RNASE6

protein-coding

ribonuclease A family member k6, the group of Ribonuclease A family

Gene summary

The protein encoded by this gene is a member of the ribonuclease A superfamily and functions in the urinary tract. The protein has broad-spectrum antimicrobial activity against pathogenic bacteria. [provided by RefSeq, Nov 2014]

Previous symbols:

RNS6

MANE transcript

NM_005615.5

Inheritance

—

ClinVar variants

U:20B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.25

Max pathogenic AF

—

Genomic locus

chr14:20,781,268-20,782,467

External References & Databases

Ensembl (ENSG00000169413)

Transcript & Mutation Effects

hg38 • Region Span ~1.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RNASE6 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 22

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005615.5. 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						0
missense			20 clinvar	2 clinvar		22
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	20	2	0	22

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005615.5	RefSeq	NP_005606.1	1	MANE Select
ENST00000304677.3	Ensembl	ENSP00000302046.2	1	MANE Select
ENST00000905521.1	Ensembl	ENSP00000575580.1	1	Standard
ENST00000905521.2	Ensembl	ENSP00000575580.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TYROBP Causal Network
Antimicrobial peptides
Innate Immune System
Immune System

Biological Process

RNA catabolic process
defense response
antimicrobial humoral response
antibacterial humoral response
innate immune response

Molecular Function

nucleic acid binding
endonuclease activity
ribonuclease activity

Cellular Component

extracellular region
extracellular space
lysosome
cytoplasmic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304677
Coding exons: 1
Length: 1417
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125739
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.233	87	81.1	1.07	0.00000397	994
Missense (PolyPhen)		27	27.398	0.98548		381
Synonymous	-0.0667	29	28.5	1.02	0.00000129	284
Loss of Function	-0.210	1	0.798	1.25	3.48e-8	6

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ribonuclease which shows a preference for the pyrimidines uridine and cytosine (PubMed:8836175, PubMed:27013146). Has potent antibacterial activity against a range of Gram-positive and Gram-negative bacteria, including P.aeruginosa, A.baumanii, M.luteus, S.aureus, E.faecalis, E.faecium, S.saprophyticus and E.coli (PubMed:25075772, PubMed:27089320). Causes loss of bacterial membrane integrity, and also promotes agglutination of Gram-negative bacteria (PubMed:27089320). Probably contributes to urinary tract sterility (PubMed:25075772). Bactericidal activity is independent of RNase activity (PubMed:27089320). {ECO:0000269|PubMed:25075772, ECO:0000269|PubMed:27013146, ECO:0000269|PubMed:27089320, ECO:0000269|PubMed:8836175}.;

Recessive Scores

pRec: 0.0867

Intolerance Scores

LoFtool: 0.812
RVIS EVS: 0.35
RVIS percentile EVS: 73.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.686

Gene Damage Prediction

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