NIT1

protein-coding

nitrilase 1

Gene summary

This gene encodes a member of the nitrilase protein family with homology to bacterial and plant nitrilases, enzymes that cleave nitriles and organic amides to the corresponding carboxylic acids plus ammonia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

MANE transcript

NM_005600.3

Inheritance

ClinVar variants

P:3U:72B:2

Top phenotype

cerebrovascular disorder

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr1:161,118,086-161,125,445

External References & Databases

Ensembl (ENSG00000158793)

Transcript & Mutation Effects

hg38 • Region Span ~7.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cerebrovascular disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011057

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NIT1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 72

Brain small vessel disease 4Total: 2

not providedTotal: 1

Susceptibility to severe COVID-19Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005600.3. 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			1 clinvar	1 clinvar		2
missense		1 clinvar	71 clinvar	1 clinvar		73
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	1	2	72	2	0	77

Highest pathogenic variant AF is 0.00022000523

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005600.3	RefSeq	NP_005591.1	7	MANE Select
ENST00000368009.7	Ensembl	ENSP00000356988.2	7	MANE Select
NM_001185092.2	RefSeq	NP_001172021.1	7	Standard
NM_001185093.2	RefSeq	NP_001172022.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

nitrogen compound metabolic process
biological_process

Molecular Function

nitrilase activity
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides

Cellular Component

nucleus
mitochondrion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368009
Coding exons: 7
Length: 7360
Individuals with no LoFs: 125648
Homozygous LoFs: 0
Heterozygous LoFs: 100
Defined: 125748
p: 0.000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.598	217	194	1.12	0.0000107	2086
Missense (PolyPhen)		57	57.244	0.99574		573
Synonymous	-0.426	76	71.4	1.06	0.00000346	712
Loss of Function	1.30	12	17.9	0.670	0.00000106	179

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.00062	0.00061	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00045	0.00045	rare
South Asian	0.00033	0.00033	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the hydrolysis of the amide bond in N-(4- oxoglutarate)-L-cysteinylglycine (deaminated glutathione), a metabolite repair reaction to dispose of the harmful deaminated glutathione. Plays a role in cell growth and apoptosis: loss of expression promotes cell growth, resistance to DNA damage stress and increased incidence to NMBA-induced tumors. Has tumor suppressor properties that enhances the apoptotic responsiveness in cancer cells; this effect is additive to the tumor suppressor activity of FHIT. It is also a negative regulator of primary T- cells. {ECO:0000250|UniProtKB:Q8VDK1}.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.137
RVIS EVS: 0.15
RVIS percentile EVS: 64.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.261

Gene Damage Prediction

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