RANGRF

RAN guanine nucleotide release factor

Basic information

Region (hg38): 17:8288654-8290092

Links

ENSG00000108961 ∙ NCBI:29098 ∙ OMIM:607954 ∙ HGNC:17679 ∙ Uniprot:Q9HD47 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Brugada syndrome (Limited), mode of inheritance: AD
• Brugada syndrome (Disputed Evidence), mode of inheritance: AD
• Brugada syndrome (Limited), mode of inheritance: Unknown

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RANGRF 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			2	28	3	33
missense			62	6		68
nonsense			3	2		5
start loss			1			1
frameshift			5			5
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			2	4		6
non coding			1	22	3	26
Total	0	0	76	58	6

Variants in RANGRF

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

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

Position	Type	Phenotype	Significance	ClinVar
17-8288744-A-C		not specified	Likely benign (Dec 22, 2016)
17-8288770-A-C		not specified	Likely benign (Jan 11, 2017)
17-8288787-C-T			Likely benign (Oct 24, 2022)
17-8288790-T-A		Cardiac arrhythmia	Uncertain significance (Jun 01, 2021)
17-8288793-A-G		Cardiac arrhythmia	Uncertain significance (Oct 22, 2023)
17-8288799-C-G		Cardiac arrhythmia	Uncertain significance (Jul 25, 2022)
17-8288799-CGA-C		Cardiac arrhythmia	Uncertain significance (Mar 03, 2023)
17-8288800-G-A		Cardiac arrhythmia	Likely benign (Jul 07, 2023)
17-8288802-G-A		not specified	Uncertain significance (Aug 17, 2024)
17-8288808-G-T		Cardiac arrhythmia	Uncertain significance (Apr 16, 2023)
17-8288809-C-T		Cardiac arrhythmia	Likely benign (Jun 14, 2022)
17-8288815-G-C		Cardiac arrhythmia	Likely benign (Jan 24, 2024)
17-8288823-G-A		Cardiac arrhythmia	Uncertain significance (Jul 05, 2022)
17-8288838-T-A		Cardiac arrhythmia	Uncertain significance (Nov 27, 2023)
17-8288840-C-A		Cardiac arrhythmia	Uncertain significance (Sep 24, 2020)
17-8288840-C-T		Cardiac arrhythmia	Uncertain significance (Jan 02, 2024)
17-8288845-C-T		Cardiac arrhythmia	Likely benign (Dec 31, 2023)
17-8288846-A-T		Cardiac arrhythmia	Uncertain significance (Dec 28, 2018)
17-8288847-T-C		Cardiac arrhythmia	Uncertain significance (Mar 07, 2021)
17-8288847-T-TG		Cardiac arrhythmia	Uncertain significance (Sep 10, 2020)
17-8288855-A-G		Cardiac arrhythmia	Uncertain significance (Jan 06, 2024)
17-8288863-A-T		Cardiac arrhythmia	Likely benign (Dec 19, 2023)
17-8288870-G-A		Cardiac arrhythmia	Uncertain significance (May 07, 2024)
17-8288873-G-A		Cardiac arrhythmia	Likely benign (Aug 04, 2023)
17-8288876-C-A		not specified	Likely benign (Dec 27, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RANGRF	protein_coding	protein_coding	ENST00000226105	5	1596

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000244	0.527	124733	5	1010	125748	0.00404

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.223	109	103	1.06	0.00000519	1210
Missense in Polyphen		39	38.196	1.0211		492
Synonymous	0.208	40	41.7	0.959	0.00000231	378
Loss of Function	0.622	8	10.1	0.789	5.46e-7	97

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00197	0.00196
Ashkenazi Jewish	0.000200	0.000198
East Asian	0.000109	0.000109
Finnish	0.0109	0.0108
European (Non-Finnish)	0.00574	0.00562
Middle Eastern	0.000109	0.000109
South Asian	0.00176	0.00177
Other	0.00573	0.00572

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May regulate the intracellular trafficking of RAN (PubMed:11290418). Promotes guanine nucleotide release from RAN and inhibits binding of new GTP by preventing the binding of the RAN guanine nucleotide exchange factor RCC1 (PubMed:29040603). Regulates the levels of GTP-bound RAN in the nucleus, and thereby plays a role in the regulation of RAN-dependent mitotic spindle dynamics (PubMed:29040603). Enhances the expression of SCN5A at the cell membrane in cardiomyocytes (PubMed:18184654, PubMed:23420830, PubMed:21621375). {ECO:0000269|PubMed:11290418, ECO:0000269|PubMed:18184654, ECO:0000269|PubMed:21621375, ECO:0000269|PubMed:23420830, ECO:0000269|PubMed:29040603}.
• Pathway: Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.465
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.58

Haploinsufficiency Scores

• pHI: 0.114
• hipred: Y
• hipred_score: 0.556
• ghis: 0.377

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.750

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rangrf

Zebrafish Information Network

• Gene name: rangrf
• Affected structure: heart contraction
• Phenotype tag: abnormal
• Phenotype quality: decreased rate

Gene ontology

• Biological process: regulation of heart rate;regulation of membrane depolarization;endoplasmic reticulum to Golgi vesicle-mediated transport;protein exit from endoplasmic reticulum;regulation of membrane potential;regulation of microtubule nucleation by Ran protein signal transduction;regulation of bundle of His cell action potential;regulation of cardiac muscle cell action potential involved in regulation of contraction;regulation of membrane depolarization during cardiac muscle cell action potential;regulation of sodium ion transmembrane transport;positive regulation of protein localization to plasma membrane;positive regulation of protein localization to cell surface;regulation of sodium ion transmembrane transporter activity
• Cellular component: nucleus;nucleoplasm;cytoplasm;rough endoplasmic reticulum;cytosol;plasma membrane;caveola;intercalated disc;perinuclear region of cytoplasm
• Molecular function: guanyl-nucleotide exchange factor activity;Ran guanyl-nucleotide exchange factor activity;Ran GTPase binding;protein transporter activity;sodium channel regulator activity;ion channel binding