ARL2BP

ADP ribosylation factor like GTPase 2 binding protein

Basic information

Region (hg38): 16:57245259-57253635

Previous symbols: [ "RP66" ]

Links

ENSG00000102931 ∙ NCBI:23568 ∙ OMIM:615407 ∙ HGNC:17146 ∙ Uniprot:Q9Y2Y0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa with or without situs inversus (Strong), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa with or without situs inversus (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 82 with or without situs inversus	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	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Ophthalmologic	23849777
Although described patients did not suffer from sequelae as severe as have been reported in other types of ciliary dyskinesia, similar medical interventions may in theory be warranted

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARL2BP gene.

• not provided (6 variants)
• Retinal dystrophy (2 variants)
• ARL2BP-related disorder (1 variants)
• Retinitis pigmentosa (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARL2BP gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				13		13
missense			42	1	1	44
nonsense	3					3
start loss						0
frameshift	4					4
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2				3
splice region		1	6	3		10
non coding				13	1	14
Total	8	2	42	27	2

Highest pathogenic variant AF is 0.0000394

Variants in ARL2BP

This is a list of pathogenic ClinVar variants found in the ARL2BP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-57245373-C-A			Uncertain significance (Nov 01, 2022)
16-57245373-C-G			Uncertain significance (Jul 01, 2022)
16-57245374-G-A			Uncertain significance (Jan 02, 2021)
16-57245381-A-G			Uncertain significance (Jul 19, 2022)
16-57245383-GGA-G		Retinitis pigmentosa with or without situs inversus	Pathogenic (Aug 27, 2024)
16-57245389-A-G			Uncertain significance (Jan 02, 2024)
16-57245394-T-A		Inborn genetic diseases	Uncertain significance (Jan 07, 2022)
16-57245397-GCTGT-G		Retinitis pigmentosa • Retinitis pigmentosa with or without situs inversus	Pathogenic (Jul 24, 2023)
16-57245399-T-C		Retinal dystrophy	Uncertain significance (Oct 01, 2023)
16-57245402-CTT-C		Retinal dystrophy	Pathogenic (Oct 01, 2023)
16-57245407-T-G		Retinitis pigmentosa	Pathogenic (Jun 23, 2019)
16-57245408-G-C			Uncertain significance (Mar 04, 2022)
16-57245417-C-T			Likely benign (Apr 27, 2021)
16-57245425-C-T			Likely benign (Mar 01, 2023)
16-57246066-G-T			Likely benign (Jul 12, 2022)
16-57246079-G-C			Likely pathogenic (Aug 22, 2023)
16-57246086-C-T			Likely benign (Dec 09, 2021)
16-57246087-G-T		Inborn genetic diseases	Uncertain significance (Oct 17, 2022)
16-57246098-A-G			Likely benign (Jan 21, 2023)
16-57246113-G-A			Likely benign (Sep 01, 2022)
16-57246115-T-A		Retinal dystrophy	Uncertain significance (Oct 01, 2023)
16-57246121-A-G			Uncertain significance (Jul 30, 2022)
16-57246126-G-A			Uncertain significance (Jun 23, 2022)
16-57246135-A-G			Uncertain significance (Apr 30, 2022)
16-57246138-A-G		Inborn genetic diseases	Uncertain significance (Jan 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARL2BP	protein_coding	protein_coding	ENST00000219204	6	8507

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000335	0.596	125695	0	53	125748	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.826	64	85.5	0.749	0.00000414	1075
Missense in Polyphen		10	20.007	0.49982		327
Synonymous	0.461	30	33.4	0.899	0.00000169	289
Loss of Function	0.755	8	10.7	0.751	6.29e-7	121

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000356	0.000346
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00103	0.00102
European (Non-Finnish)	0.000163	0.000149
Middle Eastern	0.0000544	0.0000544
South Asian	0.000143	0.000131
Other	0.000352	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. May play a role as an effector of ARL2. {ECO:0000269|PubMed:18234692}.
• Pathway: Metabolism;Regulation of insulin secretion;Integration of energy metabolism (Consensus)

Recessive Scores

• pRec: 0.0682

Intolerance Scores

• loftool: 0.709
• rvis_EVS: 0.13
• rvis_percentile_EVS: 62.74

Haploinsufficiency Scores

• pHI: 0.0483
• hipred: N
• hipred_score: 0.261
• ghis: 0.499

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Mouse Genome Informatics

• Gene name: Arl2bp

Gene ontology

• Biological process: signal transduction;positive regulation of tyrosine phosphorylation of STAT protein;regulation of catalytic activity;regulation of insulin secretion;maintenance of protein location in nucleus;positive regulation of nucleic acid-templated transcription
• Cellular component: nucleus;mitochondrial intermembrane space;mitochondrial matrix;centrosome;spindle;cytosol;cilium;midbody
• Molecular function: transcription coactivator activity;protein binding;GTPase regulator activity