Mutagenetix > Incidental Mutation

Incidental Mutation 'R3737:Hcn4'

270175

Institutional Source

Beutler Lab

Gene Symbol

Hcn4

Ensembl Gene

ENSMUSG00000032338

Gene Name

hyperpolarization-activated, cyclic nucleotide-gated K+ 4

Synonyms

MMRRC Submission

040724-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R3737 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

58823412-58863175 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 58843889 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 266 (D266G)

Ref Sequence

ENSEMBL: ENSMUSP00000034889 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000034889]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000034889
AA Change: D266G

PolyPhen 2 Score 0.387 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000034889
Gene: ENSMUSG00000032338
AA Change: D266G

Domain	Start	End	E-Value	Type
low complexity region	27	39	N/A	INTRINSIC
low complexity region	43	59	N/A	INTRINSIC
low complexity region	97	120	N/A	INTRINSIC
low complexity region	150	184	N/A	INTRINSIC
Pfam:Ion_trans_N	218	261	1.2e-23	PFAM
Pfam:Ion_trans	262	525	2.2e-25	PFAM
low complexity region	526	537	N/A	INTRINSIC
Blast:cNMP	538	570	9e-13	BLAST
cNMP	595	708	2.27e-23	SMART
low complexity region	761	771	N/A	INTRINSIC
low complexity region	775	796	N/A	INTRINSIC
low complexity region	808	818	N/A	INTRINSIC
low complexity region	831	856	N/A	INTRINSIC
low complexity region	866	906	N/A	INTRINSIC
low complexity region	915	930	N/A	INTRINSIC
low complexity region	931	956	N/A	INTRINSIC
low complexity region	960	987	N/A	INTRINSIC
low complexity region	991	1004	N/A	INTRINSIC
low complexity region	1021	1036	N/A	INTRINSIC
low complexity region	1045	1073	N/A	INTRINSIC
low complexity region	1123	1140	N/A	INTRINSIC
low complexity region	1154	1164	N/A	INTRINSIC

Meta Mutation Damage Score

0.9556

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.3%
20x: 95.1%

Validation Efficiency

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 hyperpolarization-activated cyclic nucleotide-gated potassium channels. The encoded protein shows slow kinetics of activation and inactivation, and is necessary for the cardiac pacemaking process. This channel may also mediate responses to sour stimuli. Mutations in this gene have been linked to sick sinus syndrome 2, also known as atrial fibrillation with bradyarrhythmia or familial sinus bradycardia. Two pseudogenes have been identified on chromosome 15. [provided by RefSeq, Oct 2008]
PHENOTYPE: Mice homozygous for disruptions in this gene experience embryonic lethality between E9.5 and E11.5. Conditional deletion in cardiac tissue results in severe bradycardia and death. Mice over-expressing the gene exhibit impaired firing rate in ORN, small olfactory bulb and reduced glomeruli. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 50 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Api5	C	T	2: 94,425,613	R243Q	possibly damaging	Het
Arap1	A	T	7: 101,400,277	Y982F	possibly damaging	Het
Bicral	A	T	17: 46,825,910	Y125N	probably damaging	Het
Brd2	A	G	17: 34,117,080	L53S	probably benign	Het
Ccdc88c	G	A	12: 100,930,524	A1389V	possibly damaging	Het
Cdk17	G	A	10: 93,221,644		probably null	Het
Clca3a1	A	G	3: 144,730,721	V867A	probably benign	Het
Dchs1	T	A	7: 105,762,316	D1531V	possibly damaging	Het
Dnah9	G	A	11: 66,156,908	Q29*	probably null	Het
Dopey1	T	C	9: 86,494,433	V240A	probably damaging	Het
Fgfbp1	T	C	5: 43,979,596	Y118C	probably damaging	Het
Gal3st2c	A	G	1: 94,009,328	I332V	possibly damaging	Het
Gprc6a	A	C	10: 51,626,911	N285K	probably benign	Het
Hmcn2	A	T	2: 31,336,612	K200*	probably null	Het
Hmgcr	C	G	13: 96,651,063	L852F	probably damaging	Het
Ifi203	T	A	1: 173,929,474		probably benign	Het
Il1f5	T	C	2: 24,281,203	F101S	probably damaging	Het
Isl2	A	G	9: 55,542,470	S119G	probably benign	Het
Kctd9	G	A	14: 67,734,288	D157N	possibly damaging	Het
Lcorl	A	T	5: 45,734,041	N323K	possibly damaging	Het
Ltbp2	A	T	12: 84,804,474	C836S	probably damaging	Het
Mfsd2b	A	G	12: 4,870,578	S80P	probably damaging	Het
Mon2	A	G	10: 123,013,375	L1340P	probably damaging	Het
Myh9	G	A	15: 77,766,812	R1612C	probably damaging	Het
Nlrp4f	T	C	13: 65,194,007	N608S	probably benign	Het
Nolc1	CAG	CAGTAG	19: 46,081,353		probably benign	Het
Nolc1	GCA	GCAACA	19: 46,081,370		probably benign	Het
Nolc1	C	CAGT	19: 46,081,377		probably benign	Het
Olfr878	G	A	9: 37,918,641		probably benign	Het
Osbpl2	G	A	2: 180,161,560	R475H	probably damaging	Het
Pcm1	T	A	8: 41,261,043	Y215*	probably null	Het
Pde6c	T	A	19: 38,140,224	V212D	probably damaging	Het
Ppl	T	C	16: 5,106,857	T115A	probably benign	Het
Prtg	G	T	9: 72,842,709	E132*	probably null	Het
R3hcc1	C	T	14: 69,697,593	R262Q	probably benign	Het
Serpinb6d	T	A	13: 33,667,680	V140E	probably damaging	Het
Ska3	A	T	14: 57,811,596	M306K	probably benign	Het
Spesp1	T	A	9: 62,273,036	I197L	probably benign	Het
Srsf4	C	T	4: 131,900,102		probably benign	Het
Tprgl	T	C	4: 154,160,128	I137V	probably benign	Het
Ttk	C	A	9: 83,854,837	P450T	possibly damaging	Het
Ube2j1	A	T	4: 33,036,723	M16L	probably benign	Het
Ubr3	G	A	2: 69,971,234		probably null	Het
Usp42	C	T	5: 143,715,439	S943N	probably benign	Het
Usp49	G	A	17: 47,672,318	V83M	probably damaging	Het
Usp6nl	C	A	2: 6,440,917	N568K	probably damaging	Het
Utp20	C	T	10: 88,762,806	V103I	probably benign	Het
Vmn1r55	T	G	7: 5,147,196	D76A	probably damaging	Het
Xrcc6	T	C	15: 82,029,631	Y53H	probably damaging	Het
Zbtb7c	T	G	18: 76,136,940	L33R	probably damaging	Het

Other mutations in Hcn4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00486:Hcn4	APN	9	58860053	missense	unknown
IGL00939:Hcn4	APN	9	58843927	missense	probably benign	0.39
IGL01154:Hcn4	APN	9	58859079	missense	unknown
IGL01408:Hcn4	APN	9	58859886	missense	unknown
IGL02658:Hcn4	APN	9	58859465	missense	unknown
IGL02877:Hcn4	APN	9	58859167	missense	unknown
IGL03211:Hcn4	APN	9	58858151	missense	unknown
PIT1430001:Hcn4	UTSW	9	58859550	missense	unknown
R0049:Hcn4	UTSW	9	58860299	missense	probably damaging	0.98
R0268:Hcn4	UTSW	9	58860162	missense	unknown
R0812:Hcn4	UTSW	9	58823512	start codon destroyed	probably null
R2121:Hcn4	UTSW	9	58824058	missense	unknown
R3035:Hcn4	UTSW	9	58823680	missense	unknown
R3715:Hcn4	UTSW	9	58844036	missense	unknown
R3958:Hcn4	UTSW	9	58844048	missense	unknown
R4035:Hcn4	UTSW	9	58843889	missense	probably benign	0.39
R4393:Hcn4	UTSW	9	58844300	missense	unknown
R4418:Hcn4	UTSW	9	58843895	missense	probably benign	0.39
R4532:Hcn4	UTSW	9	58857798	missense	unknown
R4765:Hcn4	UTSW	9	58857977	missense	unknown
R4857:Hcn4	UTSW	9	58859570	missense	unknown
R4967:Hcn4	UTSW	9	58859828	missense	unknown
R5068:Hcn4	UTSW	9	58860021	missense	unknown
R5253:Hcn4	UTSW	9	58824275	missense	unknown
R5304:Hcn4	UTSW	9	58843932	missense	probably benign	0.39
R5600:Hcn4	UTSW	9	58859293	splice site	probably null
R6346:Hcn4	UTSW	9	58859044	missense	unknown
R6575:Hcn4	UTSW	9	58824152	missense	unknown
R6622:Hcn4	UTSW	9	58857727	missense	unknown
R6967:Hcn4	UTSW	9	58823945	missense	unknown
R7038:Hcn4	UTSW	9	58823584	missense	unknown
R7054:Hcn4	UTSW	9	58855717	missense	unknown
R7229:Hcn4	UTSW	9	58853399	missense	unknown
R7407:Hcn4	UTSW	9	58859370	missense	unknown
R7448:Hcn4	UTSW	9	58844299	missense	unknown
R7531:Hcn4	UTSW	9	58860137	missense	unknown
R7572:Hcn4	UTSW	9	58823780	missense	unknown
R7680:Hcn4	UTSW	9	58860671	missense	probably benign	0.08
R7915:Hcn4	UTSW	9	58823935	missense	unknown
R7956:Hcn4	UTSW	9	58844173	missense	unknown
R8146:Hcn4	UTSW	9	58823744	missense	unknown
R8234:Hcn4	UTSW	9	58844150	missense	unknown
R8421:Hcn4	UTSW	9	58858096	missense	unknown
R8690:Hcn4	UTSW	9	58843910	missense	probably benign	0.39
R8855:Hcn4	UTSW	9	58858104	missense	unknown
R8884:Hcn4	UTSW	9	58853422	missense	unknown
R9017:Hcn4	UTSW	9	58824199	missense	unknown
R9151:Hcn4	UTSW	9	58860597	missense	possibly damaging	0.94
R9331:Hcn4	UTSW	9	58860422	missense	probably damaging	0.97
R9433:Hcn4	UTSW	9	58823939	missense	unknown
R9523:Hcn4	UTSW	9	58859526	missense	unknown
R9541:Hcn4	UTSW	9	58860402	missense	probably damaging	1.00
R9730:Hcn4	UTSW	9	58824210	missense	unknown
R9748:Hcn4	UTSW	9	58823713	missense	unknown
R9753:Hcn4	UTSW	9	58844036	missense	unknown
R9795:Hcn4	UTSW	9	58853479	nonsense	probably null
RF011:Hcn4	UTSW	9	58859915	missense	unknown
X0009:Hcn4	UTSW	9	58860759	nonsense	probably null
X0057:Hcn4	UTSW	9	58859368	missense	unknown
Z1176:Hcn4	UTSW	9	58858148	missense	unknown

Predicted Primers

PCR Primer
(F):5'- GGGAAGCTCTCAGAACACAG -3'
(R):5'- CTCTGCGGGTCAAGGATGATTTC -3'

Sequencing Primer
(F):5'- CACAGACAAAGTGTACCCTGGTG -3'
(R):5'- CAAGGATGATTTCTGTGTTGTCCTCC -3'

Posted On

2015-03-18