ARV1

Summary

ARV1 (ARV1 fatty acid homeostasis modulator, HGNC:29561) is a protein-coding gene on chromosome 1q42.2, encoding Protein ARV1 (Q9H2C2). Plays a role as a mediator in the endoplasmic reticulum (ER) cholesterol and bile acid homeostasis.

this gene encodes a transmembrane protein that contains a conserved zinc ribbon motif at the N- terminus. A similar protein in mouse is thought to function in fatty acid homeostasis. Mutations in this gene are associated with early infantile epileptic encephalopathy 38.

Source: NCBI Gene 64801 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 38 (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 84 total — 4 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 20
• MANE Select transcript: NM_022786

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29561
Approved symbol	ARV1
Name	ARV1 fatty acid homeostasis modulator
Location	1q42.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000173409
Ensembl biotype	protein_coding
OMIM	611647
Entrez	64801

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000310256, ENST00000366658, ENST00000435927, ENST00000450711, ENST00000459891, ENST00000480519, ENST00000497753, ENST00000893838, ENST00000893839, ENST00000893840, ENST00000893841, ENST00000893842, ENST00000893843, ENST00000936179, ENST00000936180, ENST00000960456

RefSeq mRNA: 2 — MANE Select: NM_022786 NM_001346992, NM_022786

CCDS: CCDS1589

Canonical transcript exons

ENST00000310256 — 6 exons

Exon	Start	End
ENSE00001205613	230997121	230997267
ENSE00001442264	230979094	230979279
ENSE00003471569	230988320	230988439
ENSE00003473016	230990110	230990263
ENSE00003533772	230995760	230995984
ENSE00003849891	231000138	231000733

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 96.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.5990 / max 129.1825, expressed in 1786 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9042	13.5990	1786

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	96.99	gold quality
myocardium	UBERON:0002349	96.08	gold quality
left ventricle myocardium	UBERON:0006566	96.02	gold quality
parotid gland	UBERON:0001831	95.96	gold quality
upper arm skin	UBERON:0004263	95.39	gold quality
tibialis anterior	UBERON:0001385	95.28	gold quality
ileal mucosa	UBERON:0000331	94.94	gold quality
kidney epithelium	UBERON:0004819	94.31	gold quality
epithelial cell of pancreas	CL:0000083	94.21	gold quality
heart right ventricle	UBERON:0002080	94.18	gold quality
deltoid	UBERON:0001476	93.95	gold quality
pons	UBERON:0000988	93.86	gold quality
pancreatic ductal cell	CL:0002079	93.55	gold quality
vastus lateralis	UBERON:0001379	93.24	gold quality
quadriceps femoris	UBERON:0001377	93.09	gold quality
nasal cavity epithelium	UBERON:0005384	92.85	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.77	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.57	gold quality
spinal cord	UBERON:0002240	92.50	gold quality
biceps brachii	UBERON:0001507	92.35	gold quality
oocyte	CL:0000023	92.33	gold quality
subthalamic nucleus	UBERON:0001906	92.26	gold quality
rectum	UBERON:0001052	91.92	gold quality
lateral globus pallidus	UBERON:0002476	91.92	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.89	gold quality
adult organism	UBERON:0007023	91.72	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.69	gold quality
colonic mucosa	UBERON:0000317	91.62	gold quality
substantia nigra	UBERON:0002038	91.55	gold quality
nucleus accumbens	UBERON:0001882	91.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting ARV1, 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-6748-5P	100.00	65.81	1057
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-3150B-3P	98.81	67.21	1728

Literature-anchored findings (GeneRIF, showing 9)

• ARV1 plays a role in sphingolipid metabolism and complements yeast ARV1 (PMID:12145310)
• Arv1p has a role in sterol movement from the ER and in the ensuing regulation of hepatic cholesterol and bile acid metabolism (PMID:20663892)
• These results implicate ARV1 as a protective factor in lipotoxic diseases due to modulation of fatty acid metabolism. (PMID:24273168)
• Overexpression of human ARV1 could rescue the phenotypes associated with GPI anchor synthesis defect in the yeast arv1Delta mutant. Arv1 function in GPI biosynthesis may be conserved in all eukaryotes, from yeast to humans. (PMID:26460143)
• A novel function for Arv1 in regulation of cell division through promotion of the contractile actomyosin ring, which is independent of its lipid transporter activity. (PMID:27104745)
• In contrast to wild type human ARV1, neither variant expressed detectable levels of protein in mammalian cells. Mice with a neuronal deletion of Arv1 recapitulated the human phenotype, exhibiting seizures and a severe survival defect in adulthood. Our data support ARV1 deficiency as a cause of autosomal recessive epileptic encephalopathy (PMID:27270415)
• Homozygous splice-variants in human ARV1 cause GPI-anchor synthesis deficiency. (PMID:32165008)
• A defect in GPI synthesis as a suggested mechanism for the role of ARV1 in intellectual disability and seizures. (PMID:32462292)
• Epileptic encephalopathy caused by ARV1 deficiency: Refinement of the genotype-phenotype spectrum and functional impact on GPI-anchored proteins. (PMID:34296759)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	arv1	ENSDARG00000074757
mus_musculus	Arv1	ENSMUSG00000031982
rattus_norvegicus	Arv1	ENSRNOG00000018909
drosophila_melanogaster	Arv1	FBGN0052442
caenorhabditis_elegans		WBGENE00011040

Protein

Protein identifiers

Protein ARV1 — Q9H2C2 (reviewed: Q9H2C2)

All UniProt accessions (5): A0A0A0MRI7, Q9H2C2, H0YEB4, H7C0E7, H7C484

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role as a mediator in the endoplasmic reticulum (ER) cholesterol and bile acid homeostasis. Participates in sterol transport out of the ER and distribution into plasma membranes.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Ubiquitous. Highly expressed in liver and adipose.

Disease relevance. Developmental and epileptic encephalopathy 38 (DEE38) [MIM:617020] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE38 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. When transfected in S.cerevisiae, it can complement the absence of yeast of ARV1 protein, suggesting a conserved role in sphingolipid metabolism.

Similarity. Belongs to the ARV1 family.

RefSeq proteins (2): NP_001333921, NP_073623* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007290	Arv1	Family

Pfam: PF04161

UniProt features (9 total): transmembrane region 3, sequence variant 3, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H2C2-F1	82.17	0.50

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-191273	Cholesterol biosynthesis
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8957322	Metabolism of steroids

MSigDB gene sets: 214 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, MYOGENIN_Q6, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_CHOLESTEROL_EFFLUX, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_RESPONSE_TO_INSULIN, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION

GO Biological Process (13): sphingolipid metabolic process (GO:0006665), cholesterol biosynthetic process (GO:0006695), bile acid metabolic process (GO:0008206), sterol metabolic process (GO:0016125), cholesterol transport (GO:0030301), intracellular sterol transport (GO:0032366), regulation of intracellular cholesterol transport (GO:0032383), regulation of cholesterol metabolic process (GO:0090181), regulation of plasma membrane sterol distribution (GO:0097036), lipid metabolic process (GO:0006629), lipid transport (GO:0006869), steroid metabolic process (GO:0008202), cholesterol metabolic process (GO:0008203)

GO Molecular Function (2): sterol transfer activity (GO:0120015), protein binding (GO:0005515)

GO Cellular Component (5): endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cortical endoplasmic reticulum (GO:0032541), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of steroids	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sterol transport	3
lipid metabolic process	2
cholesterol metabolic process	2
steroid metabolic process	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
monocarboxylic acid metabolic process	1
intracellular anatomical structure	1
intracellular lipid transport	1
intracellular cholesterol transport	1
regulation of cholesterol transport	1
regulation of intracellular sterol transport	1
regulation of steroid metabolic process	1
regulation of small molecule metabolic process	1
plasma membrane organization	1
regulation of membrane lipid distribution	1
primary metabolic process	1
transport	1
lipid localization	1
sterol metabolic process	1
secondary alcohol metabolic process	1
sterol binding	1
lipid transfer activity	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cell cortex	1
endoplasmic reticulum tubular network	1
cellular anatomical structure	1

Protein interactions and networks

STRING

280 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARV1	PIGQ	Q9BRB3	532
ARV1	TEX2	Q8IWB9	457
ARV1	PIGH	Q14442	449
ARV1	PIGY	Q3MUY2	445
ARV1	PIGP	P57054	418
ARV1	PIGC	Q92535	416
ARV1	PIGK	Q92643	416
ARV1	PIGG	Q5H8A4	402
ARV1	PIGA	P37287	383
ARV1	DPM2	O94777	367
ARV1	DPM3	Q9P2X0	362
ARV1	INTS12	Q96CB8	355
ARV1	PIGM	Q9H3S5	353
ARV1	ERI1	Q8IV48	343
ARV1	DPM1	O60762	318

IntAct

101 interactions, top by confidence:

A	B	Type	Score
ARV1	SCN3B	psi-mi:“MI:0915”(physical association)	0.740
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
FAM234B	ABCD4	psi-mi:“MI:0914”(association)	0.620
	ARV1	psi-mi:“MI:0915”(physical association)	0.560
CREB3L1	ARV1	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	ARV1	psi-mi:“MI:0915”(physical association)	0.560
GPR152	ARV1	psi-mi:“MI:0915”(physical association)	0.560
RNASEK	ARV1	psi-mi:“MI:0915”(physical association)	0.560
TLCD4	ARV1	psi-mi:“MI:0915”(physical association)	0.560
SLC10A6	ARV1	psi-mi:“MI:0915”(physical association)	0.560
ARV1	TMX2	psi-mi:“MI:0915”(physical association)	0.560
AQP6	ARV1	psi-mi:“MI:0915”(physical association)	0.560
EBP	ARV1	psi-mi:“MI:0915”(physical association)	0.560
MUC1	ARV1	psi-mi:“MI:0915”(physical association)	0.560
ARV1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
CD4	CCDC85C	psi-mi:“MI:0914”(association)	0.530
SPRING1	PLSCR1	psi-mi:“MI:0914”(association)	0.530
SCN3B	ABCC5	psi-mi:“MI:0914”(association)	0.530
ACVR1	BMPR1A	psi-mi:“MI:0914”(association)	0.530

BioGRID (95): CREB1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS)

ESM2 similar proteins: A1L3F5, A2QRA0, A7MBC7, A8C750, A8MYZ0, A9JRL3, D3ZWZ9, F1M8G0, O14524, O17482, Q08DA4, Q0IJ20, Q29RL0, Q3B8G4, Q3SZW3, Q3TTL0, Q5BIY5, Q5BPL5, Q5MK23, Q5MK24, Q5RBY5, Q5RDB4, Q5SWK7, Q5U308, Q5VW38, Q5ZKN3, Q6AXN4, Q6DD21, Q6NXY1, Q6ZQE4, Q7L1W4, Q7SZC5, Q7ZWF4, Q7ZYA0, Q803Z2, Q8BGR2, Q8BUV8, Q8CB19, Q8N3S3, Q8NBN3

Diamond homologs: Q06541, Q3SZW3, Q54GD9, Q5ANH2, Q5MK23, Q5MK24, Q750Q7, Q9D0U9, Q9H2C2, Q9HDX5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 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
SLC-mediated transmembrane transport	8	8.9×	1e-03
Transport of small molecules	10	4.8×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
transmembrane transport	6	13.8×	3e-03
transport across blood-brain barrier	5	12.3×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	10
Uncertain significance	47
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
1343148	NM_022786.3(ARV1):c.175-3_175-2inv	Pathogenic
224496	NM_022786.3(ARV1):c.294+1G>A	Pathogenic
2473859	NM_022786.3(ARV1):c.148del (p.His50fs)	Pathogenic
3775589	NM_022786.3(ARV1):c.384del (p.Asp129fs)	Pathogenic
1028780	NM_022786.3(ARV1):c.175-2A>G	Likely pathogenic
1066297	NM_022786.3(ARV1):c.448+1G>T	Likely pathogenic
1339604	NM_022786.3(ARV1):c.2T>C (p.Met1Thr)	Likely pathogenic
183341	NM_022786.3(ARV1):c.565G>A (p.Gly189Arg)	Likely pathogenic
1878578	NM_022786.3(ARV1):c.573_574del (p.Leu192fs)	Likely pathogenic
2446533	NM_022786.3(ARV1):c.518del (p.Lys173fs)	Likely pathogenic
2663891	NM_022786.3(ARV1):c.594_595del (p.Ile198fs)	Likely pathogenic
817303	NM_022786.3(ARV1):c.517_518insC (p.Lys173fs)	Likely pathogenic
982604	NM_022786.3(ARV1):c.363_364del (p.Ser122fs)	Likely pathogenic
996783	NM_022786.3(ARV1):c.309_310del (p.Cys104fs)	Likely pathogenic

SpliceAI

1212 predictions. Top by Δscore:

Variant	Effect	Δscore
1:230979223:G:GT	donor_gain	1.0000
1:230979278:GT:G	donor_gain	1.0000
1:230979280:G:GG	donor_gain	1.0000
1:230988314:TTTCA:T	acceptor_loss	1.0000
1:230988315:TTCA:T	acceptor_loss	1.0000
1:230988316:TCAG:T	acceptor_loss	1.0000
1:230988317:CA:C	acceptor_loss	1.0000
1:230988318:A:AC	acceptor_loss	1.0000
1:230988318:A:AG	acceptor_gain	1.0000
1:230988319:G:GG	acceptor_gain	1.0000
1:230988319:GA:G	acceptor_gain	1.0000
1:230988319:GAA:G	acceptor_gain	1.0000
1:230988435:TAAAT:T	donor_gain	1.0000
1:230988436:AAAT:A	donor_gain	1.0000
1:230988436:AAATG:A	donor_loss	1.0000
1:230988437:AAT:A	donor_gain	1.0000
1:230988437:AATGT:A	donor_loss	1.0000
1:230988438:AT:A	donor_gain	1.0000
1:230988438:ATG:A	donor_loss	1.0000
1:230988439:TG:T	donor_loss	1.0000
1:230988440:G:GA	donor_loss	1.0000
1:230988440:G:GG	donor_gain	1.0000
1:230988441:T:TC	donor_loss	1.0000
1:230988442:A:AT	donor_loss	1.0000
1:230997119:A:AG	acceptor_gain	1.0000
1:230997119:AGT:A	acceptor_gain	1.0000
1:230997120:G:GG	acceptor_gain	1.0000
1:230997120:GT:G	acceptor_gain	1.0000
1:230997120:GTG:G	acceptor_gain	1.0000
1:230997120:GTGA:G	acceptor_gain	1.0000

AlphaMissense

1792 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:230988341:G:C	D66H	0.996
1:230979277:T:C	C58R	0.995
1:230988383:G:C	A80P	0.995
1:230988342:A:T	D66V	0.994
1:230988427:T:A	N94K	0.994
1:230988427:T:G	N94K	0.994
1:230990149:G:C	A112P	0.994
1:230995906:T:A	W199R	0.994
1:230995906:T:C	W199R	0.994
1:230979205:T:C	C34R	0.993
1:230979214:T:A	C37S	0.992
1:230979215:G:C	C37S	0.992
1:230979278:G:A	C58Y	0.992
1:230988342:A:C	D66A	0.992
1:230988415:T:A	H90Q	0.992
1:230988415:T:G	H90Q	0.992
1:230979205:T:A	C34S	0.991
1:230979206:G:C	C34S	0.991
1:230979214:T:C	C37R	0.991
1:230988343:C:A	D66E	0.991
1:230988343:C:G	D66E	0.991
1:230995877:G:A	G189E	0.991
1:230995895:C:G	P195R	0.991
1:230995908:G:C	W199C	0.991
1:230995908:G:T	W199C	0.991
1:230997169:G:A	G241D	0.991
1:230979277:T:A	C58S	0.990
1:230979278:G:C	C58S	0.990
1:230988355:G:C	E70D	0.990
1:230988355:G:T	E70D	0.990

dbSNP variants (sampled 300 via entrez): RS1000158508 (1:230999368 G>A), RS1000160939 (1:230982609 C>A,G), RS1000218663 (1:230982890 T>C), RS1000452691 (1:230987785 C>T), RS1000763722 (1:231001205 T>C), RS1000910969 (1:230994120 A>G), RS1000959790 (1:230981297 C>G), RS1001016320 (1:230987501 T>C), RS1001182196 (1:230992369 C>A), RS1001288984 (1:230999284 G>A), RS1001618794 (1:230987903 G>C), RS1001738518 (1:230998787 T>G), RS1002229705 (1:230979890 T>C), RS1002269198 (1:230977122 T>C), RS1002620152 (1:230989550 G>A)

Disease associations

OMIM: gene MIM:611647 | disease phenotypes: MIM:617020, MIM:616271

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 38	Strong	Autosomal recessive

Mondo (5): developmental and epileptic encephalopathy, 38 (MONDO:0014868), blindness (disorder) (MONDO:0001941), congenital nervous system disorder (MONDO:0002320), neurodegenerative disease (MONDO:0005559), 3-methylglutaconic aciduria, type VIIB (MONDO:0014561)

Orphanet (1): 3-methylglutaconic aciduria-neonatal cataract-neurologic involvement-congenital neutropenia syndrome (Orphanet:445038)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000556	Retinal dystrophy
HP:0000737	Irritability
HP:0001251	Ataxia
HP:0001332	Dystonia
HP:0002020	Gastroesophageal reflux
HP:0002033	Poor suck
HP:0002133	Status epilepticus
HP:0002187	Profound intellectual disability
HP:0002376	Developmental regression
HP:0002509	Limb hypertonia
HP:0002521	Hypsarrhythmia
HP:0002835	Aspiration
HP:0003593	Infantile onset
HP:0007843	Attenuation of retinal blood vessels
HP:0008499	High hypermetropia
HP:0008936	Axial hypotonia
HP:0012736	Profound global developmental delay
HP:0031165	Multifocal seizures
HP:0200134	Epileptic encephalopathy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_1773	Metabolite levels	6.000000e-06
GCST009391_1970	Metabolite levels	6.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0010478	fructose-1-phosphate measurement
EFO:0010479	fructose-6-phosphate measurement
EFO:0010484	glucose-1-phosphate measurement
EFO:0010485	glucose-6-phosphate measurement
EFO:0010541	trimethylamine-N-oxide measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001766	Blindness	C10.597.751.941.162; C11.966.075; C23.888.592.763.941.162
D019636	Neurodegenerative Diseases	C10.574

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Valproic Acid	affects expression, decreases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
bisphenol A	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Gallic Acid	decreases expression	1
Nickel	decreases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01662414	PHASE4	COMPLETED	Effect of Undenatured Cysteine-Rich Whey Protein Isolate (HMS 90®) in Patients With Parkinson’s Disease
NCT04871464	PHASE4	UNKNOWN	Role and Mechanism of Probiotics in Improving Motor Symptoms in Mild to Moderate Parkinson’s Disease
NCT05357612	PHASE4	RECRUITING	Characterization of the Serotonin 2A Receptor Selective PET Tracer [18F]MH.MZ in Patients With Neurodegenerative Diseases
NCT05508789	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Donanemab (LY3002813) in Participants With Early Symptomatic Alzheimer’s Disease (TRAILBLAZER-ALZ 5)
NCT05738486	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Different Donanemab (LY3002813) Dosing Regimens in Adults With Early Alzheimer’s Disease (TRAILBLAZER-ALZ 6)
NCT06111014	PHASE3	TERMINATED	Continuation Study for Latozinemab
NCT06672237	PHASE3	RECRUITING	A Phase 3 Study of NTLA-2001 in ATTRv-PN
NCT00001365	PHASE2	COMPLETED	Dextromethorphan for the Treatment of Parkinson’s Disease and Similar Conditions of the Nervous System
NCT00406029	PHASE2	COMPLETED	Dyskinesia in Parkinson’s Disease (Study P04501)
NCT00537017	PHASE2	COMPLETED	Follow Up Safety Study of SCH 420814 in Subjects With Parkinson’s Disease (P05175)
NCT00907283	PHASE2	UNKNOWN	Ferrochelating Treatment in Patients Affected by Neurodegeneration With Brain Iron Accumulation (NBIA)
NCT01518374	PHASE2	COMPLETED	Clinical Evaluation of Florbetapir F 18 (18F-AV-45)
NCT02656498	PHASE2	COMPLETED	[18F]THK-5351 Positron Emission Computed Tomography Study of Normal, Mild Cognitive Impairment, Alzheimer’s Disease and Other Neurodegenerative Disease
NCT03127514	PHASE2	COMPLETED	AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT03538522	PHASE2	COMPLETED	A Double-Blind, Placebo-Controlled Safety and Efficacy Study of NA-831
NCT04838301	PHASE2	RECRUITING	Allopregnanolone Regenerative Therapeutic for Mild Alzheimer’s Disease
NCT04937452	PHASE2	COMPLETED	Dopaminergic Therapy for Frontotemporal Dementia Patients
NCT05318976	PHASE2	COMPLETED	A Study of XPro1595 in Patients With Early Alzheimer’s Disease With Biomarkers of Inflammation
NCT05321498	PHASE2	WITHDRAWN	Study to Assess the Efficacy of XPro1595 in Patients With Mild Cognitive Impairment With Biomarkers of Inflammation
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT05522387	PHASE2	TERMINATED	An Open-Label Extension of XPro1595 in Patients With Alzheimer’s Disease
NCT00316797	PHASE1	COMPLETED	Biodistribution and Safety of a Radiopharmaceutical in Healthy Subjects
NCT01758510	PHASE1	COMPLETED	Safety Study of HLA-haplo Matched Allogenic Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis
NCT02267434	PHASE1	COMPLETED	Study Assessing Tolerability and Safety of AFFITOPE® PD03A in Patients With Early Parkinson’s Disease
NCT02270489	PHASE1	COMPLETED	Study Assessing Safety and Therapeutic Activity of AFFITOPE® PD01A and PD03A in Patients With Early MSA
NCT03065192	PHASE1	COMPLETED	Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson’s Disease
NCT04578028	PHASE1	COMPLETED	A First in Human Study to Assess the Safety, Tolerability and Pharmacokinetics of ONO-2808-01 in Healthy Participants
NCT05143463	PHASE1	COMPLETED	A FIH Study to Assess the Safety and Tolerability of NS Intravenous NS101 Infusion
NCT05490576	PHASE1	UNKNOWN	Tau And Connectomics In TES Study
NCT05792163	PHASE1	COMPLETED	A First Time in Human Study of SNP318 as a Treatment for Neurodegenerative Diseases Including Alzheimer’s Disease
NCT07232147	PHASE1	NOT_YET_RECRUITING	Clinical Research on Stem Cell Therapy for Parkinson’s Disease
NCT03143374	PHASE2/PHASE3	RECRUITING	PET Tau - Neurodegenerative Disease Imaging
NCT06122662	PHASE2/PHASE3	COMPLETED	AMX0035 and Progressive Supranuclear Palsy
NCT03295786	PHASE1/PHASE2	COMPLETED	Clinical Study to Test the Safety of CDNF by Brain Infusion in Patients With Parkinson’s Disease
NCT05853471	PHASE1/PHASE2	UNKNOWN	[18F]MC225-PET in Neurodegenerative Disease
NCT06447194	PHASE1/PHASE2	WITHDRAWN	Effect of RECK in Posterior Spinal Fusion
NCT06934720	PHASE1/PHASE2	NOT_YET_RECRUITING	VR-based Physical Activity and Reminiscence Therapy
NCT02452216	EARLY_PHASE1	COMPLETED	Using Ferumoxytol-Enhanced MRI to Measure Inflammation in Patients With Brain Tumors or Other Conditions of the CNS
NCT04575727	EARLY_PHASE1	COMPLETED	Exploratory Evaluation of [11C]MPC6827
NCT06181513	EARLY_PHASE1	RECRUITING	Probiotics in Mild Alzheimer’s Disease