RNH1

protein-coding

ribonuclease/angiogenin inhibitor 1

Gene summary

Placental ribonuclease inhibitor (PRI) is a member of a family of proteinaceous cytoplasmic RNase inhibitors that occur in many tissues and bind to both intracellular and extracellular RNases (summarized by Lee et al., 1988 [PubMed 3219362]). In addition to control of intracellular RNases, the inhibitor may have a role in the regulation of angiogenin (MIM 105850). Ribonuclease inhibitor, of 50,000 Da, binds to ribonucleases and holds them in a latent form. Since neutral and alkaline ribonucleases probably play a critical role in the turnover of RNA in eukaryotic cells, RNH may be essential for control of mRNA turnover; the interaction of eukaryotic cells with ribonuclease may be reversible in vivo.[supplied by OMIM, Jul 2010]

Previous symbols:

MANE transcript

NM_203387.3

Inheritance

ClinVar variants

U:99B:9

Top phenotype

Encephalopathy, acute, infection-induced, susceptibility to, 12

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr11:494,512-507,300

External References & Databases

Ensembl (ENSG00000023191)

Transcript & Mutation Effects

hg38 • Region Span ~12.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

encephalitis, acute, infection-induced, susceptibility to, 12MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957561

Submitter: G2P

encephalitis, acute, infection-induced, susceptibility to, 12STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957561

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Encephalopathy, acute, infection-induced, susceptibility to, 12AR

Manifestation: Allergy/Immunology/Infectious; Hematologic; Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 36935417; 37191094

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RNH1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 90

Encephalitis, acute, infection-induced, susceptibility to, 12Total: 8

not providedTotal: 6

RNH1-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_203387.3. 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			2 clinvar	4 clinvar		6
missense			88 clinvar	5 clinvar		93
nonsense			1 clinvar			1
start loss			1 clinvar			1
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	99	9	0	108

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 271 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_203387.3	RefSeq	NP_976321.1	9	MANE Select
ENST00000354420.7	Ensembl	ENSP00000346402.2	9	MANE Select
NM_002939.4	RefSeq	NP_002930.2	9	Standard
NM_203383.2	RefSeq	NP_976317.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

mRNA catabolic process
negative regulation of catalytic activity
regulation of angiogenesis

Molecular Function

protein binding
ribonuclease inhibitor activity

Cellular Component

nucleoplasm
cytosol
angiogenin-PRI complex
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000534797
Coding exons: 9
Length: 12789
Individuals with no LoFs: 125668
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125715
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0905	284	280	1.02	0.0000174	2945
Missense (PolyPhen)		70	80.657	0.86787		1013
Synonymous	-2.00	168	138	1.22	0.00000960	960
Loss of Function	0.804	17	21.0	0.811	0.00000105	214

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00022	0.00021	rare
South Asian	0.00049	0.00049	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and ANG. May play a role in redox homeostasis. {ECO:0000269|PubMed:12578357, ECO:0000269|PubMed:14515218, ECO:0000269|PubMed:17292889}.;

Recessive Scores

pRec: 0.408

Intolerance Scores

LoFtool: 0.704
RVIS EVS: -0.15
RVIS percentile EVS: 42.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.977

Gene Damage Prediction

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