Mutagenetix > Incidental Mutation

Incidental Mutation 'R5888:Slc4a1'

457818

Institutional Source

Beutler Lab

Gene Symbol

Slc4a1

Ensembl Gene

ENSMUSG00000006574

Gene Name

solute carrier family 4 (anion exchanger), member 1

Synonyms

Ae1, CD233, l11Jus51, band 3, Empb3, erythrocyte membrane protein band 3

MMRRC Submission

044089-MU

Accession Numbers

Genbank: NM_011403; MGI: 109393

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R5888 (G1)

Quality Score

203

Status

Validated

Chromosome

Chromosomal Location

102348824-102366203 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 102356525 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Valine at position 448 (E448V)

Ref Sequence

ENSEMBL: ENSMUSP00000006749 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000006749]

AlphaFold

P04919

Predicted Effect

probably damaging
Transcript: ENSMUST00000006749
AA Change: E448V

PolyPhen 2 Score 0.984 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000006749
Gene: ENSMUSG00000006574
AA Change: E448V

Domain	Start	End	E-Value	Type
low complexity region	58	68	N/A	INTRINSIC
Pfam:Band_3_cyto	100	342	1.6e-81	PFAM
Pfam:HCO3_cotransp	391	584	5.7e-85	PFAM
Pfam:HCO3_cotransp	575	857	5.6e-118	PFAM
transmembrane domain	875	892	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000128405

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000145636

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000149993

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000151050

Meta Mutation Damage Score

0.5867

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.2%
20x: 94.9%

Validation Efficiency

94% (96/102)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is part of the anion exchanger (AE) family and is expressed in the erythrocyte plasma membrane, where it functions as a chloride/bicarbonate exchanger involved in carbon dioxide transport from tissues to lungs. The protein comprises two domains that are structurally and functionally distinct. The N-terminal 40kDa domain is located in the cytoplasm and acts as an attachment site for the red cell skeleton by binding ankyrin. The glycosylated C-terminal membrane-associated domain contains 12-14 membrane spanning segments and carries out the stilbene disulphonate-sensitive exchange transport of anions. The cytoplasmic tail at the extreme C-terminus of the membrane domain binds carbonic anhydrase II. The encoded protein associates with the red cell membrane protein glycophorin A and this association promotes the correct folding and translocation of the exchanger. This protein is predominantly dimeric but forms tetramers in the presence of ankyrin. Many mutations in this gene are known in man, and these mutations can lead to two types of disease: destabilization of red cell membrane leading to hereditary spherocytosis, and defective kidney acid secretion leading to distal renal tubular acidosis. Other mutations that do not give rise to disease result in novel blood group antigens, which form the Diego blood group system. Southeast Asian ovalocytosis (SAO, Melanesian ovalocytosis) results from the heterozygous presence of a deletion in the encoded protein and is common in areas where Plasmodium falciparum malaria is endemic. One null mutation in this gene is known, resulting in very severe anemia and nephrocalcinosis. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes for null mutations exhibit retarded growth, severe spherocytosis, hemolytic anemia, lack of erythrocyte glycophorin A, mitotic defects, and high postnatal mortality. [provided by MGI curators]

Allele List at MGI

All alleles(6) : Targeted, knock-out(3) Targeted, other(1) Spontaneous(1) Chemically induced(1)

Other mutations in this stock

Total: 92 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700029P11Rik	T	C	15: 81,980,671	S38P	probably benign	Het
Adcy1	T	A	11: 7,139,095	V503E	possibly damaging	Het
Alk	C	A	17: 71,874,943	V1362L	probably damaging	Het
Ankrd55	T	A	13: 112,355,919	I208N	possibly damaging	Het
Asap2	T	A	12: 21,218,190	I319N	probably damaging	Het
Atp11b	T	C	3: 35,837,547	I1036T	probably benign	Het
B4gat1	T	C	19: 5,039,532	F186L	probably benign	Het
C3	T	A	17: 57,214,831	T1079S	probably damaging	Het
Cacul1	G	T	19: 60,537,464	T287K	possibly damaging	Het
Cbr3	G	C	16: 93,690,726	G266R	probably damaging	Het
Cd63	T	A	10: 128,912,291		probably null	Het
Chd7	G	A	4: 8,866,382	M851I	probably damaging	Het
Chst13	T	A	6: 90,309,572	H136L	probably benign	Het
Cyp2d22	T	C	15: 82,373,813	T179A	probably benign	Het
Dclre1b	A	T	3: 103,803,737	V286E	probably damaging	Het
Defb45	G	A	2: 152,593,234		probably benign	Het
Dlg1	T	C	16: 31,791,886		probably null	Het
Dock3	A	G	9: 107,023,803	V321A	probably benign	Het
Dytn	A	T	1: 63,677,237	V59E	possibly damaging	Het
Eif2ak1	A	G	5: 143,886,915	I393M	probably damaging	Het
Fam83g	A	T	11: 61,702,594	E318V	probably benign	Het
Fbxo34	T	A	14: 47,529,719	F179I	probably damaging	Het
Fmo5	T	A	3: 97,641,725	Y230N	probably benign	Het
Fzd9	T	G	5: 135,249,463		probably null	Het
Gata2	T	C	6: 88,200,740	S251P	probably benign	Het
Gigyf1	A	G	5: 137,525,697	D1043G	probably damaging	Het
Gm10260	G	A	13: 97,760,393	R66*	probably null	Het
Gm10322	T	A	10: 59,616,303	S81T	probably benign	Het
Gm11639	T	C	11: 104,721,401		probably benign	Het
Gm15517	A	T	7: 44,260,642		probably benign	Het
Haus4	T	C	14: 54,544,219	T232A	probably benign	Het
Hgfac	A	T	5: 35,045,407	H417L	probably damaging	Het
Iqgap2	T	C	13: 95,635,610	K1354E	possibly damaging	Het
Kcnk12	C	A	17: 87,746,649	R195L	probably benign	Het
Kcnn2	A	T	18: 45,592,345	I303F	probably damaging	Het
Kcnt1	T	C	2: 25,908,110	F879S	probably damaging	Het
Kndc1	T	C	7: 139,895,217	F11L	probably benign	Het
Kpna7	A	G	5: 144,989,795	F449S	probably damaging	Het
Krt77	G	T	15: 101,865,453	N255K	probably benign	Het
Lair1	A	T	7: 4,010,845	D134E	probably damaging	Het
Loxhd1	T	C	18: 77,402,515	V1318A	probably damaging	Het
March10	A	T	11: 105,402,146	V145D	possibly damaging	Het
Mcpt1	T	A	14: 56,019,512	M169K	probably benign	Het
Mdc1	T	A	17: 35,847,820	V364E	probably benign	Het
Mfsd11	T	C	11: 116,871,384	F270S	probably damaging	Het
Mfsd4b2	T	G	10: 39,922,035	D108A	probably benign	Het
Mink1	A	T	11: 70,610,059		probably benign	Het
Mmp25	T	C	17: 23,631,074	Y504C	probably damaging	Het
Ms4a13	C	T	19: 11,191,506	V52I	probably benign	Het
Msh4	C	T	3: 153,867,723		probably null	Het
Muc5b	T	G	7: 141,858,421	S1701R	unknown	Het
Naalad2	A	T	9: 18,330,641	S656T	probably benign	Het
Ncapd2	T	C	6: 125,187,089	Y64C	probably damaging	Het
Ncapg2	T	A	12: 116,425,800	S347T	possibly damaging	Het
Nipal4	T	C	11: 46,151,339	T172A	probably damaging	Het
Nrros	T	C	16: 32,143,087	K652R	probably benign	Het
Nrxn3	G	T	12: 89,512,085	A983S	possibly damaging	Het
Olfr1084	A	C	2: 86,639,144	L188R	probably damaging	Het
Olfr1187-ps1	T	C	2: 88,540,244		noncoding transcript	Het
Olfr1220	T	A	2: 89,097,925	M1L	probably damaging	Het
Olfr1249	T	A	2: 89,630,799	Y33F	probably damaging	Het
Olfr1283	T	C	2: 111,368,743	M37T	probably benign	Het
Olfr631	A	G	7: 103,929,032	T70A	possibly damaging	Het
Olfr938	A	T	9: 39,077,967	Y259*	probably null	Het
P2rx4	T	A	5: 122,719,165	S155T	probably benign	Het
P2rx4	T	G	5: 122,727,208	Y299D	probably damaging	Het
Pcsk6	A	T	7: 66,043,624	L7F	probably null	Het
Pdss2	T	C	10: 43,221,797		silent	Het
Pfkl	A	G	10: 77,991,370	V494A	possibly damaging	Het
Prep	G	T	10: 45,067,364	D12Y	possibly damaging	Het
Prg4	A	G	1: 150,452,350	F188S	probably damaging	Het
Ripor3	T	C	2: 167,997,287	Y98C	probably damaging	Het
Rnf216	T	A	5: 143,068,314		probably null	Het
Rnf24	A	G	2: 131,322,245		probably benign	Het
Scn3a	A	G	2: 65,497,398	M916T	probably benign	Het
Scnm1	T	C	3: 95,130,285	I157V	probably benign	Het
Sh2b3	C	G	5: 121,829,021	R10P	possibly damaging	Het
Slc25a27	T	C	17: 43,649,694	D211G	probably damaging	Het
Slc36a4	A	T	9: 15,727,028	Y250F	probably damaging	Het
Slit1	C	A	19: 41,743,296	C38F	probably damaging	Het
Spock3	T	A	8: 63,355,300	N410K	unknown	Het
Supt20	G	T	3: 54,712,207	W370L	probably benign	Het
Tas2r139	T	A	6: 42,141,496	N187K	probably damaging	Het
Tbc1d9b	G	A	11: 50,140,484	V111I	probably benign	Het
Thsd7b	T	A	1: 130,210,320	Y1578*	probably null	Het
Tln2	T	A	9: 67,229,403	I1267F	probably damaging	Het
Tnk2	G	A	16: 32,671,367	V363I	probably damaging	Het
Ttc32	A	G	12: 9,035,870	K139R	possibly damaging	Het
Vmn1r30	G	C	6: 58,435,565	T94S	possibly damaging	Het
Vmn1r90	G	A	7: 14,561,855	T106I	probably damaging	Het
Zfp677	T	A	17: 21,398,258	C526S	probably damaging	Het
Zfp831	T	G	2: 174,643,627	S32A	probably benign	Het

Other mutations in Slc4a1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01303:Slc4a1	APN	11	102357964	missense	probably benign	0.09
IGL01845:Slc4a1	APN	11	102353903	missense	probably benign	0.01
IGL02166:Slc4a1	APN	11	102354333	missense	probably damaging	1.00
IGL02745:Slc4a1	APN	11	102356267	missense	probably damaging	1.00
IGL02801:Slc4a1	APN	11	102359146	critical splice acceptor site	probably null
Rumor	UTSW	11	102361222	nonsense	probably null
A5278:Slc4a1	UTSW	11	102353815	splice site	probably benign
R0011:Slc4a1	UTSW	11	102357110	missense	possibly damaging	0.51
R0193:Slc4a1	UTSW	11	102352684	missense	possibly damaging	0.91
R0445:Slc4a1	UTSW	11	102354366	missense	probably benign	0.04
R0599:Slc4a1	UTSW	11	102357915	splice site	probably benign
R0635:Slc4a1	UTSW	11	102352672	missense	possibly damaging	0.78
R1496:Slc4a1	UTSW	11	102361171	missense	probably benign
R1816:Slc4a1	UTSW	11	102351230	missense	probably damaging	1.00
R1898:Slc4a1	UTSW	11	102350307	missense	probably damaging	1.00
R2361:Slc4a1	UTSW	11	102356830	missense	probably damaging	1.00
R2381:Slc4a1	UTSW	11	102359302	missense	probably benign	0.00
R3806:Slc4a1	UTSW	11	102357193	missense	probably benign	0.00
R3857:Slc4a1	UTSW	11	102357121	missense	probably benign	0.01
R3858:Slc4a1	UTSW	11	102357121	missense	probably benign	0.01
R4585:Slc4a1	UTSW	11	102361419	utr 5 prime	probably benign
R4586:Slc4a1	UTSW	11	102361419	utr 5 prime	probably benign
R4705:Slc4a1	UTSW	11	102356258	missense	possibly damaging	0.89
R4914:Slc4a1	UTSW	11	102352453	missense	probably damaging	1.00
R4915:Slc4a1	UTSW	11	102352453	missense	probably damaging	1.00
R4916:Slc4a1	UTSW	11	102352453	missense	probably damaging	1.00
R4918:Slc4a1	UTSW	11	102352453	missense	probably damaging	1.00
R5001:Slc4a1	UTSW	11	102351503	missense	probably benign	0.12
R5103:Slc4a1	UTSW	11	102353261	missense	possibly damaging	0.65
R5234:Slc4a1	UTSW	11	102361383	missense	probably benign	0.03
R5308:Slc4a1	UTSW	11	102359077	missense	probably damaging	0.98
R5315:Slc4a1	UTSW	11	102358254	missense	possibly damaging	0.77
R5478:Slc4a1	UTSW	11	102350314	missense	probably damaging	0.98
R5521:Slc4a1	UTSW	11	102353266	missense	probably benign	0.01
R6011:Slc4a1	UTSW	11	102352531	missense	probably damaging	1.00
R6547:Slc4a1	UTSW	11	102356735	missense	probably damaging	0.99
R6629:Slc4a1	UTSW	11	102361222	nonsense	probably null
R6717:Slc4a1	UTSW	11	102354423	missense	probably damaging	0.99
R7051:Slc4a1	UTSW	11	102356258	missense	probably benign	0.12
R7103:Slc4a1	UTSW	11	102353867	missense	probably damaging	0.97
R7315:Slc4a1	UTSW	11	102356484	missense	probably damaging	1.00
R7331:Slc4a1	UTSW	11	102361419	start gained	probably benign
R7582:Slc4a1	UTSW	11	102352577	missense	probably damaging	0.99
R8560:Slc4a1	UTSW	11	102353257	missense	possibly damaging	0.94
R9036:Slc4a1	UTSW	11	102352453	missense	probably damaging	1.00
R9274:Slc4a1	UTSW	11	102351221	missense	probably benign	0.00
R9502:Slc4a1	UTSW	11	102356848	missense	probably damaging	0.97
R9568:Slc4a1	UTSW	11	102356854	missense	probably damaging	1.00
R9585:Slc4a1	UTSW	11	102357089	missense	probably benign	0.08
R9651:Slc4a1	UTSW	11	102351430	missense	probably damaging	1.00
RF006:Slc4a1	UTSW	11	102356716	critical splice donor site	probably null

Predicted Primers

PCR Primer
(F):5'- GGTGAGCCAGGGTAAACTAC -3'
(R):5'- TCCTGGGTCAGTGACAATTATG -3'

Sequencing Primer
(F):5'- TAAACTACAGGGTTGGGGGTC -3'
(R):5'- GGTCAGTGACAATTATGGTTCTCCC -3'

Posted On

2017-02-15