RNASE4

ribonuclease A family member 4, the group of Ribonuclease A family

Basic information

Region (hg38): 14:20684559-20701216

Links

ENSG00000258818 ∙ NCBI:6038 ∙ OMIM:601030 ∙ HGNC:10047 ∙ Uniprot:P34096 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNASE4 gene.

• not provided (45 variants)
• Amyotrophic lateral sclerosis type 9 (25 variants)
• Inborn genetic diseases (15 variants)
• not specified (6 variants)
• ANG-related condition (5 variants)
• Amyotrophic lateral sclerosis (1 variants)
• Frontotemporal dementia (1 variants)
• Amyotrophic lateral sclerosis type 10 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNASE4 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						0
missense			3			3
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding		1	36	17	7	61
Total	0	1	39	17	7

Highest pathogenic variant AF is 0.00000657

Variants in RNASE4

This is a list of pathogenic ClinVar variants found in the RNASE4 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-20684609-A-G		Amyotrophic lateral sclerosis type 9	Uncertain significance (Apr 27, 2017)
14-20684662-G-C		Amyotrophic lateral sclerosis type 9	Uncertain significance (Jan 13, 2018)
14-20684736-T-C		Amyotrophic lateral sclerosis type 9	Benign (Jan 13, 2018)
14-20684769-A-C		Amyotrophic lateral sclerosis type 9	Likely benign (Jan 12, 2018)
14-20693222-A-G			Benign (Jul 03, 2018)
14-20693226-T-G			Benign (Aug 11, 2018)
14-20693325-G-C			Benign (Aug 17, 2018)
14-20693471-G-A			Likely benign (May 26, 2019)
14-20693543-G-A		Amyotrophic lateral sclerosis type 9	Uncertain significance (Jan 13, 2018)
14-20693567-G-A		Amyotrophic lateral sclerosis type 9 • Amyotrophic lateral sclerosis type 10 • ANG-related disorder	Conflicting classifications of pathogenicity (Feb 15, 2024)
14-20693600-C-T		Inborn genetic diseases	Likely benign (Mar 14, 2024)
14-20693600-C-CGTGCTG			Uncertain significance (Nov 17, 2023)
14-20693602-T-C		Amyotrophic lateral sclerosis type 9	Uncertain significance (Apr 27, 2017)
14-20693617-T-A			Uncertain significance (Oct 01, 2017)
14-20693625-C-T		ANG-related disorder	Uncertain significance (Nov 27, 2023)
14-20693626-C-A		Amyotrophic lateral sclerosis type 9	Benign/Likely benign (Apr 20, 2022)
14-20693626-C-T		Amyotrophic lateral sclerosis type 9	Uncertain significance (Jan 26, 2022)
14-20693649-A-G			Uncertain significance (Jun 19, 2022)
14-20693658-C-T			Uncertain significance (Jun 01, 2016)
14-20693660-C-A		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
14-20693663-C-T		Amyotrophic lateral sclerosis type 9 • Inborn genetic diseases	Benign/Likely benign (Nov 06, 2023)
14-20693669-C-G			Likely benign (Apr 02, 2022)
14-20693671-A-T		Amyotrophic lateral sclerosis type 9	Pathogenic (Apr 01, 2006)
14-20693674-A-G			Uncertain significance (Oct 17, 2022)
14-20693675-C-T			Likely benign (Aug 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNASE4	protein_coding	protein_coding	ENST00000555835	1	16503

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000176	0.280	125721	1	23	125745	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0318	89	88.2	1.01	0.00000549	967
Missense in Polyphen		23	27.55	0.83484		357
Synonymous	-1.22	42	33.0	1.27	0.00000184	291
Loss of Function	-0.527	5	3.88	1.29	2.52e-7	41

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000132	0.000123
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This RNase has marked specificity towards the 3' side of uridine nucleotides.

Intolerance Scores

• rvis_EVS: 0.93
• rvis_percentile_EVS: 89.66

Haploinsufficiency Scores

• pHI: 0.0547
• hipred: N
• hipred_score: 0.170

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.983

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rnase4

Gene ontology

• Biological process: mRNA cleavage;RNA phosphodiester bond hydrolysis, endonucleolytic
• Cellular component: extracellular region
• Molecular function: nucleic acid binding;ribonuclease A activity;ribonuclease activity