ARV1

protein-coding

ARV1 homolog, fatty acid homeostasis modulator

Gene summary

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. [provided by RefSeq, Nov 2016]

MANE transcript

NM_022786.3

Inheritance

ClinVar variants

P:19U:47B:14

Top phenotype

Developmental and epileptic encephalopathy 38

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr1:230,978,981-231,000,733

External References & Databases

Ensembl (ENSG00000173409)

Transcript & Mutation Effects

hg38 • Region Span ~21.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental and epileptic encephalopathy, 38STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014868

Submitter: Labcorp Genetics (formerly Invitae)

developmental and epileptic encephalopathy, 38STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014868

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Developmental and epileptic encephalopathy 38AR

Manifestation: Neurologic

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: 25558065; 27270415

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARV1 variants in ClinVar

10 Conditions Cataloged

Inborn genetic diseasesTotal: 37

not providedTotal: 26

Developmental and epileptic encephalopathy, 38Total: 21

ARV1-related disorderTotal: 10

not specifiedTotal: 7

3-methylglutaconic aciduria, type VIIBTotal: 2

Abnormality of the nervous systemTotal: 1

NeurodegenerationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022786.3. 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			2 clinvar	7 clinvar		9
missense		1 clinvar	43 clinvar	6 clinvar	1 clinvar	51
nonsense		1 clinvar				1
start loss		1 clinvar				1
frameshift	4 clinvar	7 clinvar				11
splice donor/acceptor (+/-2bp)	2 clinvar	3 clinvar	2 clinvar			7
Total	6	13	47	13	1	80

Highest pathogenic variant AF is 0.0000745529

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022786.3	RefSeq	NP_073623.1	5	MANE Select
ENST00000310256.7	Ensembl	ENSP00000312458.2	5	MANE Select
NM_001346992.2	RefSeq	NP_001333921.1	6	Standard
ENST00000366658.6	Ensembl	ENSP00000355618.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of lipids
Metabolism
Metabolism of steroids
Cholesterol biosynthesis

Biological Process

sphingolipid metabolic process
cholesterol biosynthetic process
bile acid metabolic process
sterol metabolic process
cholesterol transport

Molecular Function

sterol transporter activity

Cellular Component

endoplasmic reticulum membrane
Golgi apparatus
integral component of membrane
cortical endoplasmic reticulum

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310256
Coding exons: 5
Length: 21615
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125748
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.192	139	146	0.955	0.00000699	1783
Missense (PolyPhen)		50	52.429	0.95368		700
Synonymous	0.390	54	57.8	0.935	0.00000293	501
Loss of Function	0.886	10	13.5	0.740	5.73e-7	169

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.000066	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role as a mediator in the endoplasmic reticulum (ER) cholesterol and bile acid homeostasis (PubMed:11063737, PubMed:12145310, PubMed:20663892). Participates in sterol transport out of the ER and distribution into plasma membranes (PubMed:20663892). {ECO:0000269|PubMed:11063737, ECO:0000269|PubMed:12145310, ECO:0000269|PubMed:20663892}.;

Intolerance Scores

LoFtool: 0.769
RVIS EVS: 0.33
RVIS percentile EVS: 73.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.766