Mutagenetix > Incidental Mutation

Incidental Mutation 'NA:Pcna'

618

Institutional Source

Beutler Lab

Gene Symbol

Pcna

Ensembl Gene

ENSMUSG00000027342

Gene Name

proliferating cell nuclear antigen

Synonyms

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

NA (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

132091206-132095100 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 132091804 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Threonine at position 199 (M199T)

Ref Sequence

ENSEMBL: ENSMUSP00000028817 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028816] [ENSMUST00000028817] [ENSMUST00000110163] [ENSMUST00000110164] [ENSMUST00000180286]

AlphaFold

P17918

Predicted Effect

probably benign
Transcript: ENSMUST00000028816

SMART Domains

Protein: ENSMUSP00000028816
Gene: ENSMUSG00000027341

Domain	Start	End	E-Value	Type
Pfam:DUF872	14	118	5.5e-30	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000028817
AA Change: M199T

PolyPhen 2 Score 0.009 (Sensitivity: 0.96; Specificity: 0.77)

SMART Domains

Protein: ENSMUSP00000028817
Gene: ENSMUSG00000027342
AA Change: M199T

Domain	Start	End	E-Value	Type
Pfam:PCNA_N	1	125	1.4e-61	PFAM
Pfam:Rad1	1	236	2e-10	PFAM
Pfam:Rad9	12	245	1.3e-9	PFAM
Pfam:PCNA_C	127	254	8.2e-66	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000110163

SMART Domains

Protein: ENSMUSP00000105792
Gene: ENSMUSG00000027341

Domain	Start	End	E-Value	Type
Pfam:DUF872	14	118	5.5e-30	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000110164

SMART Domains

Protein: ENSMUSP00000105793
Gene: ENSMUSG00000027341

Domain	Start	End	E-Value	Type
Pfam:DUF872	14	118	5.5e-30	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000124336

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135181

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000136676

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000143782

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000141813

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000149627

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000140338

Predicted Effect

probably benign
Transcript: ENSMUST00000180286

SMART Domains

Protein: ENSMUSP00000136826
Gene: ENSMUSG00000027341

Domain	Start	End	E-Value	Type
Pfam:DUF872	3	118	1.7e-22	PFAM

Meta Mutation Damage Score

0.3854

Coding Region Coverage

1x: 83.4%
3x: 67.1%

Het Detection Efficiency

45.4%

Validation Efficiency

80% (107/134)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene. Pseudogenes of this gene have been described on chromosome 4 and on the X chromosome. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit complete embryonic lethality before implantation due to defects in DNA replication. Mice homozygous for a knock-in allele show partial embryonic lethality during organogenesis, absent germ cells, infertility, and altered somatic hypermutation frequency. [provided by MGI curators]

Allele List at MGI

All alleles(7) : Targeted, knock-out(1) Targeted, other(4) Gene trapped(2)

Other mutations in this stock

Total: 7 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Cep350	G	A	1: 155,834,394 (GRCm39)	S101F	probably damaging	Het
Ctnnal1	C	T	4: 56,817,044 (GRCm39)	V593I	probably benign	Het
Ftsj3	C	A	11: 106,145,634 (GRCm39)	M66I	possibly damaging	Het
Igf2r	C	T	17: 12,910,849 (GRCm39)	V1990I	probably benign	Het
Kansl1	G	A	11: 104,233,193 (GRCm39)	T778I	probably benign	Het
Mast4	G	A	13: 102,878,565 (GRCm39)	T1031I	probably damaging	Het
Trip11	C	T	12: 101,860,580 (GRCm39)		probably null	Het

Other mutations in Pcna

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00435:Pcna	APN	2	132,093,852 (GRCm39)	missense	probably benign	0.12
IGL00839:Pcna	APN	2	132,093,340 (GRCm39)	missense	probably benign	0.00
IGL01463:Pcna	APN	2	132,093,349 (GRCm39)	missense	probably damaging	1.00
IGL02437:Pcna	APN	2	132,093,155 (GRCm39)	unclassified	probably benign
IGL03083:Pcna	APN	2	132,093,673 (GRCm39)	missense	probably benign	0.10
IGL03084:Pcna	APN	2	132,093,673 (GRCm39)	missense	probably benign	0.10
IGL03094:Pcna	APN	2	132,093,673 (GRCm39)	missense	probably benign	0.10
IGL03124:Pcna	APN	2	132,093,673 (GRCm39)	missense	probably benign	0.10
IGL03046:Pcna	UTSW	2	132,093,673 (GRCm39)	missense	probably benign	0.10
R0722:Pcna	UTSW	2	132,093,155 (GRCm39)	unclassified	probably benign
R1928:Pcna	UTSW	2	132,093,817 (GRCm39)	unclassified	probably benign
R3857:Pcna	UTSW	2	132,091,541 (GRCm39)	missense	probably benign	0.00
R7211:Pcna	UTSW	2	132,091,792 (GRCm39)	missense	probably damaging	1.00
R7296:Pcna	UTSW	2	132,094,797 (GRCm39)	missense	probably benign	0.10
R7917:Pcna	UTSW	2	132,094,929 (GRCm39)	missense	probably benign	0.03
R8318:Pcna	UTSW	2	132,093,348 (GRCm39)	missense	probably damaging	0.98
R8411:Pcna	UTSW	2	132,093,850 (GRCm39)	missense	probably benign
R8793:Pcna	UTSW	2	132,093,193 (GRCm39)	missense	probably benign	0.06
R8965:Pcna	UTSW	2	132,094,769 (GRCm39)	missense	possibly damaging	0.94
R9780:Pcna	UTSW	2	132,094,794 (GRCm39)	missense	probably benign	0.17

Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to C transition at position 740 of the Pcna transcript in exon 5 of 6 exons using Genbank record NM_011045.2. Multiple transcripts of the Pcna gene are displayed on Ensembl and Vega. The mutated nucleotide causes a methionine to threonine substitution at amino acid 199 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method.

Protein Function and Prediction

The Pcna gene encodes the 261 amino acid auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand (Uniprot P17918). PCNA is mono-ubiquitinated on Lys164 and this modification is important in the meiotic process and the diversification of the Ig locus through class-switch recombination (CSR) and somatic hypermutation (SHM). PCNA was originally identified by immunofluorescence as a nuclear protein whose appearance correlated with the proliferative state of the cell. Mice lacking PCNA die during early embryogenesis.

Posted On

2011-03-23