ARL6IP1

ADP ribosylation factor like GTPase 6 interacting protein 1

Basic information

Region (hg38): 16:18791609-18801572

Previous symbols: [ "ARL6IP" ]

Links

ENSG00000170540 ∙ NCBI:23204 ∙ OMIM:607669 ∙ HGNC:697 ∙ Uniprot:Q15041 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spastic paraplegia 61 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 61 (Supportive), mode of inheritance: AR
• hereditary spastic paraplegia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia, autosomal recessive 61	AR	General	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	Neurologic	24482476

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARL6IP1 gene.

• Hereditary_spastic_paraplegia_61 (56 variants)
• Inborn_genetic_diseases (21 variants)
• not_provided (8 variants)
• ARL6IP1-related_disorder (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARL6IP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015161.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	13	2	16
missense	1		32	2	1	36
nonsense	2					2
start loss						0
frameshift		1				1
splice donor/acceptor (+/-2bp)		1				1
Total	3	2	33	15	3

Highest pathogenic variant AF is 0.0000111564395

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARL6IP1	protein_coding	protein_coding	ENST00000304414	6	10010

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0223	0.964	125725	0	20	125745	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	79	111	0.713	0.00000572	1313
Missense in Polyphen		12	17.981	0.66736		257
Synonymous	-0.722	45	39.2	1.15	0.00000210	391
Loss of Function	2.15	5	13.5	0.369	7.30e-7	135

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000442	0.000442
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000620	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000618	0.0000527
Middle Eastern	0.0000620	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Positively regulates SLC1A1/EAAC1-mediated glutamate transport by increasing its affinity for glutamate in a PKC activity-dependent manner. Promotes the catalytic efficiency of SLC1A1/EAAC1 probably by reducing its interaction with ARL6IP5, a negative regulator of SLC1A1/EAAC1-mediated glutamate transport (By similarity). Plays a role in the formation and stabilization of endoplasmic reticulum tubules (PubMed:24262037). Negatively regulates apoptosis, possibly by modulating the activity of caspase-9 (CASP9). Inhibits cleavage of CASP9-dependent substrates and downstream markers of apoptosis but not CASP9 itself (PubMed:12754298). May be involved in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation (PubMed:10995579). {ECO:0000250|UniProtKB:Q9JKW0, ECO:0000269|PubMed:12754298, ECO:0000269|PubMed:24262037, ECO:0000303|PubMed:10995579}.
• Disease: DISEASE: Spastic paraplegia 61, autosomal recessive (SPG61) [MIM:615685]: A complicated form of spastic paraplegia with polysensory and motor neuropathy. Spastic paraplegia is a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. {ECO:0000269|PubMed:24482476}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.633
• rvis_EVS: -0.14
• rvis_percentile_EVS: 42.88

Haploinsufficiency Scores

• pHI: 0.256
• hipred: N
• hipred_score: 0.326
• ghis: 0.667

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.955

Mouse Genome Informatics

• Gene name: Arl6ip1
• Phenotype: vision/eye phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype

Zebrafish Information Network

• Gene name: arl6ip1
• Affected structure: iridophore
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: positive regulation of L-glutamate import across plasma membrane;cotranslational protein targeting to membrane;apoptotic process;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;endoplasmic reticulum tubular network formation;endoplasmic reticulum tubular network membrane organization
• Cellular component: Sec61 translocon complex;endoplasmic reticulum membrane;cytosol;membrane;integral component of membrane;integral component of endoplasmic reticulum membrane
• Molecular function: protein binding;identical protein binding