3-, Rab7-, and phosphatidylinositol-3-phosphate-binding domains in FYCO1 and mapped part of the CC region essential for MT plus end-directed transport. (PMID:20100911)
• FYCO1 is involved in lens development and transparency in humans, and mutations in this gene are one of the most common causes of autosomal-recessive congenital cataracts in the Pakistani population. (PMID:21636066)
• FYCO1 requires a functional LC3A/B-preferring LC3-interacting Region (LIR) motif to facilitate efficient maturation of autophagosomes under basal conditions, whereas starvation-induced autophagy was unaffected (PMID:26468287)
• FYCO1 and MAP1LC3A interact through a novel binding mode that involves Atg8-family proteins (PMID:27246247)
• Rare missense variants in FYCO1 are overrepresented in sporadic inclusion body myositis patients. (PMID:28009083)
• FYCO1 regulates accumulation of post-mitotic midbodies by mediating LC3-dependent midbody degradation (PMID:29196475)
• Crystal structure of the FYCO1 RUN domain suggests possible interfaces with small GTPases. (PMID:32744243)
• Lung expression of genes putatively involved in SARS-CoV-2 infection is modulated in cis by germline variants. (PMID:33649539)
• Autosomal recessive cataract (CTRCT18) in the Yakut population isolate of Eastern Siberia: a novel founder variant in the FYCO1 gene. (PMID:33767456)
• Nlp promotes autophagy through facilitating the interaction of Rab7 and FYCO1. (PMID:33859171)
• Identification of a novel nonsense variant in FYCO1 gene associated with infantile cataract and cortical atrophy. (PMID:34282983)
• Targeted gene sequencing of FYCO1 identified a novel mutation in a Pakistani family for autosomal recessive congenital cataract. (PMID:35638468)
• A Novel Mutation in the FYCO1 Gene Causing Congenital Cataract: Case Study of a Chinese Family. (PMID:36061348)
• FYCO1 regulates migration, invasion, and invadopodia formation in HeLa cells through CDC42/N-WASP/Arp2/3 signaling pathway. (PMID:36342046)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fyco1b	ENSDARG00000078022
danio_rerio	fyco1a	ENSDARG00000104500
mus_musculus	Fyco1	ENSMUSG00000025241
rattus_norvegicus	Fyco1	ENSRNOG00000006336

Paralogs (1): RUFY4 (ENSG00000188282)

Protein

Protein identifiers

FYVE and coiled-coil domain-containing protein 1 — Q9BQS8 (reviewed: Q9BQS8)

Alternative names: Zinc finger FYVE domain-containing protein 7

All UniProt accessions (3): C9J2W6, Q9BQS8, H7BZ74

UniProt curated annotations — full annotation on UniProt →

Function. May mediate microtubule plus end-directed vesicle transport.

Subunit / interactions. Can form homodimers. Interacts (via C-terminus) with MAP1LC3B. Interacts with RAB7A; the interaction with RAB7A induces FYCO1 recruitment to late endosomal/lysosomal compartments. Interacts with MAP1LC3B.

Subcellular location. Cytoplasmic vesicle. Autophagosome. Endosome. Lysosome.

Tissue specificity. Expressed in heart and skeletal muscle.

Disease relevance. Cataract 18 (CTRCT18) [MIM:610019] An opacification of the crystalline lens of the eye becoming evident at birth or in infancy. It frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. The disease is caused by variants affecting the gene represented in this entry. Pathogenic mutations in FYCO1 can affect intracellular transport of autophagocytic vesicles from the perinuclear area to the periphery, leading to an accumulation of large numbers of vesicles and hence loss of lens transparency.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BQS8-1	1	yes
Q9BQS8-2	2
Q9BQS8-3	3
Q9BQS8-4	4

RefSeq proteins (11): NP_001373350, NP_001373351, NP_001373352, NP_001373353, NP_001373354, NP_001373355, NP_001373356, NP_001373357, NP_001373358, NP_001373359, NP_078789* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000306	Znf_FYVE	Domain
IPR004012	Run_dom	Domain
IPR009038	GOLD_dom	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017455	Znf_FYVE-rel	Domain
IPR036598	GOLD_dom_sf	Homologous_superfamily
IPR037213	Run_dom_sf	Homologous_superfamily
IPR047336	RUN_FYCO1	Domain
IPR047337	FYVE_FYCO1	Domain

Pfam: PF01363, PF02759

UniProt features (64 total): sequence variant 10, helix 10, binding site 8, sequence conflict 8, modified residue 5, coiled-coil region 4, splice variant 4, compositionally biased region 3, region of interest 3, strand 3, domain 2, initiator methionine 1, chain 1, zinc finger region 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7BQI	X-RAY DIFFRACTION	1.3
5D94	X-RAY DIFFRACTION	1.53
5CX3	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQS8-F1	72.64	0.15

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 1179; 1182; 1195; 1198; 1203; 1206; 1223; 1226

Post-translational modifications (5): 2, 196, 342, 381, 878

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 222 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOBP_VESICLE_LOCALIZATION, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GGAMTNNNNNTCCY_UNKNOWN, GOBP_MACROAUTOPHAGY, GOBP_VESICLE_CYTOSKELETAL_TRAFFICKING, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, BLALOCK_ALZHEIMERS_DISEASE_UP, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, AACTTT_UNKNOWN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (2): plus-end-directed vesicle transport along microtubule (GO:0072383), positive regulation of autophagosome maturation (GO:1901098)

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): lysosome (GO:0005764), late endosome (GO:0005770), autophagosome (GO:0005776), Golgi apparatus (GO:0005794), membrane (GO:0016020), endosome (GO:0005768), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
endomembrane system	2
vesicle transport along microtubule	1
plus-end-directed organelle transport along microtubule	1
positive regulation of organelle organization	1
positive regulation of macroautophagy	1
positive regulation of protein-containing complex disassembly	1
autophagosome maturation	1
regulation of autophagosome maturation	1
transition metal ion binding	1
binding	1
cation binding	1
lytic vacuole	1
endosome	1
vacuole	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
cytoplasmic vesicle	1
intracellular vesicle	1

Protein interactions and networks

STRING

1378 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FYCO1	CXCR6	O00574	930
FYCO1	MAP1LC3B	Q9GZQ8	930
FYCO1	ZFYVE27	Q5T4F4	880
FYCO1	RAB40AL	P0C0E4	857
FYCO1	LZTFL1	Q9NQ48	805
FYCO1	SLC6A20	Q9NP91	785
FYCO1	GABARAPL2	P60520	780
FYCO1	F5GZY7	F5GZY7	780
FYCO1	MAP1LC3A	Q9H492	750
FYCO1	PLEKHM1	Q9Y4G2	732
FYCO1	RAB7A	P51149	655
FYCO1	XCR1	P46094	650
FYCO1	CRYBB1	P53674	646
FYCO1	CRYAA	P02489	643
FYCO1	CCR9	P51686	638

IntAct

99 interactions, top by confidence:

A	B	Type	Score
DTNB	DMD	psi-mi:“MI:0914”(association)	0.890
HIF1AN	APBA3	psi-mi:“MI:0914”(association)	0.850
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
MAP1LC3B	FYCO1	psi-mi:“MI:0407”(direct interaction)	0.760
FYCO1	MAP1LC3B	psi-mi:“MI:0915”(physical association)	0.760
MAP1LC3B	MAP1B	psi-mi:“MI:0914”(association)	0.730
KLHDC2	CUL2	psi-mi:“MI:0914”(association)	0.730
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
MAP1LC3B	OFD1	psi-mi:“MI:0914”(association)	0.660
FYCO1	rep	psi-mi:“MI:0915”(physical association)	0.660
FYCO1	KIF5B	psi-mi:“MI:0915”(physical association)	0.640
HIF1AN	GMDS	psi-mi:“MI:0914”(association)	0.640
CCDC68	NDC80	psi-mi:“MI:0914”(association)	0.640
RCCD1	SPAG9	psi-mi:“MI:0914”(association)	0.640
FYCO1	KLC2	psi-mi:“MI:0407”(direct interaction)	0.540
FYCO1	KLC2	psi-mi:“MI:0915”(physical association)	0.540
GABARAP	FYCO1	psi-mi:“MI:0407”(direct interaction)	0.540
GABARAPL1	FYCO1	psi-mi:“MI:0407”(direct interaction)	0.540
GABARAPL2	FYCO1	psi-mi:“MI:0407”(direct interaction)	0.540
FYCO1	MAP1LC3C	psi-mi:“MI:0407”(direct interaction)	0.540
FYCO1	GABARAPL1	psi-mi:“MI:0915”(physical association)	0.540
GABARAPL2	FYCO1	psi-mi:“MI:0915”(physical association)	0.540
GABARAP	FYCO1	psi-mi:“MI:0915”(physical association)	0.540
FYCO1	MAP1LC3C	psi-mi:“MI:0915”(physical association)	0.540
BORCS6	HSBP1	psi-mi:“MI:0914”(association)	0.530
TRUB2	HSPD1	psi-mi:“MI:0914”(association)	0.530

BioGRID (160): FYCO1 (Two-hybrid), FYCO1 (Affinity Capture-RNA), CCT7 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), DTNA (Affinity Capture-MS), TCP1 (Affinity Capture-MS), MLYCD (Affinity Capture-MS), SASS6 (Affinity Capture-MS), FYCO1 (Affinity Capture-MS), FYCO1 (Affinity Capture-MS), FYCO1 (Affinity Capture-MS), FYCO1 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LIT1, A0A1B0GVG4, A0JNH6, A1A5D9, A6NC98, A6NGB0, A6NJZ7, A6NNM3, F6XLV1, O15049, O54887, P0C7N4, P58660, P60531, Q0D2H9, Q0P5D1, Q2KJ21, Q2TAC2, Q3LUD3, Q3T1I3, Q3TMW1, Q3V0F0, Q4QRL3, Q5JTB6, Q5RD60, Q66HR5, Q6NSJ2, Q6PHN1, Q6QZQ4, Q80VM7, Q8BP01, Q8C7U1, Q8CB62, Q8CGU1, Q8CHW5, Q8K2I2, Q8N137, Q8N283, Q8N6Y0, Q8R370

Diamond homologs: A0A0D1E015, A0JMD2, A1CEK1, A1DFP5, A2QWA2, A4QTV1, A8QCE4, A8XJZ8, B0G126, B0WAQ0, B3MT31, B3P851, B4G2G5, B4IC49, B4JHI7, B4K982, B4M140, B4NFJ7, B4PRU6, D2H5P6, D3ZVP7, D4A8G9, E1BLZ4, F1MM41, F7EP40, O13821, O14964, O59722, O76902, O95405, O96838, P0CS26, P0CS27, P34756, P40343, Q05B78, Q08CN9, Q0CJV3, Q0P4S0, Q0U4Z8

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
FYCO1	“up-regulates activity”	MAP1LC3B	binding
FYCO1	“up-regulates activity”	MAP1LC3A	binding
KLC2	“up-regulates activity”	FYCO1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Macroautophagy	7	12.2×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	10	36.5×	4e-11
lysosome localization	5	30.3×	8e-05
autophagosome maturation	7	28.2×	8e-07
autophagosome assembly	9	23.2×	3e-08
protein transport	11	5.5×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

592 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	29
Likely pathogenic	9
Uncertain significance	321
Likely benign	79
Benign	98

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1193629	NM_024513.4(FYCO1):c.3307C>T (p.Gln1103Ter)	Pathogenic
1322945	NM_024513.4(FYCO1):c.524G>A (p.Trp175Ter)	Pathogenic
1386641	NM_024513.4(FYCO1):c.3861del (p.Glu1287fs)	Pathogenic
1430203	NM_024513.4(FYCO1):c.528_529insGGCAAAGT (p.Thr177fs)	Pathogenic
1443310	NM_024513.4(FYCO1):c.575G>A (p.Trp192Ter)	Pathogenic
1447466	NM_024513.4(FYCO1):c.3161del (p.Ala1054fs)	Pathogenic
1457244	NM_024513.4(FYCO1):c.3322A>T (p.Lys1108Ter)	Pathogenic
1709262	NM_024513.4(FYCO1):c.265_267delinsTGA (p.Arg89Ter)	Pathogenic
2203348	NM_024513.4(FYCO1):c.2345del (p.Gln782fs)	Pathogenic
2636094	NM_024513.4(FYCO1):c.3670C>T (p.Arg1224Ter)	Pathogenic
3029278	NM_024513.4(FYCO1):c.4270C>T (p.Arg1424Ter)	Pathogenic
3046836	NM_024513.4(FYCO1):c.3270-2A>C	Pathogenic
30645	NM_024513.4(FYCO1):c.1045C>T (p.Gln349Ter)	Pathogenic
30646	NM_024513.4(FYCO1):c.2206C>T (p.Gln736Ter)	Pathogenic
30648	NM_024513.4(FYCO1):c.3858_3862dup (p.Leu1288fs)	Pathogenic
30649	NM_024513.4(FYCO1):c.4127T>C (p.Leu1376Pro)	Pathogenic
30650	NM_024513.4(FYCO1):c.1546C>T (p.Gln516Ter)	Pathogenic
3257352	NM_024513.4(FYCO1):c.2710_2713del (p.Asp904fs)	Pathogenic
3359081	NM_024513.4(FYCO1):c.2386C>T (p.Gln796Ter)	Pathogenic
3665660	NM_024513.4(FYCO1):c.2483_2487dup (p.Leu830fs)	Pathogenic
3694827	NM_024513.4(FYCO1):c.1410G>A (p.Trp470Ter)	Pathogenic
3726918	NM_024513.4(FYCO1):c.2308del (p.Gln770fs)	Pathogenic
3778776	NM_024513.4(FYCO1):c.402G>A (p.Trp134Ter)	Pathogenic
4293908	NM_024513.4(FYCO1):c.3412G>T (p.Glu1138Ter)	Pathogenic
430962	NM_024513.4(FYCO1):c.3327_3328del (p.Cys1110fs)	Pathogenic
4747891	NM_024513.4(FYCO1):c.1327del (p.Ala443fs)	Pathogenic
660217	NM_024513.4(FYCO1):c.2505del (p.Ala836fs)	Pathogenic
817447	NM_024513.4(FYCO1):c.830_833del (p.Glu277fs)	Pathogenic
982778	NM_024513.4(FYCO1):c.1411C>T (p.Arg471Ter)	Pathogenic
2500891	NM_024513.4(FYCO1):c.3456G>A (p.Trp1152Ter)	Likely pathogenic

SpliceAI

2920 predictions. Top by Δscore:

Variant	Effect	Δscore
3:45921729:T:A	donor_gain	1.0000
3:45923650:CCCTA:C	donor_loss	1.0000
3:45923651:CCTAC:C	donor_loss	1.0000
3:45923652:CTAC:C	donor_loss	1.0000
3:45923653:TACCT:T	donor_loss	1.0000
3:45923655:CCTTG:C	donor_loss	1.0000
3:45931066:CTTA:C	donor_loss	1.0000
3:45931069:A:AG	donor_loss	1.0000
3:45931070:C:CG	donor_loss	1.0000
3:45931070:CCTTA:C	donor_gain	1.0000
3:45936443:CTTA:C	donor_loss	1.0000
3:45936444:TTAC:T	donor_loss	1.0000
3:45936446:A:AC	donor_gain	1.0000
3:45936446:ACAT:A	donor_gain	1.0000
3:45936447:C:CA	donor_gain	1.0000
3:45936447:CA:C	donor_gain	1.0000
3:45936447:CAT:C	donor_gain	1.0000
3:45936447:CATC:C	donor_gain	1.0000
3:45936447:CATCA:C	donor_gain	1.0000
3:45936541:TCC:T	acceptor_gain	1.0000
3:45936542:CCC:C	acceptor_gain	1.0000
3:45936544:C:CC	acceptor_gain	1.0000
3:45936549:A:AC	acceptor_gain	1.0000
3:45955247:A:AC	donor_gain	1.0000
3:45955248:C:CC	donor_gain	1.0000
3:45955248:CTGTT:C	donor_gain	1.0000
3:45955413:C:CT	acceptor_gain	1.0000
3:45955414:A:T	acceptor_gain	1.0000
3:45959427:C:CA	donor_gain	1.0000
3:45959555:C:T	acceptor_gain	1.0000

AlphaMissense

9712 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:45962231:A:G	L1144P	0.999
3:45973104:A:G	W175R	0.999
3:45973104:A:T	W175R	0.999
3:45975319:T:A	R105S	0.999
3:45975319:T:G	R105S	0.999
3:45931154:A:G	W1390R	0.998
3:45931154:A:T	W1390R	0.998
3:45962240:A:G	L1141P	0.998
3:45973102:C:A	W175C	0.998
3:45973102:C:G	W175C	0.998
3:45973210:G:C	S139R	0.998
3:45973210:G:T	S139R	0.998
3:45973212:T:G	S139R	0.998
3:45975264:A:G	C124R	0.998
3:45975320:C:G	R105T	0.998
3:45975330:C:A	G102W	0.998
3:45979721:A:T	V91D	0.998
3:45981574:A:G	L53P	0.998
3:45981577:A:G	L52P	0.998
3:45981586:A:G	L49P	0.998
3:45921829:T:A	K1458I	0.997
3:45973142:A:G	F162S	0.997
3:45975308:C:G	R109P	0.997
3:45975314:A:G	F107S	0.997
3:45975324:C:G	G104R	0.997
3:45975324:C:T	G104R	0.997
3:45975330:C:G	G102R	0.997
3:45975330:C:T	G102R	0.997
3:45979782:A:G	W71R	0.997
3:45979782:A:T	W71R	0.997

dbSNP variants (sampled 300 via entrez): RS1000078666 (3:45926182 G>A,T), RS1000226972 (3:45958072 C>G), RS1000232177 (3:45930636 TG>T), RS1000251030 (3:45977781 T>C), RS1000264484 (3:45932397 C>T), RS1000312332 (3:45920050 G>A), RS1000321970 (3:45983845 C>T), RS1000394787 (3:45991988 G>A), RS1000397354 (3:45969061 G>T), RS1000469340 (3:45952735 G>C), RS1000513400 (3:45970576 C>G,T), RS1000535590 (3:45956492 G>A), RS1000569659 (3:45949892 A>C), RS1000699959 (3:45932184 G>A), RS1000782074 (3:45956816 T>C)

Disease associations

OMIM: gene MIM:607182 | disease phenotypes: MIM:610019

GenCC curated gene-disease

Disease	Classification	Inheritance
cataract 18	Definitive	Autosomal recessive
early-onset nuclear cataract	Supportive	Autosomal dominant
total early-onset cataract	Supportive	Autosomal dominant

Mondo (3): cataract 18 (MONDO:0012395), early-onset nuclear cataract (MONDO:0020376), total early-onset cataract (MONDO:0021548)

Orphanet (4): Early onset non-syndromic cataract (Orphanet:91492), Early-onset nuclear cataract (Orphanet:98991), Early-onset partial cataract (Orphanet:98992), Early-onset zonular cataract (Orphanet:98995)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0100018	Nuclear cataract

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009378_6	Bone mineral content	4.000000e-06
GCST90000255_22	Severe COVID-19 infection with respiratory failure (analysis I)	1.000000e-10
GCST90000256_1	Severe COVID-19 infection with respiratory failure (analysis II)	9.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007621	bone mineral content measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C563333	Cataract, Age-Related Nuclear (supp.)
C535337	Cataract, autosomal recessive congenital 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	affects cotreatment, increases methylation, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	increases expression	1
perfluorooctanoic acid	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression, affects cotreatment	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
licochalcone B	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	increases abundance, affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Benztropine	decreases expression, affects cotreatment	1
Cannabidiol	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Coumestrol	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT06068348	Not specified	ACTIVE_NOT_RECRUITING	Liquid Biopsy Collection Study