Mutagenetix > Incidental Mutation

Incidental Mutation 'R4235:Kdm2a'

321097

Institutional Source

Beutler Lab

Gene Symbol

Kdm2a

Ensembl Gene

ENSMUSG00000054611

Gene Name

lysine (K)-specific demethylase 2A

Synonyms

Gm4560, lalina, Fbl7, Jhdm1a, Cxxc8, Fbxl11, 5530401A10Rik

MMRRC Submission

041052-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.964) question?

Stock #

R4235 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

4314419-4398285 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 4322521 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 932 (I932T)

Ref Sequence

ENSEMBL: ENSMUSP00000076698 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000047898] [ENSMUST00000075856] [ENSMUST00000176653]

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000047898
AA Change: I932T

PolyPhen 2 Score 0.975 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000047683
Gene: ENSMUSG00000054611
AA Change: I932T

Domain	Start	End	E-Value	Type
low complexity region	23	34	N/A	INTRINSIC
low complexity region	127	138	N/A	INTRINSIC
JmjC	148	316	1.52e-34	SMART
low complexity region	416	433	N/A	INTRINSIC
PDB:2YU2\|A	440	517	1e-35	PDB
Pfam:zf-CXXC	563	609	7.5e-16	PFAM
PHD	619	676	3.25e-4	SMART
low complexity region	848	875	N/A	INTRINSIC
FBOX	892	932	1.58e-2	SMART
low complexity region	987	998	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000075856
AA Change: I932T

PolyPhen 2 Score 0.975 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000076698
Gene: ENSMUSG00000054611
AA Change: I932T

Domain	Start	End	E-Value	Type
low complexity region	23	34	N/A	INTRINSIC
low complexity region	127	138	N/A	INTRINSIC
JmjC	148	316	1.52e-34	SMART
low complexity region	416	433	N/A	INTRINSIC
PDB:2YU2\|A	440	517	1e-35	PDB
Pfam:zf-CXXC	563	609	7.5e-16	PFAM
PHD	619	676	3.25e-4	SMART
low complexity region	848	875	N/A	INTRINSIC
FBOX	892	932	1.58e-2	SMART
low complexity region	987	998	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000175978

Predicted Effect

unknown
Transcript: ENSMUST00000176532
AA Change: I9T

Predicted Effect

probably benign
Transcript: ENSMUST00000176653

SMART Domains

Protein: ENSMUSP00000135745
Gene: ENSMUSG00000054611

Domain	Start	End	E-Value	Type
low complexity region	24	35	N/A	INTRINSIC
PDB:2YU2\|A	52	77	4e-7	PDB
Pfam:zf-CXXC	123	169	3e-16	PFAM
PHD	179	236	3.25e-4	SMART

Meta Mutation Damage Score

0.8196

Coding Region Coverage

1x: 99.2%
3x: 98.7%
10x: 97.4%
20x: 95.5%

Validation Efficiency

97% (68/70)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains at least six highly degenerated leucine-rich repeats. This family member plays a role in epigenetic silencing. It nucleates at CpG islands and specifically demethylates both mono- and di-methylated lysine-36 of histone H3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]
PHENOTYPE: Mice homozygous for a null allele show embryonic lethality, severe growth retardation, reduced neuron proliferation, increased neuron apoptosis, impaired neuron differentiation, small hearts, abnormal cardiac looping and, in some cases, incomplete embryonic turning and neural tube closure defects. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 61 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930567H17Rik	C	T	X: 70,394,529	A53T	probably benign	Het
5730596B20Rik	G	T	6: 52,178,961		probably benign	Het
9530053A07Rik	T	A	7: 28,156,648	D1953E	probably damaging	Het
Akap6	T	A	12: 53,139,671	N1289K	probably damaging	Het
Arhgap21	A	G	2: 20,887,137	V161A	probably damaging	Het
Arhgef18	T	C	8: 3,450,317	I541T	possibly damaging	Het
Atp7b	A	G	8: 22,011,023	Y955H	possibly damaging	Het
Bnc2	A	G	4: 84,293,514	V231A	probably damaging	Het
Bod1l	A	G	5: 41,821,455	S839P	probably damaging	Het
Casp8	T	A	1: 58,833,698	H264Q	possibly damaging	Het
Cc2d1b	A	T	4: 108,625,352		probably benign	Het
Cpne6	A	T	14: 55,513,600		probably benign	Het
Ddx1	C	T	12: 13,223,857	V590I	possibly damaging	Het
Dgkd	T	A	1: 87,931,982	L774*	probably null	Het
Fbxl2	T	A	9: 113,989,163	N205I	probably benign	Het
Fkbp15	A	T	4: 62,336,456	I269K	probably benign	Het
Gm13023	G	C	4: 143,794,774	C320S	probably damaging	Het
Gm26678	T	C	3: 54,633,083		noncoding transcript	Het
Has1	G	T	17: 17,850,036	R208S	possibly damaging	Het
Hecw1	C	G	13: 14,317,139	A423P	probably benign	Het
Hspa12b	T	C	2: 131,139,012	V162A	probably benign	Het
Ifi208	T	G	1: 173,682,911	S211A	probably benign	Het
Ighv6-3	T	C	12: 114,391,874	E65G	probably damaging	Het
Igkv9-120	A	T	6: 68,050,333	D77V	probably benign	Het
Impg1	A	G	9: 80,345,329	L523P	probably damaging	Het
Ip6k2	G	A	9: 108,805,648	R319Q	probably benign	Het
Krt17	T	C	11: 100,257,868	T279A	possibly damaging	Het
Lamp1	T	C	8: 13,167,192	V67A	possibly damaging	Het
Limk1	T	C	5: 134,670,478	I142V	probably benign	Het
Mamdc2	T	C	19: 23,374,017	N182D	possibly damaging	Het
Mcpt1	G	A	14: 56,018,560		probably null	Het
Med12l	T	G	3: 59,257,223		probably null	Het
Mfsd10	G	T	5: 34,635,625	T44N	probably damaging	Het
Mrps27	T	C	13: 99,405,041	S218P	probably damaging	Het
Mrps30	T	C	13: 118,386,840	D132G	probably damaging	Het
Neil2	A	C	14: 63,191,841	M1R	probably null	Het
Nelfcd	T	C	2: 174,427,048	F587L	probably damaging	Het
Nfil3	T	C	13: 52,968,799	D23G	probably benign	Het
Nit2	T	C	16: 57,157,160	K169R	probably benign	Het
Nxt1	T	C	2: 148,675,347	S3P	probably benign	Het
Ogt	A	G	X: 101,667,525	N434D	probably damaging	Het
Olfr679	T	A	7: 105,085,787	S24T	possibly damaging	Het
Pcdhga5	A	G	18: 37,695,948	D483G	possibly damaging	Het
Ralgapa1	C	T	12: 55,640,644	R2019Q	probably damaging	Het
Rsl1	T	C	13: 67,177,162		probably null	Het
Sobp	G	A	10: 43,022,900	H230Y	probably damaging	Het
Sptan1	A	G	2: 30,026,588	E2096G	probably damaging	Het
Tie1	G	T	4: 118,478,405	S797*	probably null	Het
Tmem266	T	C	9: 55,418,107	I186T	probably damaging	Het
Tmem38b	T	C	4: 53,840,710	C66R	probably damaging	Het
Tnfaip6	T	C	2: 52,050,864	F139S	probably damaging	Het
Tnrc6a	T	C	7: 123,171,680	S898P	probably benign	Het
Trim24	A	G	6: 37,964,740	D911G	probably damaging	Het
Tyw5	T	C	1: 57,388,488		probably benign	Het
Ubr3	C	T	2: 70,016,385	Q1651*	probably null	Het
Unc13c	T	A	9: 73,530,952	I1943F	possibly damaging	Het
Usp47	T	A	7: 112,110,048	S1334T	probably damaging	Het
Vmn1r215	T	A	13: 23,075,931	V47E	probably benign	Het
Vmn1r224	T	A	17: 20,419,362	M67K	possibly damaging	Het
Wdfy3	T	A	5: 101,922,634		probably null	Het
Zfc3h1	T	C	10: 115,418,799	Y1433H	probably benign	Het

Other mutations in Kdm2a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00334:Kdm2a	APN	19	4356898	missense	possibly damaging	0.94
IGL00679:Kdm2a	APN	19	4326841	missense	probably damaging	1.00
IGL01104:Kdm2a	APN	19	4356738	splice site	probably benign
IGL01161:Kdm2a	APN	19	4319251	missense	probably benign	0.04
IGL01433:Kdm2a	APN	19	4342860	missense	possibly damaging	0.83
IGL01456:Kdm2a	APN	19	4351755	missense	probably damaging	1.00
IGL01467:Kdm2a	APN	19	4324407	missense	probably damaging	0.99
IGL01517:Kdm2a	APN	19	4362061	splice site	probably benign
IGL01528:Kdm2a	APN	19	4343055	missense	probably benign	0.18
IGL02504:Kdm2a	APN	19	4356771	missense	possibly damaging	0.92
IGL02895:Kdm2a	APN	19	4362902	missense	probably damaging	1.00
IGL03109:Kdm2a	APN	19	4329107	missense	probably benign	0.04
IGL03171:Kdm2a	APN	19	4356764	missense	probably damaging	1.00
IGL03256:Kdm2a	APN	19	4345510	unclassified	probably benign
BB009:Kdm2a	UTSW	19	4319156	missense	probably damaging	0.98
BB019:Kdm2a	UTSW	19	4319156	missense	probably damaging	0.98
P0027:Kdm2a	UTSW	19	4343245	splice site	probably benign
PIT4382001:Kdm2a	UTSW	19	4343173	missense	probably benign
R0220:Kdm2a	UTSW	19	4324919	missense	possibly damaging	0.85
R0961:Kdm2a	UTSW	19	4329191	missense	probably benign	0.07
R1662:Kdm2a	UTSW	19	4328212	missense	probably damaging	1.00
R2023:Kdm2a	UTSW	19	4322464	missense	probably damaging	0.98
R2191:Kdm2a	UTSW	19	4356931	splice site	probably null
R2207:Kdm2a	UTSW	19	4362870	missense	probably damaging	1.00
R2351:Kdm2a	UTSW	19	4329126	missense	probably benign	0.02
R2406:Kdm2a	UTSW	19	4322518	missense	probably damaging	1.00
R2882:Kdm2a	UTSW	19	4331184	critical splice donor site	probably null
R3788:Kdm2a	UTSW	19	4351805	missense	probably damaging	0.99
R3792:Kdm2a	UTSW	19	4324512	missense	possibly damaging	0.91
R3950:Kdm2a	UTSW	19	4343232	missense	possibly damaging	0.89
R4377:Kdm2a	UTSW	19	4329054	missense	probably benign	0.01
R4466:Kdm2a	UTSW	19	4320300	missense	probably damaging	0.99
R4766:Kdm2a	UTSW	19	4324507	unclassified	probably benign
R4824:Kdm2a	UTSW	19	4362787	missense	probably damaging	1.00
R4838:Kdm2a	UTSW	19	4325026	missense	probably benign	0.41
R5283:Kdm2a	UTSW	19	4331269	missense	probably benign	0.00
R6366:Kdm2a	UTSW	19	4324932	missense	probably benign	0.15
R6368:Kdm2a	UTSW	19	4350317	missense	probably damaging	1.00
R6522:Kdm2a	UTSW	19	4324826	missense	possibly damaging	0.49
R6716:Kdm2a	UTSW	19	4329102	missense	probably damaging	1.00
R6757:Kdm2a	UTSW	19	4319243	missense	probably damaging	0.98
R6912:Kdm2a	UTSW	19	4322501	missense	probably benign	0.06
R6996:Kdm2a	UTSW	19	4345641	missense	probably benign	0.16
R7090:Kdm2a	UTSW	19	4319141	missense	probably damaging	1.00
R7497:Kdm2a	UTSW	19	4324376	missense	probably damaging	1.00
R7542:Kdm2a	UTSW	19	4333830	start gained	probably benign
R7932:Kdm2a	UTSW	19	4319156	missense	probably damaging	0.98
R8199:Kdm2a	UTSW	19	4389026	missense	unknown
R8263:Kdm2a	UTSW	19	4324364	missense	possibly damaging	0.88
R8446:Kdm2a	UTSW	19	4356888	nonsense	probably null
R9158:Kdm2a	UTSW	19	4324687	missense	possibly damaging	0.49
R9303:Kdm2a	UTSW	19	4345578	missense	probably benign	0.01
R9314:Kdm2a	UTSW	19	4322482	missense	probably damaging	1.00
R9351:Kdm2a	UTSW	19	4343113	missense
R9353:Kdm2a	UTSW	19	4343113	missense
R9411:Kdm2a	UTSW	19	4362807	missense	probably damaging	0.99
R9456:Kdm2a	UTSW	19	4343113	missense
R9616:Kdm2a	UTSW	19	4320280	missense	probably damaging	0.99
R9625:Kdm2a	UTSW	19	4343113	missense
RF046:Kdm2a	UTSW	19	4324507	unclassified	probably benign
X0028:Kdm2a	UTSW	19	4320271	missense	possibly damaging	0.77
X0028:Kdm2a	UTSW	19	4348746	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TCCCCAAACTGCATTGCATC -3'
(R):5'- GCCTGACTCTGAGGTAGAAAATG -3'

Sequencing Primer
(F):5'- GCATTGCATCAGTTCTAAGCAGC -3'
(R):5'- CTGAGGTAGAAAATGACAGAGATTTC -3'

Posted On

2015-06-12