Incidental Mutation 'R9325:Slc4a4'
ID 706449
Institutional Source Beutler Lab
Gene Symbol Slc4a4
Ensembl Gene ENSMUSG00000060961
Gene Name solute carrier family 4 (anion exchanger), member 4
Synonyms NBC, NBC1
MMRRC Submission
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R9325 (G1)
Quality Score 214.009
Status Validated
Chromosome 5
Chromosomal Location 89034345-89387512 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 89376756 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glutamic Acid at position 994 (D994E)
Ref Sequence ENSEMBL: ENSMUSP00000108844 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000113218] [ENSMUST00000130041] [ENSMUST00000148750] [ENSMUST00000156238]
AlphaFold O88343
Predicted Effect probably damaging
Transcript: ENSMUST00000113218
AA Change: D994E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000108844
Gene: ENSMUSG00000060961
AA Change: D994E

DomainStartEndE-ValueType
low complexity region 40 59 N/A INTRINSIC
low complexity region 76 87 N/A INTRINSIC
Pfam:Band_3_cyto 137 379 1.1e-100 PFAM
low complexity region 408 423 N/A INTRINSIC
Pfam:HCO3_cotransp 426 947 3e-246 PFAM
transmembrane domain 953 975 N/A INTRINSIC
low complexity region 999 1015 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000130041
AA Change: D959E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000118413
Gene: ENSMUSG00000060961
AA Change: D959E

DomainStartEndE-ValueType
Pfam:Band_3_cyto 93 344 1.5e-101 PFAM
low complexity region 373 388 N/A INTRINSIC
Pfam:HCO3_cotransp 391 912 2.7e-246 PFAM
transmembrane domain 918 940 N/A INTRINSIC
low complexity region 964 980 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000148750
AA Change: D1003E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000119325
Gene: ENSMUSG00000060961
AA Change: D1003E

DomainStartEndE-ValueType
low complexity region 40 59 N/A INTRINSIC
low complexity region 76 87 N/A INTRINSIC
Pfam:Band_3_cyto 137 388 3.7e-101 PFAM
low complexity region 417 432 N/A INTRINSIC
Pfam:HCO3_cotransp 435 956 7.3e-246 PFAM
transmembrane domain 962 984 N/A INTRINSIC
low complexity region 1008 1024 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000156238
AA Change: D1003E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000121744
Gene: ENSMUSG00000060961
AA Change: D1003E

DomainStartEndE-ValueType
low complexity region 40 59 N/A INTRINSIC
low complexity region 76 87 N/A INTRINSIC
Pfam:Band_3_cyto 137 388 4.6e-101 PFAM
low complexity region 417 432 N/A INTRINSIC
Pfam:HCO3_cotransp 436 956 4.1e-231 PFAM
transmembrane domain 962 984 N/A INTRINSIC
low complexity region 1008 1024 N/A INTRINSIC
Meta Mutation Damage Score 0.6683 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.1%
Validation Efficiency 98% (59/60)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a sodium bicarbonate cotransporter (NBC) involved in the regulation of bicarbonate secretion and absorption and intracellular pH. Mutations in this gene are associated with proximal renal tubular acidosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]
PHENOTYPE: Mice homozygous for a null allele exhibit smaller birth size, growth retardation, postnatal lethality, bowel obstructions, altered blood chemistry, acidosis, spleen defects and defects in ion homeostasis. Heterozygotes have decreased levels of circulating bicarbonate. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 62 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A2m A G 6: 121,646,578 (GRCm39) D1076G possibly damaging Het
Aadacl2fm1 T A 3: 59,843,862 (GRCm39) N185K probably benign Het
Adamts9 T C 6: 92,849,279 (GRCm39) D1060G probably benign Het
Ahnak T A 19: 8,991,257 (GRCm39) D4180E probably benign Het
Ank2 A C 3: 126,775,504 (GRCm39) F42V probably damaging Het
Ankib1 A G 5: 3,822,523 (GRCm39) I61T possibly damaging Het
Arhgap9 T C 10: 127,161,722 (GRCm39) S238P probably damaging Het
Bpifa3 A T 2: 153,975,600 (GRCm39) I57F probably damaging Het
Cdh17 A G 4: 11,810,319 (GRCm39) Y670C probably damaging Het
Ceacam20 C A 7: 19,720,607 (GRCm39) R515S probably benign Het
Cers5 A T 15: 99,637,338 (GRCm39) V274E probably damaging Het
Clip1 T C 5: 123,751,186 (GRCm39) D865G Het
Cnih3 G A 1: 181,181,072 (GRCm39) probably null Het
Coro2b G T 9: 62,396,609 (GRCm39) H44N probably benign Het
Cuta A G 17: 27,158,289 (GRCm39) probably null Het
Dchs1 T C 7: 105,415,402 (GRCm39) I625V possibly damaging Het
Ddx4 A T 13: 112,736,441 (GRCm39) F643Y probably damaging Het
Dlc1 A T 8: 37,038,518 (GRCm39) V1020E possibly damaging Het
Dnah1 G T 14: 30,998,160 (GRCm39) T2559K possibly damaging Het
Eng C T 2: 32,561,445 (GRCm39) A152V probably damaging Het
F7 G T 8: 13,083,430 (GRCm39) R190L probably benign Het
Fcgr4 T C 1: 170,847,711 (GRCm39) V103A probably damaging Het
Fer1l4 C T 2: 155,877,934 (GRCm39) V1005I probably damaging Het
Fmod A T 1: 133,968,371 (GRCm39) H137L probably damaging Het
Fndc7 T C 3: 108,790,834 (GRCm39) D64G possibly damaging Het
Gucy2c A T 6: 136,743,992 (GRCm39) C202* probably null Het
Hspg2 C T 4: 137,265,552 (GRCm39) R1783W probably damaging Het
Hyal6 T A 6: 24,743,455 (GRCm39) S384T probably damaging Het
Igsf21 T A 4: 139,794,466 (GRCm39) I136F probably damaging Het
Isl1 A G 13: 116,436,105 (GRCm39) S321P probably damaging Het
Kif5c A G 2: 49,639,378 (GRCm39) K813R probably benign Het
Klk7 A G 7: 43,461,437 (GRCm39) E18G possibly damaging Het
Lox T C 18: 52,661,400 (GRCm39) M225V probably benign Het
Lrrfip2 T A 9: 110,990,429 (GRCm39) M50K possibly damaging Het
Lrrn2 A T 1: 132,865,241 (GRCm39) Q102L probably damaging Het
Mcm3 T C 1: 20,875,562 (GRCm39) R692G probably benign Het
Mmp14 T C 14: 54,676,248 (GRCm39) V326A probably damaging Het
Muc2 G A 7: 141,298,559 (GRCm39) M70I Het
Nefl T C 14: 68,322,460 (GRCm39) probably null Het
Nlrp4e C G 7: 23,020,755 (GRCm39) A414G probably benign Het
Nup188 T A 2: 30,212,271 (GRCm39) L586Q probably damaging Het
Or10ag58 G A 2: 87,265,290 (GRCm39) G153D possibly damaging Het
Or8c13 T C 9: 38,091,327 (GRCm39) D264G probably benign Het
Pik3c2a A T 7: 115,990,558 (GRCm39) D467E probably damaging Het
Polr2g T A 19: 8,774,669 (GRCm39) K71N probably benign Het
Pramel31 A G 4: 144,089,093 (GRCm39) H137R probably benign Het
Prkci A G 3: 31,085,333 (GRCm39) K184R probably damaging Het
Prr15 G A 6: 54,306,137 (GRCm39) probably benign Het
Rin2 T A 2: 145,727,819 (GRCm39) N896K probably benign Het
Ryr3 T C 2: 112,479,640 (GRCm39) E4414G probably damaging Het
Slc6a4 C A 11: 76,909,999 (GRCm39) P418Q probably benign Het
Smarcc2 T A 10: 128,324,076 (GRCm39) M1138K unknown Het
Snph C T 2: 151,436,208 (GRCm39) R240Q probably damaging Het
Stox2 T A 8: 47,647,095 (GRCm39) T122S probably benign Het
Tmem131l T C 3: 83,817,768 (GRCm39) D1244G probably benign Het
Tmem168 T C 6: 13,583,253 (GRCm39) I543V probably benign Het
Tyw1 T C 5: 130,291,762 (GRCm39) S77P probably damaging Het
Usp36 T G 11: 118,160,031 (GRCm39) D471A possibly damaging Het
Vmn2r102 A G 17: 19,897,558 (GRCm39) Y191C probably damaging Het
Vmn2r104 T C 17: 20,268,433 (GRCm39) Q12R possibly damaging Het
Zfp820 A T 17: 22,038,380 (GRCm39) I316N probably damaging Het
Zscan4-ps3 T C 7: 11,344,227 (GRCm39) F62L probably damaging Het
Other mutations in Slc4a4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00827:Slc4a4 APN 5 89,327,545 (GRCm39) missense probably benign 0.01
IGL00976:Slc4a4 APN 5 89,102,657 (GRCm39) missense probably damaging 1.00
IGL01074:Slc4a4 APN 5 89,327,633 (GRCm39) missense probably damaging 1.00
IGL01120:Slc4a4 APN 5 89,280,238 (GRCm39) missense probably damaging 1.00
IGL01284:Slc4a4 APN 5 89,277,532 (GRCm39) missense probably benign 0.22
IGL01375:Slc4a4 APN 5 89,327,593 (GRCm39) missense probably damaging 1.00
IGL01399:Slc4a4 APN 5 89,376,794 (GRCm39) missense probably damaging 1.00
IGL01487:Slc4a4 APN 5 89,376,715 (GRCm39) missense probably benign 0.19
IGL02501:Slc4a4 APN 5 89,277,508 (GRCm39) missense probably benign 0.13
IGL03104:Slc4a4 APN 5 89,297,231 (GRCm39) missense probably damaging 1.00
IGL03157:Slc4a4 APN 5 89,304,372 (GRCm39) missense probably damaging 0.99
IGL03205:Slc4a4 APN 5 89,297,189 (GRCm39) missense probably benign 0.00
IGL03356:Slc4a4 APN 5 89,270,342 (GRCm39) missense probably benign 0.00
IGL03372:Slc4a4 APN 5 89,304,285 (GRCm39) missense probably damaging 1.00
IGL03382:Slc4a4 APN 5 89,376,695 (GRCm39) missense probably damaging 1.00
camera UTSW 5 89,280,366 (GRCm39) missense probably damaging 1.00
pixels UTSW 5 89,270,262 (GRCm39) missense probably damaging 0.99
Shutter UTSW 5 89,373,807 (GRCm39) missense probably damaging 1.00
Tetrapod UTSW 5 89,376,831 (GRCm39) missense probably damaging 1.00
Therapod UTSW 5 89,283,581 (GRCm39) missense probably damaging 1.00
tripod UTSW 5 89,297,192 (GRCm39) missense possibly damaging 0.52
BB008:Slc4a4 UTSW 5 89,318,640 (GRCm39) missense probably benign 0.00
BB018:Slc4a4 UTSW 5 89,318,640 (GRCm39) missense probably benign 0.00
PIT4515001:Slc4a4 UTSW 5 89,281,112 (GRCm39) missense probably damaging 1.00
PIT4544001:Slc4a4 UTSW 5 89,186,402 (GRCm39) missense probably damaging 1.00
R0007:Slc4a4 UTSW 5 89,186,437 (GRCm39) missense probably damaging 1.00
R0052:Slc4a4 UTSW 5 89,304,195 (GRCm39) missense possibly damaging 0.71
R0052:Slc4a4 UTSW 5 89,304,195 (GRCm39) missense possibly damaging 0.71
R0054:Slc4a4 UTSW 5 89,304,195 (GRCm39) missense possibly damaging 0.71
R0055:Slc4a4 UTSW 5 89,304,195 (GRCm39) missense possibly damaging 0.71
R0230:Slc4a4 UTSW 5 89,304,195 (GRCm39) missense possibly damaging 0.71
R0234:Slc4a4 UTSW 5 89,304,195 (GRCm39) missense possibly damaging 0.71
R0234:Slc4a4 UTSW 5 89,304,195 (GRCm39) missense possibly damaging 0.71
R0632:Slc4a4 UTSW 5 89,277,500 (GRCm39) missense probably damaging 1.00
R1199:Slc4a4 UTSW 5 89,363,653 (GRCm39) critical splice donor site probably null
R1597:Slc4a4 UTSW 5 89,283,587 (GRCm39) missense probably benign 0.01
R1783:Slc4a4 UTSW 5 89,280,273 (GRCm39) missense probably damaging 1.00
R1813:Slc4a4 UTSW 5 89,194,167 (GRCm39) missense probably damaging 0.98
R1896:Slc4a4 UTSW 5 89,194,167 (GRCm39) missense probably damaging 0.98
R2000:Slc4a4 UTSW 5 89,176,206 (GRCm39) missense probably damaging 1.00
R2139:Slc4a4 UTSW 5 89,194,123 (GRCm39) missense probably damaging 1.00
R2163:Slc4a4 UTSW 5 89,362,435 (GRCm39) missense probably damaging 1.00
R2513:Slc4a4 UTSW 5 89,304,257 (GRCm39) missense probably benign 0.00
R2873:Slc4a4 UTSW 5 89,283,623 (GRCm39) missense probably damaging 1.00
R2995:Slc4a4 UTSW 5 89,082,673 (GRCm39) missense probably damaging 1.00
R3054:Slc4a4 UTSW 5 89,373,807 (GRCm39) missense probably damaging 1.00
R3055:Slc4a4 UTSW 5 89,373,807 (GRCm39) missense probably damaging 1.00
R3055:Slc4a4 UTSW 5 89,280,366 (GRCm39) missense probably damaging 1.00
R3056:Slc4a4 UTSW 5 89,373,807 (GRCm39) missense probably damaging 1.00
R3617:Slc4a4 UTSW 5 89,382,663 (GRCm39) missense probably benign 0.00
R3856:Slc4a4 UTSW 5 89,380,698 (GRCm39) missense probably benign 0.00
R3863:Slc4a4 UTSW 5 89,283,507 (GRCm39) missense possibly damaging 0.95
R3896:Slc4a4 UTSW 5 89,345,625 (GRCm39) splice site probably benign
R4007:Slc4a4 UTSW 5 89,362,452 (GRCm39) missense probably damaging 1.00
R4616:Slc4a4 UTSW 5 89,186,420 (GRCm39) missense probably damaging 1.00
R4740:Slc4a4 UTSW 5 89,373,753 (GRCm39) missense probably damaging 1.00
R5009:Slc4a4 UTSW 5 89,297,157 (GRCm39) critical splice acceptor site probably null
R5119:Slc4a4 UTSW 5 89,102,721 (GRCm39) missense probably null 0.97
R5228:Slc4a4 UTSW 5 89,304,384 (GRCm39) missense possibly damaging 0.50
R5394:Slc4a4 UTSW 5 89,345,623 (GRCm39) critical splice donor site probably null
R5396:Slc4a4 UTSW 5 89,194,076 (GRCm39) missense probably benign 0.00
R5662:Slc4a4 UTSW 5 89,176,103 (GRCm39) missense probably damaging 0.96
R5664:Slc4a4 UTSW 5 89,176,103 (GRCm39) missense probably damaging 0.96
R6021:Slc4a4 UTSW 5 89,188,261 (GRCm39) intron probably benign
R6088:Slc4a4 UTSW 5 89,345,563 (GRCm39) missense probably benign 0.12
R6337:Slc4a4 UTSW 5 89,194,231 (GRCm39) missense probably benign 0.21
R6416:Slc4a4 UTSW 5 89,327,588 (GRCm39) missense probably benign 0.26
R6452:Slc4a4 UTSW 5 89,376,839 (GRCm39) missense probably benign 0.05
R6524:Slc4a4 UTSW 5 89,380,623 (GRCm39) missense probably benign 0.01
R6566:Slc4a4 UTSW 5 89,297,192 (GRCm39) missense possibly damaging 0.52
R6727:Slc4a4 UTSW 5 89,318,624 (GRCm39) missense probably benign 0.00
R6844:Slc4a4 UTSW 5 89,376,831 (GRCm39) missense probably damaging 1.00
R6970:Slc4a4 UTSW 5 89,327,690 (GRCm39) missense probably damaging 0.98
R7021:Slc4a4 UTSW 5 89,188,205 (GRCm39) splice site probably null
R7180:Slc4a4 UTSW 5 89,194,095 (GRCm39) missense probably damaging 0.97
R7197:Slc4a4 UTSW 5 89,082,433 (GRCm39) intron probably benign
R7246:Slc4a4 UTSW 5 89,270,262 (GRCm39) missense probably damaging 0.99
R7309:Slc4a4 UTSW 5 89,318,610 (GRCm39) missense probably benign
R7412:Slc4a4 UTSW 5 89,362,506 (GRCm39) splice site probably null
R7492:Slc4a4 UTSW 5 89,277,509 (GRCm39) missense possibly damaging 0.92
R7561:Slc4a4 UTSW 5 89,347,556 (GRCm39) missense probably damaging 1.00
R7577:Slc4a4 UTSW 5 89,373,726 (GRCm39) missense probably damaging 0.97
R7609:Slc4a4 UTSW 5 89,283,545 (GRCm39) missense probably damaging 1.00
R7781:Slc4a4 UTSW 5 89,376,791 (GRCm39) missense possibly damaging 0.78
R7931:Slc4a4 UTSW 5 89,318,640 (GRCm39) missense probably benign 0.00
R7950:Slc4a4 UTSW 5 89,206,137 (GRCm39) splice site probably null
R8078:Slc4a4 UTSW 5 89,327,566 (GRCm39) missense probably benign 0.00
R8313:Slc4a4 UTSW 5 89,194,122 (GRCm39) missense possibly damaging 0.84
R8332:Slc4a4 UTSW 5 89,327,680 (GRCm39) missense probably benign 0.11
R8534:Slc4a4 UTSW 5 89,283,581 (GRCm39) missense probably damaging 1.00
R8735:Slc4a4 UTSW 5 89,280,301 (GRCm39) missense probably damaging 1.00
R8786:Slc4a4 UTSW 5 89,232,549 (GRCm39) missense probably benign 0.07
R8968:Slc4a4 UTSW 5 89,232,512 (GRCm39) missense probably benign
R9014:Slc4a4 UTSW 5 89,280,245 (GRCm39) missense probably damaging 1.00
R9031:Slc4a4 UTSW 5 89,205,568 (GRCm39) intron probably benign
R9195:Slc4a4 UTSW 5 89,281,055 (GRCm39) missense possibly damaging 0.82
R9236:Slc4a4 UTSW 5 89,194,158 (GRCm39) nonsense probably null
R9261:Slc4a4 UTSW 5 89,347,568 (GRCm39) missense probably damaging 1.00
R9401:Slc4a4 UTSW 5 89,327,525 (GRCm39) missense probably damaging 1.00
R9457:Slc4a4 UTSW 5 89,362,432 (GRCm39) missense probably damaging 1.00
R9462:Slc4a4 UTSW 5 89,194,131 (GRCm39) missense probably damaging 1.00
R9681:Slc4a4 UTSW 5 89,102,723 (GRCm39) nonsense probably null
R9709:Slc4a4 UTSW 5 89,188,205 (GRCm39) splice site probably null
Z1177:Slc4a4 UTSW 5 89,280,318 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- TACCTGTAAGGATTTCTGCTGG -3'
(R):5'- TCAGATGATCCTCTGGAGCC -3'

Sequencing Primer
(F):5'- AAGGATTTCTGCTGGGGTTCTAGC -3'
(R):5'- AGATGATCCTCTGGAGCCTTCAG -3'
Posted On 2022-04-18