Incidental Mutation 'R4035:Hcn4'
ID 313676
Institutional Source Beutler Lab
Gene Symbol Hcn4
Ensembl Gene ENSMUSG00000032338
Gene Name hyperpolarization-activated, cyclic nucleotide-gated K+ 4
Synonyms
MMRRC Submission 041613-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4035 (G1)
Quality Score 225
Status Validated
Chromosome 9
Chromosomal Location 58730695-58770458 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 58751172 bp (GRCm39)
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

DomainStartEndE-ValueType
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 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.5%
  • 10x: 97.1%
  • 20x: 94.5%
Validation Efficiency 100% (51/51)
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: 52 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700013D24Rik A G 6: 124,333,879 (GRCm39) F34L probably benign Het
Abcb8 A G 5: 24,605,619 (GRCm39) S168G probably benign Het
Ano5 A G 7: 51,216,233 (GRCm39) probably benign Het
Api5 C T 2: 94,255,958 (GRCm39) R243Q possibly damaging Het
Bhlhe41 A G 6: 145,808,754 (GRCm39) S353P probably benign Het
Ccdc88c G A 12: 100,896,783 (GRCm39) A1389V possibly damaging Het
Cep350 T C 1: 155,835,541 (GRCm39) T52A probably benign Het
Coro2b A G 9: 62,333,071 (GRCm39) probably benign Het
Ctcf A T 8: 106,390,789 (GRCm39) E132V possibly damaging Het
Cwf19l2 A T 9: 3,456,803 (GRCm39) H712L probably benign Het
Cxcl2 A T 5: 91,052,272 (GRCm39) Q87L possibly damaging Het
Dop1a T C 9: 86,376,486 (GRCm39) V240A probably damaging Het
Etfdh C T 3: 79,521,018 (GRCm39) V294I probably benign Het
Fnip2 C T 3: 79,386,808 (GRCm39) V973I probably benign Het
Fyco1 T C 9: 123,630,348 (GRCm39) T1286A probably benign Het
Gbp10 T A 5: 105,372,324 (GRCm39) E145D possibly damaging Het
Gsdme A T 6: 50,206,428 (GRCm39) N138K possibly damaging Het
Henmt1 T C 3: 108,866,001 (GRCm39) V199A probably damaging Het
Hmcn2 A T 2: 31,226,624 (GRCm39) K200* probably null Het
Hmgcr C G 13: 96,787,571 (GRCm39) L852F probably damaging Het
Ifi203 T A 1: 173,757,040 (GRCm39) probably benign Het
Isl2 A G 9: 55,449,754 (GRCm39) S119G probably benign Het
Krba1 A G 6: 48,388,614 (GRCm39) N538D probably damaging Het
Lcorl A T 5: 45,891,383 (GRCm39) N323K possibly damaging Het
Mfsd2b A G 12: 4,920,578 (GRCm39) S80P probably damaging Het
Ndst4 C T 3: 125,232,385 (GRCm39) T318M probably damaging Het
Nlrp4f T C 13: 65,341,821 (GRCm39) N608S probably benign Het
Nolc1 GCA GCACCA 19: 46,069,797 (GRCm39) probably benign Het
Or6d12 A G 6: 116,493,590 (GRCm39) N284S possibly damaging Het
Or8b4 G A 9: 37,829,937 (GRCm39) probably benign Het
Osbpl2 G A 2: 179,803,353 (GRCm39) R475H probably damaging Het
Ppfibp1 A G 6: 146,898,334 (GRCm39) K97E probably damaging Het
Pramel26 T A 4: 143,537,026 (GRCm39) D435V probably benign Het
Prpsap1 A T 11: 116,363,834 (GRCm39) M263K probably benign Het
Prtg G T 9: 72,749,991 (GRCm39) E132* probably null Het
Ptch1 T G 13: 63,672,773 (GRCm39) E944A probably benign Het
Rttn T C 18: 89,013,777 (GRCm39) V482A probably benign Het
Samsn1 A G 16: 75,706,073 (GRCm39) M1T probably null Het
Scel A G 14: 103,767,440 (GRCm39) N33S probably damaging Het
Sema4g A T 19: 44,989,853 (GRCm39) Y644F probably damaging Het
Slc39a10 G A 1: 46,851,234 (GRCm39) T752M probably damaging Het
Snx27 T C 3: 94,431,551 (GRCm39) D281G probably damaging Het
Spesp1 T A 9: 62,180,318 (GRCm39) I197L probably benign Het
Srsf4 C T 4: 131,627,413 (GRCm39) probably benign Het
Tpgs1 A G 10: 79,505,199 (GRCm39) probably null Het
Trpc2 G A 7: 101,733,711 (GRCm39) S220N probably damaging Het
Ttk C A 9: 83,736,890 (GRCm39) P450T possibly damaging Het
Ttn T G 2: 76,740,165 (GRCm39) Q3458P probably benign Het
Ube2z A G 11: 95,951,893 (GRCm39) F152L probably damaging Het
Utp20 C T 10: 88,598,668 (GRCm39) V103I probably benign Het
Zfa-ps T A 10: 52,420,636 (GRCm39) noncoding transcript Het
Zfp267 T G 3: 36,218,989 (GRCm39) H337Q possibly damaging Het
Other mutations in Hcn4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00486:Hcn4 APN 9 58,767,336 (GRCm39) missense unknown
IGL00939:Hcn4 APN 9 58,751,210 (GRCm39) missense probably benign 0.39
IGL01154:Hcn4 APN 9 58,766,362 (GRCm39) missense unknown
IGL01408:Hcn4 APN 9 58,767,169 (GRCm39) missense unknown
IGL02658:Hcn4 APN 9 58,766,748 (GRCm39) missense unknown
IGL02877:Hcn4 APN 9 58,766,450 (GRCm39) missense unknown
IGL03211:Hcn4 APN 9 58,765,434 (GRCm39) missense unknown
PIT1430001:Hcn4 UTSW 9 58,766,833 (GRCm39) missense unknown
R0049:Hcn4 UTSW 9 58,767,582 (GRCm39) missense probably damaging 0.98
R0268:Hcn4 UTSW 9 58,767,445 (GRCm39) missense unknown
R0812:Hcn4 UTSW 9 58,730,795 (GRCm39) start codon destroyed probably null
R2121:Hcn4 UTSW 9 58,731,341 (GRCm39) missense unknown
R3035:Hcn4 UTSW 9 58,730,963 (GRCm39) missense unknown
R3715:Hcn4 UTSW 9 58,751,319 (GRCm39) missense unknown
R3737:Hcn4 UTSW 9 58,751,172 (GRCm39) missense probably benign 0.39
R3958:Hcn4 UTSW 9 58,751,331 (GRCm39) missense unknown
R4393:Hcn4 UTSW 9 58,751,583 (GRCm39) missense unknown
R4418:Hcn4 UTSW 9 58,751,178 (GRCm39) missense probably benign 0.39
R4532:Hcn4 UTSW 9 58,765,081 (GRCm39) missense unknown
R4765:Hcn4 UTSW 9 58,765,260 (GRCm39) missense unknown
R4857:Hcn4 UTSW 9 58,766,853 (GRCm39) missense unknown
R4967:Hcn4 UTSW 9 58,767,111 (GRCm39) missense unknown
R5068:Hcn4 UTSW 9 58,767,304 (GRCm39) missense unknown
R5253:Hcn4 UTSW 9 58,731,558 (GRCm39) missense unknown
R5304:Hcn4 UTSW 9 58,751,215 (GRCm39) missense probably benign 0.39
R5600:Hcn4 UTSW 9 58,766,576 (GRCm39) splice site probably null
R6346:Hcn4 UTSW 9 58,766,327 (GRCm39) missense unknown
R6575:Hcn4 UTSW 9 58,731,435 (GRCm39) missense unknown
R6622:Hcn4 UTSW 9 58,765,010 (GRCm39) missense unknown
R6967:Hcn4 UTSW 9 58,731,228 (GRCm39) missense unknown
R7038:Hcn4 UTSW 9 58,730,867 (GRCm39) missense unknown
R7054:Hcn4 UTSW 9 58,763,000 (GRCm39) missense unknown
R7229:Hcn4 UTSW 9 58,760,682 (GRCm39) missense unknown
R7407:Hcn4 UTSW 9 58,766,653 (GRCm39) missense unknown
R7448:Hcn4 UTSW 9 58,751,582 (GRCm39) missense unknown
R7531:Hcn4 UTSW 9 58,767,420 (GRCm39) missense unknown
R7572:Hcn4 UTSW 9 58,731,063 (GRCm39) missense unknown
R7680:Hcn4 UTSW 9 58,767,954 (GRCm39) missense probably benign 0.08
R7915:Hcn4 UTSW 9 58,731,218 (GRCm39) missense unknown
R7956:Hcn4 UTSW 9 58,751,456 (GRCm39) missense unknown
R8146:Hcn4 UTSW 9 58,731,027 (GRCm39) missense unknown
R8234:Hcn4 UTSW 9 58,751,433 (GRCm39) missense unknown
R8421:Hcn4 UTSW 9 58,765,379 (GRCm39) missense unknown
R8690:Hcn4 UTSW 9 58,751,193 (GRCm39) missense probably benign 0.39
R8855:Hcn4 UTSW 9 58,765,387 (GRCm39) missense unknown
R8884:Hcn4 UTSW 9 58,760,705 (GRCm39) missense unknown
R9017:Hcn4 UTSW 9 58,731,482 (GRCm39) missense unknown
R9151:Hcn4 UTSW 9 58,767,880 (GRCm39) missense possibly damaging 0.94
R9331:Hcn4 UTSW 9 58,767,705 (GRCm39) missense probably damaging 0.97
R9433:Hcn4 UTSW 9 58,731,222 (GRCm39) missense unknown
R9523:Hcn4 UTSW 9 58,766,809 (GRCm39) missense unknown
R9541:Hcn4 UTSW 9 58,767,685 (GRCm39) missense probably damaging 1.00
R9730:Hcn4 UTSW 9 58,731,493 (GRCm39) missense unknown
R9748:Hcn4 UTSW 9 58,730,996 (GRCm39) missense unknown
R9753:Hcn4 UTSW 9 58,751,319 (GRCm39) missense unknown
R9795:Hcn4 UTSW 9 58,760,762 (GRCm39) nonsense probably null
RF011:Hcn4 UTSW 9 58,767,198 (GRCm39) missense unknown
X0009:Hcn4 UTSW 9 58,768,042 (GRCm39) nonsense probably null
X0057:Hcn4 UTSW 9 58,766,651 (GRCm39) missense unknown
Z1176:Hcn4 UTSW 9 58,765,431 (GRCm39) missense unknown
Predicted Primers PCR Primer
(F):5'- TGGGAAGCTCTCAGAACACAG -3'
(R):5'- TGCGGGTCAAGGATGATTTC -3'

Sequencing Primer
(F):5'- CACAGACAAAGTGTACCCTGGTG -3'
(R):5'- CAAGGATGATTTCTGTGTTGTCCTCC -3'
Posted On 2015-04-30