UBIAD1

Summary

UBIAD1 (UbiA prenyltransferase domain containing 1, HGNC:30791) is a protein-coding gene on chromosome 1p36.22, encoding UbiA prenyltransferase domain-containing protein 1 (Q9Y5Z9). Prenyltransferase that mediates the formation of menaquinone-4 (MK-4) and coenzyme Q10. It is a selective cancer dependency (DepMap: 37.6% of cell lines).

This gene encodes a protein thought to be involved in cholesterol and phospholipid metabolism. Mutations in this gene are associated with Schnyder crystalline corneal dystrophy.

Source: NCBI Gene 29914 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Schnyder corneal dystrophy (Definitive, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 134 total — 10 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 3
• Cancer dependency (DepMap): dependent in 37.6% of screened cell lines
• MANE Select transcript: NM_013319

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30791
Approved symbol	UBIAD1
Name	UbiA prenyltransferase domain containing 1
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	TERE1
Ensembl gene	ENSG00000120942
Ensembl biotype	protein_coding
OMIM	611632
Entrez	29914

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000376804, ENST00000376810, ENST00000483738, ENST00000486588

RefSeq mRNA: 3 — MANE Select: NM_013319 NM_001330349, NM_001330350, NM_013319

CCDS: CCDS129, CCDS81260

Canonical transcript exons

ENST00000376810 — 2 exons

Exon	Start	End
ENSE00001471741	11285644	11288434
ENSE00001550950	11273198	11274060

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 85.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5400 / max 89.3846, expressed in 1797 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
615	8.0687	1755
617	5.8637	1531
616	1.6075	1104

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	85.46	gold quality
muscle of leg	UBERON:0001383	84.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.15	gold quality
secondary oocyte	CL:0000655	83.72	gold quality
upper leg skin	UBERON:0004262	83.44	gold quality
oocyte	CL:0000023	83.00	gold quality
muscle organ	UBERON:0001630	82.12	gold quality
ganglionic eminence	UBERON:0004023	82.06	gold quality
islet of Langerhans	UBERON:0000006	81.08	gold quality
nipple	UBERON:0002030	81.03	gold quality
granulocyte	CL:0000094	80.95	gold quality
cortical plate	UBERON:0005343	80.83	gold quality
ventricular zone	UBERON:0003053	80.62	gold quality
endothelial cell	CL:0000115	80.57	gold quality
mammalian vulva	UBERON:0000997	80.49	gold quality
deltoid	UBERON:0001476	80.36	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	79.59	gold quality
pigmented layer of retina	UBERON:0001782	79.18	gold quality
popliteal artery	UBERON:0002250	79.16	gold quality
tibial artery	UBERON:0007610	79.15	gold quality
lymph node	UBERON:0000029	79.14	gold quality
pancreas	UBERON:0001264	78.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.98	gold quality
spinal cord	UBERON:0002240	78.94	gold quality
body of pancreas	UBERON:0001150	78.83	gold quality
right ovary	UBERON:0002118	78.72	gold quality
left adrenal gland	UBERON:0001234	78.67	gold quality
stromal cell of endometrium	CL:0002255	78.66	gold quality
left ovary	UBERON:0002119	78.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2, YY1

miRNA regulators (miRDB)

101 targeting UBIAD1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 37.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 36)

• TERE1 maybe significant in prostate cancer growth regulation and the down regulation or absence of TERE1 may be an important component of the phenotype of advanced disease (PMID:12497587)
• The objective of this study was to gain further insight into the function of the TERE1 protein by identifying potential protein to protein interactions with TERE1 (PMID:15782423)
• Data suggest that UBIAD1 encodes a potential prenyltransferase, and may play a direct role in intracellular cholesterol biochemistry, or may prenylate other proteins regulating cholesterol transport and storage. (PMID:17668063)
• Missense mutations in UBIAD1, located just outside of originally described Schnyder crystalline corneal dystrophy(SCCD) fine mapped region, were identified in each of three families with SCCD, confirming that mutations in UBIAD1 are associated with SCCD. (PMID:17960116)
• Nonsynonymous mutations in the UBIAD1 gene were detected in six SCCD (Schnyder crystalline corneal dystrophy) families, and a potential mutation hot spot was observed at amino acid N102. (PMID:17962451)
• Schnyder crystalline corneal dystrophy mutations affect function, ligand binding and interaction with binding partners, like apolipoproteins E. (PMID:18176953)
• Nonsynonymous novel mutations in the UBIAD1 gene were detected in 3 unrelated Japanese pedigrees with Schnyder’s crystalline corneal dystrophy (SCCD), confirming the genetic heterogeneity of this disorder. (PMID:19394700)
• Screening of the UBIAD1 gene identified a highly conserved mutation, Ser171Pro in a chinese family. (PMID:19429578)
• The newly identified mutation expands the spectrum of mutations in UBIAD1 that may cause pathological corneal cholesterol deposition. (PMID:19649163)
• Our newly reported UBIAD1 mutation suggests that central discoid corneal dystrophy (CDCD) is actually a variant of schnyder corneal dystrophy. (PMID:20489584)
• Mitochondrial UBIAD1 protein appears to have a highly conserved function that, at least in humans, is involved in cholesterol metabolism in a novel manner. (PMID:20505825)
• UBIAD1 encodes a menaquinone-4 biosynthetic enzyme that converts phylloquinone (PK) to menaquinone-4 (MK-4) (PMID:20953171)
• results show that UBIAD1 is a human MK-4 biosynthetic enzyme; this identification will permit more effective decisions to be made about vitamin K intake and bone health (PMID:20953171)
• the inhibitory effects of ectopic TERE1 expression on tumorigenic growth (PMID:21740188)
• The nonsynonymous mutation, N102S, in the UBIAD1 gene has been detected in in a four-generation Chinese family with Schnyder corneal dystrophy (SCD). (PMID:22065921)
• Physical association of UBIAD1 with enzymes involved in cholesterol synthesis and storage, providing direct links between UBIAD1 and cholesterol metabolism that are likely relevant to Schnyder corneal dystrophy disease pathology. (PMID:23169578)
• Findings identify UBIAD1 as a nonmitochondrial CoQ10-forming enzyme with specific cardiovascular protective function via the modulation of eNOS activity. (PMID:23374346)
• UBIAD1-mediated vitamin K2 synthesis is required for vascular endothelial cell survival and development. (PMID:23533172)
• A TERE1-TBL2 complex likely functions in oxidative/nitrosative stress, lipid metabolism, and SXR signaling pathways in its role as a tumor suppressor. (PMID:23564352)
• Loss of TERE1 may contribute to the altered lipid metabolic phenotype associated with progression in renal clear cell carcinoma via an uncoupling of reactive oxygen species/nitric oxide and SXR signaling from apoptosis by elevation of cholesterol. (PMID:23759948)
• Golgi localization of UBIAD1 influences its tumor suppressant activity. (PMID:23977195)
• N102S may also be a mutation hotspot in the Polish population, as in other previously reported populations. (PMID:24608252)
• Data show that sterols stimulate binding of prenyltransferase UBIAD1 to HMG CoA reductase, which is subject to sterol-accelerated, endoplasmic reticulum (ER)-associated degradation augmented by the nonsterol isoprenoid geranylgeraniol. (PMID:25742604)
• results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter (PMID:25772619)
• The conserved domain I is a substrate recognition site that undergoes a structural change after substrate binding. (PMID:25874989)
• UBIAD1 or menaquinone-4 could decrease vascular cell differentiation and calcification, probably via its potent role of inversely modulating cellular cholesterol. (PMID:26890002)
• these findings disclose a novel sensing mechanism that allows for stringent metabolic control of intracellular trafficking of UBIAD1, which directly modulates reductase degradation and becomes disrupted in Schnyder corneal dystrophy (SCD). (PMID:27121042)
• Silencing UBIAD1 further aggravates the deleterious effects rendered by Ang II, indicating that a normal or increased level of UBIAD1 may offer protection against the Ang IIinduced hypertrophic response and apoptosis. (PMID:28901410)
• The novel p.Thr120Arg is the fourth Schnyder corneal dystrophy-causing variant lying within the FARM motif of the UBIAD1 protein, which underlines a high importance of this motif for SCD pathogenesis. (PMID:30084067)
• Although de novo occurrence of mutations in UBIAD1 is extremely rare, SCD should be considered in the differential diagnosis of bilateral corneal haze and/or crystal deposition, especially in children (PMID:30223810)
• Genetic analysis of our family revealed a mutation of the UBIAD1 gene not described in the literature for Schnyder Dystrophy. (PMID:30446344)
• UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras. (PMID:30518913)
• Results demonstrate that schnyder corneal dystrophy (SCD)-associated mutations of UBIAD1 impair its ER-to-Golgi transportation and enhance its interaction with HMGCR. The stabilization of HMGCR by UBIAD1 increases cholesterol biosynthesis and eventually causes cholesterol accumulation in the cornea. (PMID:31323021)
• Schnyder corneal dystrophy-associated UBIAD1 is defective in MK-4 synthesis and resists autophagy-mediated degradation. (PMID:32188638)
• Functional study of SCCD pathogenic gene UBIAD1 (Review). (PMID:34368857)
• UBIAD1 and CoQ10 protect melanoma cells from lipid peroxidation-mediated cell death. (PMID:35255427)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubiad1	ENSDARG00000013009
mus_musculus	Ubiad1	ENSMUSG00000047719
rattus_norvegicus	Ubiad1	ENSRNOG00000009575
drosophila_melanogaster	heix	FBGN0028375

Protein

Protein identifiers

UbiA prenyltransferase domain-containing protein 1 — Q9Y5Z9 (reviewed: Q9Y5Z9)

Alternative names: Transitional epithelial response protein 1

All UniProt accessions (3): Q9Y5Z9, R4GN21, R4GNE3

UniProt curated annotations — full annotation on UniProt →

Function. Prenyltransferase that mediates the formation of menaquinone-4 (MK-4) and coenzyme Q10. MK-4 is a vitamin K2 isoform present at high concentrations in the brain, kidney and pancreas, and is required for endothelial cell development. Mediates the conversion of phylloquinone (PK) into MK-4, probably by cleaving the side chain of phylloquinone (PK) to release 2-methyl-1,4-naphthoquinone (menadione; K3) and then prenylating it with geranylgeranyl pyrophosphate (GGPP) to form MK-4. Also plays a role in cardiovascular development independently of MK-4 biosynthesis, by acting as a coenzyme Q10 biosynthetic enzyme: coenzyme Q10, also named ubiquinone, plays an important antioxidant role in the cardiovascular system. Mediates biosynthesis of coenzyme Q10 in the Golgi membrane, leading to protect cardiovascular tissues from NOS3/eNOS-dependent oxidative stress.

Subunit / interactions. Interacts with HMGCR and SOAT1.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane. Mitochondrion membrane. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitously expressed.

Disease relevance. Corneal dystrophy, Schnyder type (SCCD) [MIM:121800] A form of stromal corneal dystrophy characterized by corneal clouding, resulting from abnormal deposition of cholesterol and phospholipids, and decreased visual acuity. Typically, ring-shaped yellow-white opacities composed of innumerable fine needle-shaped crystals form in Bowman layer and the adjacent anterior stroma of the central cornea. The crystals usually remain in the anterior third of the cornea. The corneal epithelium and endothelium as well as Descemet membrane are spared. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Quinol/quinone metabolism; menaquinone biosynthesis. Cofactor biosynthesis; ubiquinone biosynthesis.

Miscellaneous. Strongly down-regulated in transitional cell carcinoma of the bladder and in prostate carcinoma (at protein level).

Similarity. Belongs to the UbiA prenyltransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y5Z9-1	1	yes
Q9Y5Z9-2	2

RefSeq proteins (3): NP_001317278, NP_001317279, NP_037451* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000537	UbiA_prenyltransferase	Family
IPR026046	UBIAD1	Family
IPR044878	UbiA_sf	Homologous_superfamily

Pfam: PF01040

Catalyzed reactions (Rhea), 2 shown:

• all-trans-decaprenyl diphosphate + 4-hydroxybenzoate = 4-hydroxy-3-(all-trans-decaprenyl)benzoate + diphosphate (RHEA:44564)
• menadiol + (2E,6E,10E)-geranylgeranyl diphosphate = menaquinol-4 + diphosphate (RHEA:74083)

UniProt features (34 total): sequence variant 20, transmembrane region 8, splice variant 2, initiator methionine 1, chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5Z9-F1	90.21	0.83

Functional residue map

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

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6806664	Metabolism of vitamin K

MSigDB gene sets: 143 (showing top): GOBP_KETONE_METABOLIC_PROCESS, YY1_Q6, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, MYCMAX_01, GOBP_VITAMIN_BIOSYNTHETIC_PROCESS, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, GOBP_DETOXIFICATION, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_KETONE_BIOSYNTHETIC_PROCESS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOMF_ANTIOXIDANT_ACTIVITY, GOBP_RESPONSE_TO_TOXIC_SUBSTANCE, HAMAI_APOPTOSIS_VIA_TRAIL_DN

GO Biological Process (9): ubiquinone biosynthetic process (GO:0006744), menaquinone biosynthetic process (GO:0009234), vitamin K biosynthetic process (GO:0042371), vitamin K metabolic process (GO:0042373), menaquinone metabolic process (GO:0009233), ketone metabolic process (GO:0042180), obsolete phylloquinone metabolic process (GO:0042374), small molecule metabolic process (GO:0044281), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (7): prenyltransferase activity (GO:0004659), 4-hydroxybenzoate polyprenyltransferase activity (GO:0008412), antioxidant activity (GO:0016209), menadiol geranylgeranyltransferase activity (GO:0120566), protein binding (GO:0005515), transferase activity (GO:0016740), transferase activity, transferring alkyl or aryl (other than methyl) groups (GO:0016765)

GO Cellular Component (11): Golgi membrane (GO:0000139), nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), mitochondrial membrane (GO:0031966), mitochondrion (GO:0005739), Golgi apparatus (GO:0005794), endomembrane system (GO:0012505), organelle membrane (GO:0031090)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of fat-soluble vitamins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	4
cellular anatomical structure	3
cytoplasm	3
ketone biosynthetic process	2
ketone metabolic process	2
metabolic process	2
prenyltransferase activity	2
endomembrane system	2
organelle membrane	2
ubiquinone metabolic process	1
quinone biosynthetic process	1
menaquinone metabolic process	1
fat-soluble vitamin biosynthetic process	1
vitamin K metabolic process	1
cellular detoxification	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
molecular_function	1
cellular oxidant detoxification	1
binding	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
intracellular anatomical structure	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
mitochondrion	1
mitochondrial envelope	1
vacuole	1
plasma membrane	1
membrane	1
membrane-bounded organelle	1

Protein interactions and networks

STRING

1336 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBIAD1	DISP3	Q9P2K9	951
UBIAD1	FBXO2	Q9UK22	830
UBIAD1	HMGCR	P04035	734
UBIAD1	COQ2	Q96H96	680
UBIAD1	GGCX	P38435	644
UBIAD1	CHST6	Q9GZX3	636
UBIAD1	DISP1	Q96F81	598
UBIAD1	SOAT1	P35610	591
UBIAD1	KRT3	P12035	549
UBIAD1	RNF145	Q96MT1	530
UBIAD1	COX10	Q12887	518
UBIAD1	KRT12	Q99456	516
UBIAD1	TBL2	Q9Y4P3	483
UBIAD1	VKORC1	Q9BQB6	483
UBIAD1	SLC4A11	Q8NBS3	482

IntAct

165 interactions, top by confidence:

A	B	Type	Score
UBIAD1	HMGCR	psi-mi:“MI:0915”(physical association)	0.620
HMGCR	UBIAD1	psi-mi:“MI:0915”(physical association)	0.620
HMGCR	UBIAD1	psi-mi:“MI:0403”(colocalization)	0.620
UBIAD1	HRAS	psi-mi:“MI:0403”(colocalization)	0.580
UBIAD1	HRAS	psi-mi:“MI:2364”(proximity)	0.580
UBIAD1	HRAS	psi-mi:“MI:0915”(physical association)	0.580
HRAS	UBIAD1	psi-mi:“MI:0403”(colocalization)	0.580
UBIAD1	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
UBIAD1	TMEFF2	psi-mi:“MI:0915”(physical association)	0.560
UBIAD1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
UBIAD1	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
UBIAD1	NCAPH2	psi-mi:“MI:0915”(physical association)	0.560
UBIAD1	PIGP	psi-mi:“MI:0915”(physical association)	0.560
BIK	UBIAD1	psi-mi:“MI:0915”(physical association)	0.560
ASGR2	UBIAD1	psi-mi:“MI:0915”(physical association)	0.560
AHNAK2	UBIAD1	psi-mi:“MI:0915”(physical association)	0.560
CLDN7	UBIAD1	psi-mi:“MI:0915”(physical association)	0.560
SLC7A14	UBIAD1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (154): UBIAD1 (Proximity Label-MS), UBIAD1 (Proximity Label-MS), UBIAD1 (Affinity Capture-MS), UBIAD1 (Affinity Capture-MS), UBIAD1 (Affinity Capture-MS), UBIAD1 (Affinity Capture-MS), HMGCR (Two-hybrid), SOAT1 (Two-hybrid), VEGFA (Two-hybrid), HMGCR (Affinity Capture-Western), SOAT1 (Affinity Capture-Western), UBIAD1 (Affinity Capture-Western), UBIAD1 (Affinity Capture-Western), UBIAD1 (Affinity Capture-MS), UBIAD1 (Proximity Label-MS)

ESM2 similar proteins: A0A1B0GVZ9, A4IFN5, A5PK40, A6NH52, A6NI61, B2LYG4, B2RZC9, B6ID01, D2HKB0, D3ZG27, P86229, Q0VDI3, Q15012, Q15546, Q17QJ2, Q1RLT2, Q2TA01, Q4R4I5, Q4R6E8, Q5H8A4, Q5R7Q1, Q5RAH0, Q5RL79, Q5U3C3, Q5VTY9, Q5ZML7, Q64232, Q6PHN7, Q6QRN8, Q719N3, Q71SV0, Q8BWB6, Q8IY49, Q8N6M3, Q8NFT2, Q8R189, Q8VD53, Q8VDI9, Q8VDR5, Q9CQC4

Diamond homologs: D2HKB0, D3ZG27, E7FB98, P32166, P39582, Q28HR4, Q54K99, Q5ZKS8, Q9DC60, Q9V3R8, Q9Y5Z9, P65651, P9WIP2, P9WIP3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
UBIAD1	down-regulates	Proliferation
UBIAD1	“down-regulates activity”	HRAS	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 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
R-HSA-425366	5	14.9×	4e-04
SLC-mediated transmembrane transport	7	6.8×	1e-03
Neutrophil degranulation	9	3.4×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	3
Uncertain significance	89
Likely benign	4
Benign	24

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
4746755	NM_013319.3(UBIAD1):c.308C>T (p.Thr103Ile)	Pathogenic
856	NM_013319.3(UBIAD1):c.305A>G (p.Asn102Ser)	Pathogenic
857	NM_013319.3(UBIAD1):c.529G>C (p.Gly177Arg)	Pathogenic
858	NM_013319.3(UBIAD1):c.355A>G (p.Arg119Gly)	Pathogenic
859	NM_013319.3(UBIAD1):c.524C>T (p.Thr175Ile)	Pathogenic
860	NM_013319.3(UBIAD1):c.695A>G (p.Asn232Ser)	Pathogenic
861	NM_013319.3(UBIAD1):c.335A>G (p.Asp112Gly)	Pathogenic
862	NM_013319.3(UBIAD1):c.511T>C (p.Ser171Pro)	Pathogenic
863	NM_013319.3(UBIAD1):c.556G>A (p.Gly186Arg)	Pathogenic
864	NM_013319.3(UBIAD1):c.708C>G (p.Asp236Glu)	Pathogenic
1300209	NM_013319.3(UBIAD1):c.718G>A (p.Asp240Asn)	Likely pathogenic
3376980	NM_013319.3(UBIAD1):c.362T>G (p.Leu121Arg)	Likely pathogenic
41408	NM_013319.3(UBIAD1):c.530G>A (p.Gly177Glu)	Likely pathogenic

SpliceAI

445 predictions. Top by Δscore:

Variant	Effect	Δscore
1:11274057:GGAG:G	donor_gain	1.0000
1:11274058:G:GT	donor_gain	1.0000
1:11274060:GGTA:G	donor_loss	1.0000
1:11274061:G:GC	donor_loss	1.0000
1:11274062:T:G	donor_loss	1.0000
1:11278691:G:GT	donor_gain	1.0000
1:11274056:AGGAG:A	donor_gain	0.9900
1:11274057:GGAGG:G	donor_gain	0.9900
1:11274058:GAG:G	donor_gain	0.9900
1:11274061:G:GG	donor_gain	0.9900
1:11278694:G:GG	donor_gain	0.9900
1:11285635:T:TA	acceptor_gain	0.9900
1:11278767:G:GT	donor_gain	0.9800
1:11285636:G:A	acceptor_gain	0.9800
1:11278693:A:AG	donor_gain	0.9700
1:11285638:CCGCA:C	acceptor_loss	0.9700
1:11285639:CGCAG:C	acceptor_loss	0.9700
1:11285640:GCA:G	acceptor_loss	0.9700
1:11285641:CAGGA:C	acceptor_loss	0.9700
1:11285642:A:AG	acceptor_gain	0.9700
1:11285642:A:T	acceptor_loss	0.9700
1:11285643:G:GG	acceptor_gain	0.9700
1:11285643:GGA:G	acceptor_gain	0.9700
1:11273330:T:TA	donor_gain	0.9500
1:11273331:A:AA	donor_gain	0.9500
1:11285635:T:A	acceptor_loss	0.9500
1:11278771:T:G	donor_gain	0.9400
1:11282056:TTC:T	acceptor_gain	0.9300
1:11285642:AG:A	acceptor_gain	0.9100
1:11285643:GG:G	acceptor_gain	0.9100

AlphaMissense

2168 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:11273692:G:C	R54T	0.999
1:11273692:G:T	R54M	0.999
1:11273837:C:A	N102K	0.999
1:11273837:C:G	N102K	0.999
1:11273847:G:C	D106H	0.999
1:11273848:A:C	D106A	0.999
1:11273848:A:G	D106G	0.999
1:11273848:A:T	D106V	0.999
1:11273849:C:A	D106E	0.999
1:11273849:C:G	D106E	0.999
1:11285657:G:C	K181N	0.999
1:11285657:G:T	K181N	0.999
1:11285818:G:T	R235M	0.999
1:11273828:T:A	N99K	0.998
1:11273828:T:G	N99K	0.998
1:11285656:A:T	K181M	0.998
1:11285674:A:C	D187A	0.998
1:11285694:T:C	F194L	0.998
1:11285696:T:A	F194L	0.998
1:11285696:T:G	F194L	0.998
1:11285813:C:A	N233K	0.998
1:11285813:C:G	N233K	0.998
1:11285818:G:C	R235T	0.998
1:11285821:A:C	D236A	0.998
1:11285821:A:T	D236V	0.998
1:11273733:G:C	G68R	0.997
1:11273734:G:A	G68D	0.997
1:11273839:C:T	T103I	0.997
1:11273847:G:A	D106N	0.997
1:11273850:T:C	F107L	0.997

dbSNP variants (sampled 300 via entrez): RS1000076072 (1:11292052 G>A,T), RS1000128241 (1:11291737 C>T), RS1000137152 (1:11277386 C>G), RS1000400646 (1:11292649 T>C), RS1000431694 (1:11273112 A>C), RS1000445016 (1:11275077 G>A), RS1000634858 (1:11276704 A>G), RS1000722528 (1:11280625 GTTCTT>G), RS1000810791 (1:11276570 A>G), RS1000899566 (1:11298809 T>C), RS1001066054 (1:11276440 G>A), RS1001083027 (1:11282073 A>G), RS1001442638 (1:11298236 G>A,T), RS1001454009 (1:11297997 G>A), RS1001533970 (1:11274823 T>C)

Disease associations

OMIM: gene MIM:611632 | disease phenotypes: MIM:121800

GenCC curated gene-disease

Disease	Classification	Inheritance
Schnyder corneal dystrophy	Definitive	Autosomal dominant

Mondo (2): Schnyder corneal dystrophy (MONDO:0007374), corneal dystrophy (MONDO:0018102)

Orphanet (2): Schnyder corneal dystrophy (Orphanet:98967), Corneal dystrophy (Orphanet:34533)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001131	Corneal dystrophy
HP:0007760	Crystalline corneal dystrophy

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003475_1	Beard thickness	4.000000e-07
GCST006412_32	Intraocular pressure	6.000000e-10
GCST008152_116	Weight	4.000000e-06
GCST010396_162	Gut microbiota (bacterial taxa, hurdle binary method)	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0004338	body weight
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003317	Corneal Dystrophies, Hereditary	C11.204.236; C11.270.162; C16.320.290.162
C535475	Corneal Dystrophy, Crystalline, of Schnyder (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation, decreases expression	2
Benzo(a)pyrene	increases expression	2
Estradiol	increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
bisphenol F	affects cotreatment, increases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
menatetrenone	increases chemical synthesis, increases metabolic processing	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
cylindrospermopsin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
monomethylarsonous acid	increases expression	1
Temozolomide	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cadmium	decreases expression, increases abundance	1
Calcitriol	increases expression	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Indomethacin	affects cotreatment, increases expression	1
Lead	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2N4	HAP1 UBIAD1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05279157	PHASE2	COMPLETED	Autologous Adipose-Derived Adult Stem Cell Implantation for Corneal Diseases (ADASCs-CT-CD)
NCT04484402	PHASE1/PHASE2	COMPLETED	Treatment of Patients With Inflammatory-dystrophic Diseases of the Cornea Using Autologous Stem Cells
NCT02932852	EARLY_PHASE1	UNKNOWN	Autologous Adipose-Derived Adult Stem Cell Transplantation for Corneal Diseases
NCT01084850	Not specified	UNKNOWN	Corneal Endothelium Morphology and Central Thickness in Type II Diabetes Mellitus and Normal Subjects
NCT02173847	Not specified	COMPLETED	Laser Assisted Procedures in Penetrating Keratoplasty
NCT02736877	Not specified	UNKNOWN	Corneal Transplantation Guided by OCT RESCAN
NCT02746055	Not specified	UNKNOWN	Study of the Prevalence of TGFBI Corneal Dystrophies
NCT03461991	Not specified	COMPLETED	Correlation Between In-vivo Anatomy of Corneal Dystrophies as Assessed by High- Resolution Optical Coherence Tomography (OCT) Measurement and Histological Examination
NCT03504800	Not specified	RECRUITING	OCT in Diagnosis of Irregular Corneas
NCT04129021	Not specified	RECRUITING	High Resolution, High-speed Multimodal Ophthalmic Imaging
NCT04164407	Not specified	UNKNOWN	Keratoconus, Corneal Diseases and Transplant Registry
NCT04384094	Not specified	UNKNOWN	Defining the Operating Parameters for a Rebound-esthesiometer
NCT04424550	Not specified	COMPLETED	Comparative Results After DSAEK, UT-DSAEK and DMEK for Fuchs Endothelial Corneal Dystophy
NCT05742321	Not specified	RECRUITING	Analysis of the Genotype/Phenotype Relationship in the Fuchs’ Corneal Endothelial Dystrophy in France
NCT05891106	Not specified	COMPLETED	AONDA Therapeutic Indication Study I
NCT05927740	Not specified	COMPLETED	The Efficacy of Hyperemesis Gravidarum on Macular Thickness, Corneal Thickness and Intraocular Pressure in Pregnancy
NCT05956535	Not specified	COMPLETED	Air Optix® Night and Day® Aqua Therapeutic Wear
NCT06491615	Not specified	RECRUITING	National Ophthalmic Genotyping and Phenotyping Network (eyeGENE (Registered Trademark)), Stage 3 - Expansion of DNA and Data Repositories for Rare Inherited Ophthalmic Diseases
NCT06844123	Not specified	RECRUITING	Microsurgical Robot-assisted Corneal Transplant
NCT06881771	Not specified	RECRUITING	FECD-TRACE: Fuchs’ Endothelial Corneal Dystrophy TRAjectory and Correlation With Genotype in the United Kingdom