Mutagenetix > Incidental Mutation

Incidental Mutation 'R3958:Hcn4'

310809

Institutional Source

Beutler Lab

Gene Symbol

Hcn4

Ensembl Gene

ENSMUSG00000032338

Gene Name

hyperpolarization-activated, cyclic nucleotide-gated K+ 4

Synonyms

MMRRC Submission

040834-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R3958 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

58823412-58863175 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 58844048 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 319 (V319A)

Ref Sequence

ENSEMBL: ENSMUSP00000034889 (fasta)

Gene Model

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

AlphaFold

no structure available at present

Predicted Effect

unknown
Transcript: ENSMUST00000034889
AA Change: V319A

SMART Domains

Protein: ENSMUSP00000034889
Gene: ENSMUSG00000032338
AA Change: V319A

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

0.3284

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.8%
20x: 93.3%

Validation Efficiency

100% (37/37)

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: 33 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Actl9	A	G	17: 33,433,764	K266R	probably benign	Het
Cebpd	T	C	16: 15,887,463	S47P	possibly damaging	Het
Celf4	A	G	18: 25,537,754	M124T	probably benign	Het
Ckap4	C	T	10: 84,528,164	R345H	probably benign	Het
Clasp1	T	C	1: 118,467,881	V183A	probably damaging	Het
Cyp2s1	C	T	7: 25,803,954	R424Q	probably null	Het
Espl1	A	G	15: 102,312,989	I944V	probably damaging	Het
Etl4	A	G	2: 20,340,043	T53A	probably benign	Het
Glyat	A	T	19: 12,639,833	K16N	probably benign	Het
Gm6522	T	C	3: 106,298,804		noncoding transcript	Het
Grin1	G	A	2: 25,313,453	T182M	probably damaging	Het
Hmgcs2	T	C	3: 98,297,477	F317S	possibly damaging	Het
Hoxd8	C	T	2: 74,706,540	Q18*	probably null	Het
Itpr2	C	T	6: 146,425,510	V120I	probably damaging	Het
Kmt2d	G	A	15: 98,855,549	T141M	possibly damaging	Het
Lrp1	A	G	10: 127,571,958	S1821P	probably benign	Het
Neb	T	C	2: 52,263,629	E2428G	probably damaging	Het
Nepn	T	C	10: 52,400,708	V119A	probably benign	Het
Olfr1287	G	T	2: 111,449,885	L248F	possibly damaging	Het
Otogl	T	C	10: 107,821,925	D1048G	probably damaging	Het
Panx1	GTTCTTCT	GTTCT	9: 15,006,171		probably benign	Het
Ppp6r3	A	T	19: 3,496,583	V305D	probably damaging	Het
Prkg2	G	T	5: 98,997,495	T160K	possibly damaging	Het
Prmt8	G	A	6: 127,732,744	T51I	probably benign	Het
Rgl3	T	C	9: 21,975,589		probably benign	Het
Sec23ip	C	G	7: 128,776,850	T796S	probably benign	Het
Selp	T	C	1: 164,126,286	S52P	probably benign	Het
Slc44a2	T	C	9: 21,348,541	I615T	probably damaging	Het
Snap91	T	C	9: 86,838,130	Y118C	probably damaging	Het
Tmem106b	A	T	6: 13,081,588	N165Y	probably damaging	Het
Ucp3	A	G	7: 100,482,739	T266A	probably benign	Het
Ugcg	C	T	4: 59,207,798	P46S	probably benign	Het
Utrn	T	C	10: 12,750,108	I110V	probably damaging	Het

Other mutations in Hcn4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00486:Hcn4	APN	9	58,860,053 (GRCm38)	missense	unknown
IGL00939:Hcn4	APN	9	58,843,927 (GRCm38)	missense	probably benign	0.39
IGL01154:Hcn4	APN	9	58,859,079 (GRCm38)	missense	unknown
IGL01408:Hcn4	APN	9	58,859,886 (GRCm38)	missense	unknown
IGL02658:Hcn4	APN	9	58,859,465 (GRCm38)	missense	unknown
IGL02877:Hcn4	APN	9	58,859,167 (GRCm38)	missense	unknown
IGL03211:Hcn4	APN	9	58,858,151 (GRCm38)	missense	unknown
PIT1430001:Hcn4	UTSW	9	58,859,550 (GRCm38)	missense	unknown
R0049:Hcn4	UTSW	9	58,860,299 (GRCm38)	missense	probably damaging	0.98
R0268:Hcn4	UTSW	9	58,860,162 (GRCm38)	missense	unknown
R0812:Hcn4	UTSW	9	58,823,512 (GRCm38)	start codon destroyed	probably null
R2121:Hcn4	UTSW	9	58,824,058 (GRCm38)	missense	unknown
R3035:Hcn4	UTSW	9	58,823,680 (GRCm38)	missense	unknown
R3715:Hcn4	UTSW	9	58,844,036 (GRCm38)	missense	unknown
R3737:Hcn4	UTSW	9	58,843,889 (GRCm38)	missense	probably benign	0.39
R4035:Hcn4	UTSW	9	58,843,889 (GRCm38)	missense	probably benign	0.39
R4393:Hcn4	UTSW	9	58,844,300 (GRCm38)	missense	unknown
R4418:Hcn4	UTSW	9	58,843,895 (GRCm38)	missense	probably benign	0.39
R4532:Hcn4	UTSW	9	58,857,798 (GRCm38)	missense	unknown
R4765:Hcn4	UTSW	9	58,857,977 (GRCm38)	missense	unknown
R4857:Hcn4	UTSW	9	58,859,570 (GRCm38)	missense	unknown
R4967:Hcn4	UTSW	9	58,859,828 (GRCm38)	missense	unknown
R5068:Hcn4	UTSW	9	58,860,021 (GRCm38)	missense	unknown
R5253:Hcn4	UTSW	9	58,824,275 (GRCm38)	missense	unknown
R5304:Hcn4	UTSW	9	58,843,932 (GRCm38)	missense	probably benign	0.39
R5600:Hcn4	UTSW	9	58,859,293 (GRCm38)	splice site	probably null
R6346:Hcn4	UTSW	9	58,859,044 (GRCm38)	missense	unknown
R6575:Hcn4	UTSW	9	58,824,152 (GRCm38)	missense	unknown
R6622:Hcn4	UTSW	9	58,857,727 (GRCm38)	missense	unknown
R6967:Hcn4	UTSW	9	58,823,945 (GRCm38)	missense	unknown
R7038:Hcn4	UTSW	9	58,823,584 (GRCm38)	missense	unknown
R7054:Hcn4	UTSW	9	58,855,717 (GRCm38)	missense	unknown
R7229:Hcn4	UTSW	9	58,853,399 (GRCm38)	missense	unknown
R7407:Hcn4	UTSW	9	58,859,370 (GRCm38)	missense	unknown
R7448:Hcn4	UTSW	9	58,844,299 (GRCm38)	missense	unknown
R7531:Hcn4	UTSW	9	58,860,137 (GRCm38)	missense	unknown
R7572:Hcn4	UTSW	9	58,823,780 (GRCm38)	missense	unknown
R7680:Hcn4	UTSW	9	58,860,671 (GRCm38)	missense	probably benign	0.08
R7915:Hcn4	UTSW	9	58,823,935 (GRCm38)	missense	unknown
R7956:Hcn4	UTSW	9	58,844,173 (GRCm38)	missense	unknown
R8146:Hcn4	UTSW	9	58,823,744 (GRCm38)	missense	unknown
R8234:Hcn4	UTSW	9	58,844,150 (GRCm38)	missense	unknown
R8421:Hcn4	UTSW	9	58,858,096 (GRCm38)	missense	unknown
R8690:Hcn4	UTSW	9	58,843,910 (GRCm38)	missense	probably benign	0.39
R8855:Hcn4	UTSW	9	58,858,104 (GRCm38)	missense	unknown
R8884:Hcn4	UTSW	9	58,853,422 (GRCm38)	missense	unknown
R9017:Hcn4	UTSW	9	58,824,199 (GRCm38)	missense	unknown
R9151:Hcn4	UTSW	9	58,860,597 (GRCm38)	missense	possibly damaging	0.94
R9331:Hcn4	UTSW	9	58,860,422 (GRCm38)	missense	probably damaging	0.97
R9433:Hcn4	UTSW	9	58,823,939 (GRCm38)	missense	unknown
R9523:Hcn4	UTSW	9	58,859,526 (GRCm38)	missense	unknown
R9541:Hcn4	UTSW	9	58,860,402 (GRCm38)	missense	probably damaging	1.00
R9730:Hcn4	UTSW	9	58,824,210 (GRCm38)	missense	unknown
R9748:Hcn4	UTSW	9	58,823,713 (GRCm38)	missense	unknown
R9753:Hcn4	UTSW	9	58,844,036 (GRCm38)	missense	unknown
R9795:Hcn4	UTSW	9	58,853,479 (GRCm38)	nonsense	probably null
RF011:Hcn4	UTSW	9	58,859,915 (GRCm38)	missense	unknown
X0009:Hcn4	UTSW	9	58,860,759 (GRCm38)	nonsense	probably null
X0057:Hcn4	UTSW	9	58,859,368 (GRCm38)	missense	unknown
Z1176:Hcn4	UTSW	9	58,858,148 (GRCm38)	missense	unknown

Predicted Primers

PCR Primer
(F):5'- TCACTCTCCTGGTGACTGAC -3'
(R):5'- GCTGAGGATCTTAGTGAAACGG -3'

Sequencing Primer
(F):5'- ACTCTGGGCAGATTTTACTGGGAC -3'
(R):5'- TCTTAGTGAAACGGACAATGCGC -3'

Posted On

2015-04-29