NUDT21

protein-coding

nudix hydrolase 21, the group of Nudix hydrolase family|Cleavage factor Im complex subunits

Gene summary

The protein encoded by this gene is one subunit of a cleavage factor required for 3' RNA cleavage and polyadenylation processing. The interaction of the protein with the RNA is one of the earliest steps in the assembly of the 3' end processing complex and facilitates the recruitment of other processing factors. This gene encodes the 25kD subunit of the protein complex, which is composed of four polypeptides. [provided by RefSeq, Jul 2008]

Previous symbols:

CPSF5

MANE transcript

NM_007006.3

Inheritance

—

ClinVar variants

U:5B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr16:56,429,133-56,452,199

External References & Databases

Ensembl (ENSG00000167005)

Transcript & Mutation Effects

hg38 • Region Span ~23.1 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 NUDT21 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 5

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007006.3. 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	2
missense			5 clinvar			5
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	5	0	2	7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007006.3	RefSeq	NP_008937.1	7	MANE Select
ENST00000300291.10	Ensembl	ENSP00000300291.5	7	MANE Select
ENST00000566340.5	Ensembl	ENSP00000454790.1	5	Standard
ENST00000568822.1	Ensembl	ENSP00000457942.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mRNA surveillance pathway - Homo sapiens (human)
mRNA Processing
Gene expression (Transcription)
RNA Polymerase II Transcription
Metabolism of RNA

Biological Process

mRNA splicing, via spliceosome
termination of RNA polymerase II transcription
mRNA polyadenylation
mRNA processing
posttranscriptional regulation of gene expression

Molecular Function

chromatin binding
RNA binding
mRNA binding
protein binding
hydrolase activity

Cellular Component

nucleus
nucleoplasm
cytoplasm
centrosome
microtubule organizing center

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000300291
Coding exons: 7
Length: 23067
Individuals with no LoFs: 125743
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125745
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.47	15	124	0.121	0.00000607	1477
Missense (PolyPhen)		2	41.76	0.047893		585
Synonymous	-1.36	56	44.5	1.26	0.00000213	435
Loss of Function	3.33	0	12.9	0.00	5.44e-7	159

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs (PubMed:9659921, PubMed:8626397, PubMed:14690600, PubMed:15937220, PubMed:17024186, PubMed:17098938, PubMed:29276085). CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals) (PubMed:9659921, PubMed:8626397, PubMed:14690600, PubMed:17024186). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation (PubMed:17098938, PubMed:23187700, PubMed:29276085). The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'- untranslated region (UTR) for a huge number of pre-mRNAs (PubMed:17098938, PubMed:20695905, PubMed:29276085). NUDT21/CPSF5 activates indirectly the mRNA 3'-processing machinery by recruiting CPSF6 and/or CPSF7 (PubMed:29276085). Binds to 5'-UGUA- 3' elements localized upstream of pA signals that act as enhancers of pre-mRNA 3'-end processing (PubMed:8626397, PubMed:14690600, PubMed:15169763, PubMed:17024186, PubMed:22813749, PubMed:20479262). The homodimer mediates simultaneous sequence- specific recognition of two 5'-UGUA-3' elements within the pre- mRNA (PubMed:20479262, PubMed:21295486). Plays a role in somatic cell fate transitions and pluripotency by regulating widespread changes in gene expression through an APA-dependent function (By similarity). Binds to chromatin (By similarity). Binds to, but does not hydrolyze mono- and di-adenosine nucleotides (PubMed:18445629). {ECO:0000250|UniProtKB:Q9CQF3, ECO:0000269|PubMed:14690600, ECO:0000269|PubMed:15169763, ECO:0000269|PubMed:15937220, ECO:0000269|PubMed:17024186, ECO:0000269|PubMed:17098938, ECO:0000269|PubMed:18445629, ECO:0000269|PubMed:20479262, ECO:0000269|PubMed:20695905, ECO:0000269|PubMed:21295486, ECO:0000269|PubMed:22813749, ECO:0000269|PubMed:23187700, ECO:0000269|PubMed:29276085, ECO:0000269|PubMed:8626397, ECO:0000269|PubMed:9659921}.;

Recessive Scores

pRec: 0.136

Intolerance Scores

RVIS EVS: -0.01
RVIS percentile EVS: 52.85

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.964